Microbiology, Usmle Endpoint

USMLE ENDPOINT Dr Ahmed Shebl
Basic bacteriology
Bacterial structures:
STRUCTURE CHEMICAL COMPOSITION FUNCTION

Appendages
Flagellum  Proteins.  Motility.
UW: flagellar (H) antigen is a
heat labile protein, which is one
component of serologic
classification of the
enterobacteriaceae.
Pilus/fimbria  Glycoprotein.  Mediate adherence of
 Shorter than flagella and do not bacteria to cell surface.
move.  Sex pilus forms during
conjugation.
Specialized structures
Spore  Keratin-like coat; dipicolinic  Gram ⊕ only.
acid; peptidoglycan, DNA.  Survival: resist dehydration,
heat, chemicals.
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Cell envelope
Capsule  Organized, discrete  Protects against

polysaccharide layer (except phagocytosis.
poly-d-glutamate on B
anthracis).
Glycocalyx  Loose network of  Mediates adherence to
polysaccharides. surfaces, especially foreign
surfaces (eg, indwelling
catheters).
Outer  Outer leaflet: contains:  Gram ⊝ only.
membrane  Endotoxin (LPS/LOS).  Endotoxin:
 Embedded proteins: porins  Lipid A induces TNF and
(allow passage of nutrients). IL-1.
 Outer membrane proteins  Antigenic O
(OMPs). polysaccharide
 Inner leaflet: phospholipids. component.
 Most OMPs are antigenic.
 Porins: transport across outer
membrane.
Periplasm  Space between cytoplasmic  Accumulates components
membrane and outer membrane exiting gram ⊝ cells,
in gram ⊝ bacteria. including hydrolytic
(Peptidoglycan in middle.) enzymes (eg, β-lactamases).
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Cell wall  Peptidoglycan is a sugar  Net-like structure gives rigid

backbone with peptide side support, protects against
chains cross-linked by osmotic pressure damage.
transpeptidase.  Transpeptidase is located in
 The gram-positive cell wall is the inner cytoplasmic
very thick and has extensive membrane. The antibiotic
cross-linking of the amino-acid penicillin binds to and
side chains. In contrast, the inhibits this enzyme. For this
gram-negative cell wall is very reason the enzyme is also
thin with a fairly simple cross- called penicillin binding
linking pattern. protein.
Cytoplasmic  Phospholipid bilayer sac with  Site of oxidative and transport
membrane embedded proteins (eg, enzymes; PBPs
penicillin-binding proteins (transpeptidase) involved in
[PBPs]) and other enzymes. cell wall synthesis.
 Lipoteichoic acids (gram ⊕  Lipoteichoic acids induce
only) extend from membrane to TNF-α and IL-1.
exterior.  UW: teichoic acid serves as
antigenic determinent for
organism detection and
antigenic target for the
human immune system.
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Cell walls:
 UW: Bacterial sepsis is caused by:

 In case of gram –ve bacteria:
 Endotoxin
 In case of gram +ve bacteria:
 Cell wall component (including peptidoglycans and lipoteichoic
acid).
 Exotoxin.
 UW: Penicillins, cephalosporins and vancomycin are able to disrupt the
peptidoglycan cell wall of Gram-positive and Gram-negative organisms. The
peptidoglycan cell wall of these organisms gives them the ability to survive osmotic
stress this ability is lost after treatment with these antibiotic agents.
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Bacterial taxonomy
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Stains
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Properties of growth media

 The same type of media can possess both (or neither) of these properties.
Selective media
 Favors the growth of particular organism while preventing growth of other organisms.
 eg, Thayer Martin agar contains antibiotics that allow the selective growth of Neisseria
by inhibiting the growth of other sensitive organisms.
Indicator (differential) media

 Yields a color change in response to the metabolism of certain organisms.
 eg, MacConkey agar contains a pH indicator; a lactose fermenter like E coli will convert
lactose to acidic metabolites  color change.
Enrichment media
 Contain special growth factors required by some organisms to grow.
 Eg, the X and V factors required by Haemophilus or the anaerobic conditions needed by
Closthdium species.
Special culture requirements
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Aerobes
 Use an O2-dependent system to generate ATP.
 Examples include Nocardia, Pseudomonasaeruginosa, and MycoBacterium tuberculosis.
Nagging Pests Must Breathe.
 Reactivation of M tuberculosis (eg, after immunocompromise or TNF-α inhibitor use)
has a predilection for the apices of the lung.
Anaerobes
 Examples include Clostridium, Bacteroides, Fusobacterium, and Actinomyces.
Anaerobes Can’t Breathe Fresh Air.
 They lack catalase and/or superoxide dismutase and are thus susceptible to oxidative
damage.
 Generally foul smelling (short-chain fatty acids), are difficult to culture, and produce gas
in tissue (CO2 and H2).
 Anaerobes are normal flora in GI tract, typically pathogenic elsewhere.
 AminO2glycosides are ineffective against anaerobes because these antibiotics require O2
to enter into bacterial cell.
Facultative anaerobes
 Use fermentation and other nonoxygen dependent pathways to generate ATP but are not
killed by O2.
 Streptococci, staphylococci, and enteric gram ⊕ bacteria.
Intracellular bugs
Obligate intracellular
 Rickettsia, CHlamydia, COxiella. Rely on host ATP.
 Stay inside (cells) when it is Really CHilly and COld.
Facultative intracellular
 Salmonella, Neisseria, Brucella, Mycobacterium, Listeria, Francisella, Legionella,
Yersinia pestis.
 Some Nasty Bugs May Live FacultativeLY.
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Encapsulated bacteria
 Examples: (Please SHINE my SKiS.)
 Pseudomonas aeruginosa, Streptococcus
pneumoniae A, Haemophilus Influenzae type B,
Neisseria meningitidis, Escherichia coli,
Salmonella, Klebsiella pneumoniae, and group
B Strep.
 Function of the capsule:
 Antiphagocytic virulence factor.
 Opsonins (C3b, IgG) enhance phagocytosis, and
then cleared by spleen:
 Asplenics have ↓ opsonizing ability and
thus ↑ risk for severe infections.
 Give S pneumoniae, H influenzae, N
meningitidis vaccines.
 Stain:
 Two important tests enable doctors to visualize
capsules under the microscope and aid in
identifying bacteria:
 India ink stain: Because this stain is not
taken up by the capsule, the capsule
appears as a transparent halo around the
cell. This test is used primarily to
identify the fungus Cryptococcus.
 Quellung reaction: The bacteria are
mixed with antibodies that bind to the
capsule. When these antibodies bind, the
capsule swells with water, and this can
be visualized microscopically.
Encapsulated bacteria vaccines

 Some vaccines containing polysaccharide capsule
antigens are conjugated to a carrier protein, enhancing immunogenicity by promoting T-
cell activation and subsequent class switching.
 A polysaccharide antigen alone cannot be presented to T cells.
 Pneumococcal vaccine:
 PCV13 (pneumococcal conjugate vaccine).
 PPSV23 (pneumococcal polysaccharide vaccine with no conjugated protein).
 H influenzae type B (conjugate vaccine)
 Meningococcal vaccine (conjugate vaccine)
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Urease-positive organisms
 Proteus, Cryptococcus, H pylori, Ureaplasma, Nocardia, Klebsiella, S epidermidis, S
saprophyticus. Pee CHUNKSS.
 Urease hydrolyzes urea to release ammonia and CO2  ↑ pH.
 Predisposes to struvite (ammonium magnesium phosphate) stones, particularly Proteus.
Catalase-positive organisms
 Catalase degrades H2O2 into H2O and bubbles of O2 A before
it can be converted to microbicidal products by the enzyme
myeloperoxidase.
 People with chronic granulomatous disease (NADPH
oxidase deficiency) have recurrent infections with certain
catalase ⊕ organisms.
 Examples: Nocardia, Pseudomonas, Listeria, Aspergillus,
Candida, E coli, Staphylococci, Serratia, B cepacia, H pylori.
(Cats Need PLACESS to Belch their Hairballs.)
Pigment-producing bacteria
 Actinomyces israelii—yellow ―sulfur‖ granules, which are composed of filaments of
bacteria. Israel has yellow sand.
 S aureus—yellow pigment. Aureus (Latin) = gold.
 P aeruginosa—blue-green pigment (pyocyanin and pyoverdin). Aerugula is green.
 Serratia marcescens—red pigment. Serratia marcescens—think red maraschino
cherries.
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In vivo biofilm producing bacteria

 S epidermidis Catheter and prosthetic device infections.
 Viridans streptococci (S mutans, S sanguinis)  Dental plaques, infective
endocarditis.
 P aeruginosa  Respiratory tree colonization in patients with cystic fibrosis, ventilator-
associated pneumonia. Contact lens–associated keratitis.
 Nontypeable (unencapsulated) H influenzae  Otitis media.
Bacterial virulence factors

 These promote evasion of host immune response.
Protein A
 Binds Fc region of IgG.
 Prevents opsonization and phagocytosis.
 Expressed by S aureus.
IgA protease
 Enzyme that cleaves IgA, allowing bacteria to adhere to and colonize mucous
membranes.
 Secreted by S pneumoniae, H influenzae type B, and Neisseria (SHiN).
M protein
 Helps prevent phagocytosis.
 Expressed by group A streptococci.
 Shares similar epitopes to human cellular proteins (molecular mimicry); possibly
underlies the autoimmune response seen in acute rheumatic fever.
Type III secretion system

 Also known as ―injectisome.‖
 Needle-like protein appendage facilitating direct delivery of toxins from certain gram ⊝
bacteria (eg, Pseudomonas, Salmonella, Shigella, E coli) to eukaryotic host cell.
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Bacterial genetics
Transformation
 Competent bacteria are able to bind and import short pieces of environmental naked
bacterial chromosomal DNA (from bacterial cell lysis).
 The transfer and expression of newly transferred genes is called transformation.
 A feature of many bacteria, especially S pneumoniae, H influenzae type B, and Neisseria
(SHiN).
 Any DNA can be used.
 Adding deoxyribonuclease to environment will degrade naked DNA in medium  no
transformation seen.
Conjugation
F+ × F-
 F+ plasmid contains genes required for sex pilus and conjugation.
 Bacteria without this plasmid are termed F–.
 Sex pilus on F+ bacterium contacts F- bacterium.
 A single strand of plasmid DNA is transferred across the conjugal bridge (―mating
bridge‖).
 No transfer of chromosomal DNA.
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Hfr × F-
 F+ plasmid can become incorporated into bacterial chromosomal DNA, termed high
frequency recombination (Hfr) cell.
 Transfer of leading part of plasmid and a few flanking chromosomal genes.
 High-frequency recombination may integrate some of those bacterial genes.
 The recipient cell remains F– but now may have new bacterial genes.
Transduction
A- Generalized transduction
 A ―packaging‖ event.
 Lytic phage (virulent phage) infects bacterium, leading to cleavage of bacterial DNA.
 Parts of bacterial chromosomal DNA may become packaged in phage capsid.
 Phage infects another bacterium, transferring these genes.
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B- Specialized transduction
 An ―excision‖ event.
 Lysogenic phage (temperate phage) infects bacterium; viral DNA incorporates into
bacterial chromosome.
 When phage DNA is excised, flanking bacterial genes may be excised with it.
 DNA is packaged into phage capsid and can infect another bacterium.
 Genes for the following 5 bacterial toxins are encoded in a lysogenic phage (ABCD’S):
Group A strep erythrogenic toxin, Botulinum toxin, Cholera toxin, Diphtheria toxin,
Shiga toxin.
Transposition
 Segment of DNA (eg, transposon) that can ―jump‖ (excision and reintegration) from one
location to another can transfer genes from plasmid to chromosome and vice versa.
 When excision occurs, may include some flanking chromosomal DNA, which can be
incorporated into a plasmid and transferred to another bacterium (eg, vanA gene from
vancomycin-resistant Enterococcus to S aureus).
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Spore-forming bacteria
 Some bacteria can form spores A at the end of the stationary phase when nutrients are
limited.
 Spores are highly resistant to heat and chemicals.
 Have dipicolinic acid in their core.
 Have no metabolic activity.
 Must autoclave to potentially kill spores (as is done to surgical equipment) by steaming
at 121°C for 15 minutes.
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Main features of exotoxins and endotoxins
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Bugs with exotoxins
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Endotoxin
 LPS found in outer membrane of gram ⊝ bacteria (both
cocci and rods).
 LPS is composed of:
 O antigen (Oligosaccharides). (Outer
membrane)
 Core polysaccharide.
 Lipid A (the toxic component) =
endotoxin.
 Released upon cell lysis or by
living cells by blebs
detaching from outer surface
membrane (vs exotoxin,
which is actively secreted).
 Three main effects of the endotoxin:
 Macrophage activation (TLR4).
 Complement activation.
 Tissue factor activation.
 All gram +ve bacteria don’t have endotoxin except Listeria.
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Clinical microbiology:
Gram-positive lab algorithm
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Gram-positive cocci antibiotic tests
α-Hemolytic bacteria
 Gram ⊕ cocci.
 Partial reduction of hemoglobin causes greenish or brownish
color without clearing around growth on blood agar A.
 Include the following organisms:
 Streptococcus pneumoniae (catalase ⊝ and optochin
sensitive).
 Viridans streptococci (catalase ⊝ and optochin resistant).
β-hemolytic bacteria
 Gram ⊕ cocci.
 Complete lysis of RBCs  clear area surrounding colony on
blood agar A.
 Include the following organisms:
 Staphylococcus aureus (catalase and coagulase ⊕)
 Streptococcus pyogenes—group A strep (catalase ⊝ and
bacitracin sensitive)
 Streptococcus agalactiae—group B strep (catalase ⊝ and bacitracin resistant)
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Staphylococcus aureus
 Lab:
1. Gram ⊕, β-hemolytic, catalase ⊕, coagulase ⊕ cocci in clusters.
2. Small yellow colonies on blood agar.
3. Ferments mannitol (turns pink to yellow, contrast other Staph).
 Virulence:
1. Protein A (virulence factor)
 Binds Fc-IgG, inhibiting complement activation and phagocytosis.
 Forms part of the outer peptidoglycan layer of S aureus.
 Diseases: (Commonly colonizes the nares, axilla, and groin.)
1. Inflammatory disease:
 Coagulase  forms fibrin clot around self  abscess.
 Pneumonia (often after influenza virus infection).
 Endocarditis (IV drug abuse).
 Septic arthritis, and osteomyelitis.
 Surgical Infections: presents with erythema, pain/tenderness at surgical
site, fever.
 Suppurative parotitis.
 Hepatic abscess via hematogenous seeding.
2. Toxin-mediated disease:
 Toxic shock syndrome (TSST-1)
 TSST-1 is a superantigen that binds to MHC II and T-cell
receptor, resulting in polyclonal T-cell activation.
 Associated with prolonged use of vaginal tampons or nasal
packing.
 Presents with fever, vomiting, rash, desquamation, shock, end-
organ failure.
 Desquamation particularly on the palms and soles, can occur 1-2
weeks after the onset of illness.
 TSS results in ↑ AST, ↑ ALT, ↑ bilirubin.
 Compare with Streptococcus pyogenes TSS (a toxic shock–like
syndrome associated with painful skin infection).
 Scalded skin syndrome (exfoliative toxin). (SSSS)
 Epidermolytic toxins A and B against desmoglein-1 in stratum
granulosum.
o Bullous impetigo is a more localized form of SSSS with the
bulla formation being another effect of exfoliative toxin.
 Nikolsky's sign (skin slipping off with gentle pressure.)
 Pain associated with the skin rash.
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 Rapid-onset food poisoning (enterotoxins).

 Due to ingestion of preformed toxin  short incubation period (2–
6 hr) followed by nonbloody diarrhea, emesis, and cramping.
 Enterotoxin is heat stable  not destroyed by cooking.
 Because this is a preformed exotoxin, there is no person-to-
person transmission, but outbreaks can occur with many people
eating the same contaminated food.
 The most frequently tested food item is a mayonnaise-containing
food like potato or macaroni salad.
3. MRSA (methicillin-resistant S aureus) infection:

 Important cause of serious nosocomial and community-acquired
infections.
 Resistant to methicillin and nafcillin because of altered penicillin-
binding protein.
 Treat with Vancomycin, Clindamycin, TMP-SMX.
4. VRSA (Vancomycin resistant s aureus) infection:
 Treat with Quinupristin, Dalfopristin.
 UW: S aureus is the most common cause of tricuspid endocarditis in intravenous

drug users.
 Pseudomonas aeruginosa is the second most common cause in this patient
population.
 These patients can develop multiple septic emboli in lungs.
 Pulmonary infarcts are almost always hemorrhagic due to the dual blood supply
to the lungs (pulmonary and bronchial arteries).
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 UW: MRSA:
 S aureus strains that are resistant to oxacillin, nafcillin, and methicillin have been
historically termed MRSA, but they are also resistant to all (beta-lactam agents,
including penicillin, cephalosponns (except ceftaroline; a fifth-generation cephalosporin),
and carbapenems.
 Methicillin (nafcillin) resistance is typically mediated by alterations in the structure of
penicillin-binding proteins (PBP), the enzymes involved in cell wall synthesis.
 Altered PBPs have greatly reduced affinity for beta-lactam antimicrobial agents (except
ceftaroline).
UW: Secondary bacterial pneumonia after influenza A virus:
 Patients older than 65 are particularly prone.

 Characterized by recurrent fever, dyspnea, productive cough, and lung consolidation in CXR.
 Because of virally-induced damage to the mucociliary clearance mechanisms of the
respiratory epithelium.
 In order, the pathogens most often responsible for secondary bacterial pneumonia are
Streptococcus pneumonia, Staphylococcus aureus, and Haemophilus influenzae.
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Staphylococcus epidermidis
 Lab:
 Gram ⊕, catalase ⊕, coagulase ⊝, urease ⊕ cocci in clusters.
 Novobiocin sensitive. Does not ferment mannitol (vs S aureus).
 Normal flora of skin; contaminates blood cultures.
 Diseases:
 Produce adherent biofilm  infects prosthetic devices (eg, hip implant, heart
valve) and IV catheters. Most common cause of endocarditis in patients with
artificial valves.
 Presents with erythema at entry site.
 Treat with Vancomycin, replacement of infected devices.
Initial empiric treatment of coagulase-negative

staphylococcal infection should include vancomycin
due to widespread methicillin resistance especially in
nosocomial infections.
If susceptibility results indicate a methicillin-

susceptible isolate, vancomycin can be switched to
nafcillin or oxacillin.
Staphylococcus saprophyticus
 Lab:
 Gram ⊕, catalase ⊕, coagulase ⊝, urease ⊕ cocci in clusters. Novobiocin
resistant.
 Normal flora of female genital tract and perineum.
 Diseases:
 Second most common cause of uncomplicated UTI in sexually active young
women (most common is E coli).
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Streptococcus pneumonia
 Lab:
1. Gram ⊕, lancet-shaped diplococcic.
2. α-hemolytic, optochin sensitive.
 Virulence:
3. Polysaccharide capsule: no virulence without capsule.
4. IgA protease: allows for invasion and colonization of mucosa.
5. Pneumolysin O: damages respiratory epithelium.
6. Peptidoglycan and Teichoic Acids: cause virulence in meningitis.
 Diseases: Most common cause of: (MOPSS)
1. Meningitis (in adults).
2. Otitis media (in children).
3. Bacterial pneumonia: lobar pneumonia that produces rusty-colored sputum.
4. Sinusitis.
5. Sepsis in patients with sickle cell disease, and asplenic patients.
 Vaccines:
1. Adult: Pneumococcal Polysaccharide Vaccine (PPV), 23-valent polysaccharide,
T-cell independent, IgM only.
2. Pediatric: Pneumococcal Capsular Vaccine (PCV), 7-valent conjugated to a
protein, T-cell response, IgG.
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Viridans group streptococci

 Lab:
1. Gram ⊕, α-hemolytic cocci.
2. Resistant to optochin:
 Differentiating them from S pneumoniae, which is α-hemolytic but is
optochin sensitive.
 Viridans group strep live in the mouth because they are not afraid of-the-
chin (op-to-chin resistant).
 Virulence:
1. Biofilm production  can adhere to tooth enamel and to fibrin-platelet
aggregates on damaged heart valves due to their ability to produce insoluble
extracellular polysaccharides (dextrans) using sucrose as a substrate.
 Diseases:
1. Dental Caries: (S. mutans/mitis)
 They are normal flora of the oropharynx.
 Biofilms form plaque.
2. Subacute bacterial endocarditis at damaged heart valves (S sanguinis).
 S sanguinis makes dextrans, which bind to fibrin-platelet aggregates on
damaged heart valves.
Streptococcus pyogenes (group A streptococci)

 Lab:
 Gram ⊕ cocci in chains. catalase⊖, β-hemolytic,
 PYR⊕ (pyrrolidonyl arylamidase, compare Enterococcus, contrast Strep bovis),
bacitracin sensitive (contrast Group B Strep), facultative aerobe.
 Virulence:
 Evasion:
 M Protein: main virulence factor, inhibits phagocytosis and complement
activation, mediates bacterial attachment, antibodies against it enhance
host defenses, but may cause Rheumatic Fever.
 Hyaluronic Acid Capsule: non-immunogenic, inhibits phagocytosis.
 Streptolysin O: immunogenic, lyses RBCs and PMNs.
 Streptolysin S: nonimmunogenic, lyses RBCs and PMNs.
 Invasion:
 Streptodornase: (DNase) degrades DNA in pus to facilitate spread of the
organism.
 Anti DNase can be used as a laboratory test in patients who have
had streptococcal infection followed by glomerulonephritis.
 Streptokinase: dissolves clot, converts plasminogen to plasmin by
phosphorylating it, plasmin is fibrinolytic.
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 Hyaluronidase: spreads rapidly to the deep layers of the skin and fascia.
 Adhesion:
 Protein F.
 TOXIN:
 Pyrogenic Exotoxins:
 SpeA and SpeC are superantigens causing TSLS.
 SpeB is a protease causing necrotizing fasciitis.
 Lipoteichoic Acid.
 Diseases:
 Pyogenic—pharyngitis, cellulitis, impetigo (―honey-crusted‖ lesions), erysipelas.
 Toxigenic—scarlet fever, toxic shock–like syndrome, necrotizing fasciitis.
 .Scarlet fever—blanching, sandpaper-like body rash, strawberry tongue,
and circumoral pallor in the setting of group A streptococcal pharyngitis
(erythrogenic toxin ⊕).
 Immunologic
 Rheumatic fever: (type II hypersensitivity)
 M protein antibodies cross react with myosin (molecular mimicry).
 Occurs after Strep pharyngitis but NOT after skin infection.
 Common in children with poor access to health care.
 J♥NES (major criteria for acute rheumatic fever):
Joints—polyarthritis, ♥—carditis, Nodules (subcutaneous),
Erythema marginatum, Sydenham chorea, Pharyngitis can result in
rheumatic ―phever‖ and glomerulonephritis.
 Histology:
o Aschoff body: Interstitial myocardial granuloma,
pathognomonic, contains plump macrophages with
abundant cytoplasm, central, slender, chromatin ribbons
(Anitschkow or ―caterpillar‖ cells).
 Preventable with early treatment.
 Glomerulonephritis (APSGN): (type III hypersensitivity)
 Occurs 2 weeks after either pharyngitis or impetigo (more
common).
 Note that while Staph aureus also causes impetigo, it does not lead
to PSGN.
 Increased age at onset the worst prognostic factor.
 Not preventable.
 Diagnosis:
 ASO titer or anti-DNase B antibodies indicate recent S pyogenes infection.
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Impetigo is caused by Staph

aureus and less commonly by
Strept pyogenes (Group A
streptococci [GAS]).
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Streptococcus agalactiae (group B streptococci)

 Lab:
 Gram ⊕ cocci, bacitracin resistant, β-hemolytic.
 Produces CAMP factor, which enlarges the area of hemolysis formed by S
aureus. (Note: CAMP stands for the authors of the test, not cyclic AMP.)
 Hippurate test ⊕. PYR ⊝.
 Diseases:
 Causes pneumonia, meningitis, and sepsis, mainly in babies. Group B for Babies!
 Colonizes vagina  screen pregnant women at 35–37 weeks of gestation with
rectal + vaginal swabs.
 Patients with ⊕ culture receive intrapartum penicillin prophylaxis.
Streptococcus bovis
 Gram ⊕ cocci, colonizes the gut.
 S gallolyticus (S bovis biotype 1) can cause bacteremia and subacute endocarditis and is
associated with colon cancer.
 Bovis in the blood = cancer in the colon.
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Enterococci
 Lab:
1. Gram ⊕ cocci. Catalase ⊝, PYR ⊕, variable hemolysis (alpha or gamma
hemolysis).
2. Bile resistant (grows in bile, bile esculin agar turns black.)
3. Grows in 6.5% NaCl (in contrast to Strep bovis).
 Diseases: Enterococci (E faecalis and E faecium) are normal colonic flora that are
penicillin G resistant.
1. UTI, biliary tract infections.
2. Subacute endocarditis (following GI/GU procedures).
 Eg, endocarditis after cystoscopy or colonoscopy or obstetric procedures.
3. VRE (vancomycin-resistant enterococci) are an important cause of nosocomial
infection.
 Due to alteration of D-Ala-D-Ala to D-Ala-D-Lac in cell wall precursors
by bacterial proteins acting as ligases.
 Resistance acquired via plasmids or transposons.
 Treat with Linezolid, Tigecycline, Streptogramins (e.g,
Quinupristin/Dalfopristin).
Enterococci have both intrinsic (beta-lactams, macrolides, aminoglycosides, trimethoprim-

sulfamethoxazole) and acquired (vancomycin) resistance to antibiotics, making them important
nosocomial pathogens.
Bacillus anthracis
 Lab:
1. Gram ⊕, spore-forming rod that produces anthrax toxin.
2. Colonies show a halo of projections, sometimes referred to as ―medusa head‖
appearance.
 Virulence:
1. Capsule: the only bacterium with a polypeptide capsule (contains D-glutamate
instead of polysaccharide).
2. Anthrax Toxin: trimeric toxin composed of protective antigen edema factor, and lethal
factor.
 Protective antigen: functions to translocate both edema and lethal factor
into the cytosol.
 Lethal Factor: exotoxin, protease that cleaves MAP kinase, a signal
transduction protein that regulates cell growth, responsible for tissue
necrosis of black eschar.
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 Edema Factor: acts as adenylate cyclase, increases cAMP, causes fluid to

enter intracellular space leading to edema, which inhibits host defenses
and phagocytosis, responsible for edematous border of black eschar.
 Diseases:
1. Cutaneous anthrax:
 Transmitted by direct contact with infected animals. Goat hair is the most
commonly implicated exposure in contraction of anthrax.
 Painless papule surrounded by vesicles  ulcer with black eschar
(painless, necrotic)  uncommonly progresses to bacteremia and death.
2. Pulmonary Anthrax:
 Transmitted via inhalation of spores (―woolsorter’s disease‖).
 B anthracis spreads via lymphatics to the bloodstream and the organism
multiplies in the blood and tissue.
 Presents with flu-like symptoms with rapid progression to fever,
pulmonary hemorrhage, hemorrhagic mediastinitis (widened mediastinum
on chest x-ray), shock, and death (near 100% mortality).
 Prevention:
1. Acellular Vaccine Adsorbed (AVA – toxoid vaccine) available.
 Treatment:
1. Fluoroquinolones (Ciprofloxacin), Doxycycline.
2. Postexposure prophylaxis:
 Same as treatment antibiotics.
 Monoclonal antibodies if other therapies not tolerated.
34 Microbiology
Bacillus cereus
 Gram ⊕ rod.
 Causes food poisoning. (Reheated rice syndrome.)
 Spores survive cooking rice.
 Keeping rice warm results in germination of spores and enterotoxin formation.
 Caused by cereulide, a preformed toxin.
 Emetic type
 Usually seen with rice and pasta.
 Nausea and vomiting within 1–5 hr.
 Diarrheal type
 Causes watery, nonbloody diarrhea and GI pain within 8–18 hr.
 Similar to E. coli  increased cAMP leads to excretion of Cl- and osmotic
water loss.
Clostridia (with exotoxins)

 Gram ⊕, spore-forming, obligate anaerobic rods.
 ―Tennis racket‖ appearance.
C tetani
 Virulence: (tetanospasmin)
1) An exotoxin causing tetanus.
2) Travels to the CNS via retrograde axonal transport.
3) Protease that cleaves SNARE proteins for
neurotransmitters (as botulinum toxin).
4) Blocks release of inhibitory neurotransmitters,
GABA and glycine, from Renshaw cells in spinal
cord.
35 Microbiology
 Transmission:
1) Via trauma or puncture wounds, especially stepping on a nail or being cut with
barbed wire (requires low tissue oxygenation). Reservoir is soil.
2) Colonization of umbilical stump in neonates.
 Disease: (tetanus): (Tetanus is tetanic paralysis.)
1) Spastic paralysis, trismus (lockjaw), risus sardonicus (raised eyebrows and open
grin), opisthotonos (spasms of spinal extensors).
2) Neonatal tetanus:
 Due to introduction of C. tetani spores to the infant, generally from
unhygienic deliveries or cord care.
 Prevention: (Tetanus vaccine)
1) Toxoid vaccine; toxin conjugated to a protein. Killed vaccine.
2) Infants administered DTaP vaccine at 2 months old, boosters given every 10 years
in adults, during 3rd trimester of pregnancy to prevent neonatal tetanus, following
puncture wounds if immune status uncertain.
 Treatment:
1) Tetanus IG (TIG, antitoxin) to neutralize the toxin +/- vaccine booster.
2) Antibiotics (Metronidazole or Penicillin)
3) Diazepam (for muscle spasms), and wound debridement.
36 Microbiology
C. botulinum
 Botulinum toxin:
1) Heat-labile toxin that inhibits ACh release at the neuromuscular junction,
causing botulism.
 Local botox injections used to treat focal dystonia, achalasia, and muscle
spasms.
 Also used for cosmetic reduction of facial wrinkles.
 Disease: (Botulism)
1) Transmission:
 In adults, disease is caused by ingestion of preformed toxin in the canned
food.
 In babies, ingestion of spores (not the toxin) (eg, in honey) leads to
disease (floppy baby syndrome).
2) Symptoms of descending paralysis (the 4 D’s): Diplopia, Dysarthria, Dysphagia,
Dyspnea (nicotinic blockade) + symptoms of muscarinic blockade (dry mouth,
myedriasis).
 Botulinum is from bad bottles of food, juice, and honey (causes a
descending flaccid paralysis).
 In infant botulism, constipation usually precedes the characteristic signs
of neuromuscular paralysis by a few days or weeks. Other symptoms: mild
weakness, lethargy, and poor feeding.
3) Treat with antitoxin.
37 Microbiology
C. perfringens
 Virulence:
1) α toxin (lecithinase with a phospholipase c activity)
that can cause myonecrosis (gas gangrene A) and
hemolysis. Perfringens perforates a gangrenous leg.
2) Spores can survive in undercooked food; when
ingested, bacteria release
heat-labile enterotoxin  food poisoning.
 Diseases:
1) Gas gangrene:
 Presents with tight tissue, skin tightness, pallor, lack of bleeding, severe
pain, blisters or necrotic bullae, crepitation, foul odor, blebs or gas
bubbles, fever and tachycardia.
 C perfringens uses carbohydrates for energy. Its rapid metabolism of
muscle tissue carbohydrates produces significant amounts of gas, which
can be demonstrated radiographically by plain film x-ray or CT scan.
2) Late-onset food Poisoning:
 Due to reheated meat dishes, enterotoxin produced in intestines.
 Caused by a toxin formed when large quantities of clostridial spores are
ingested, in contrast to early-onset food poisoning caused by the
preformed toxins of Staph aureus and Bacillus cereus.
 Presents with transient diarrhea and abdominal pain.
 Note: new research suggests involvement in MS.
 Detection:
1) Nagler reaction
 Egg yolk agar with anti-α-toxin on half – blocks the action of the C.
perfringens α-toxin, but not the phospholipases of other Clostridium
species.
38 Microbiology
C. difficile
 Virulence:
1) Produces 2 toxins:
 Toxin A, an enterotoxin, binds to brush border of gut and alters fluid
secretion.
 Toxin B, a cytotoxin, disrupts cytoskeleton via actin depolymerization
 disruption of intercellular tight junctions leading to cell
rounding/retraction.
 Diseases: (pseudomembranous colitis B)
 Treatment of C. Difficile infection:

1) Oral metronidazole (typically for mild to moderate cases).
2) Oral vancomycin (typically for severe cases).
3) For recurrent cases, consider repeating prior regimen, fIdaxomicin, or fecal
microbiota transplant.
4) Fidaxomicin:
 A macrocyclic antibiotic (related to macrolides) that inhibits the sigma
subunit of RNA polymerase, leading to protein synthesis impairment and
cell death.
39 Microbiology
 It is an oral drug with bacteriocidal activity, minimal systemic absorption,

and a narrow spectrum; it has less effect on normal colonic flora than
either metronidazole or vancomycin.
UW: Tetrodotoxin poisoning (due to contaminated pufferfish ingestion) leads to inhibition

of sodium influx into nerve endings. Manifestations include weakness, paresthesias (face,
extremities), loss of reflexes and sometimes severe hypotension. Patents commonly remain
conscious although paralyzed.
Corynebacterium diphtheriae
 Morphology:
ABCDEFG:
1) Gram ⊕ rod; Coryne = club shaped.
2) Often found in clumps (classically said to resemble ADP-ribosylation
Chinese characters) or joined in V- or Y-shaped chains. β-prophage
3) Their cytoplasm contains metachromatic granules that Corynebacterium
stain with aniline dyes (eg. methylene blue).
Diphtheriae
 Virulence: (Diphtheria exotoxin)
Elongation Factor 2
1) Encoded by β-prophage.
 Non-pathogenic Corynebacterium can cause severe Granules
pseudomembranous pharyngitis after acquiring the
Tox gene via lysogenization by a temperate bacteriophage.
2) 2-subunit AB exotoxin that inhibits protein synthesis via ADP-ribosylation of
EF-2.
 EF-2 is necessary for tRNA to insert new amino acids into the growing
protein chain during translation.
 Disease:
1) Transmitted via respiratory droplets. Colonize the respiratory tract.
2) Symptoms include pseudomembranous pharyngitis (grayish-white membrane)
with lymphadenopathy (“bull neck”).
3) Myocarditis (Cardiomyopathy is the most common cause of death) and
arrhythmias.
 The B (binding) subunit binds specifically to the heparin-binding
epidermal growth factor receptor on cardiac and neural cells.
 Lab diagnosis
1) Based on gram ⊕ rods with metachromatic (blue and red) granules.
2) ⊕ Elek test for toxin.
3) Black colonies on cystine-tellurite agar.
40 Microbiology
 Treatment of an acute C. diphthariae infection: requires administration of (in order of

importance):
1) Diphtheria antitoxin (passive immunization) neutralize the toxin but is ineffective
against toxin that has already gained access to cardiac or neural cells.
2) Penicillin or erythromycin.
3) DPT vaccine.
Listeria monocytogenes
 Morphology:
1) Gram ⊕, facultative intracellular rod (significant
disease in patients with cell-mediated
immunodeficiency.)
2) Forms ―rocket tails‖ ―actin rockets‖ (red in A) via
actin polymerization that allow intracellular movement
and cell-to-cell spread across cell membranes, thereby
avoiding antibody.
3) Characteristic tumbling motility at 22° C.
4) Grows well at refrigeration temperatures (4°–10°C; ―cold enrichment‖).
 Allows the bacteria to contaminate refrigerated food (eg, meat,
unpasteurized milk, soft cheese, raw vegetables).
5) The only G +ve bacteria with endotoxin (Listeriolysin O), which allows it to
evade phagosome killing, cell-mediated immunity required to fight infection.
6) Produces a very narrow zone of beta-hemolysis on blood agar.
 Transmission:
1) Ingestion of unpasteurized dairy products and cold deli meats.
2) Transplacental transmission, or by vaginal transmission during birth.
 Pregnant women should avoid cold deli foods.
 Diseases:
1) Pregnant Women: amnionitis, septicemia, spontaneous abortion.
2) Infants: granulomatosis infantiseptica; neonatal meningitis.
3) Immunocompromised: meningitis (most common cause in adults with cancer or
renal transplant).
4) Healthy individuals: selflimited gastroenteritis.
41 Microbiology
 Treatment:
1) Ampicillin.
2) Add Gentamicin for immunocompromised.
Nocardia vs Actinomyces
 Sulfur granules: yellow aggregations of organisms bound together by proteins (Sulfur

granules do not actually contain sulfur).
 Cervicofacial actinomyces: slowly growing and firm-feeling abscess in the face or neck
region that eventually forms cutaneous sinus tracts.
UW: Pulmonary actinomycosis develops most commonly following aspiration and can be
confused with lung abscess, malignancy or tuberculosis. Microscopic findings include
filamentous, branching, gram-positive bacteria and sulfur granules.
42 Microbiology
Tropheryma whipplei
 Morphology:
1) G⊕ bacilli that may stain G⊖ or not at all.
2) Intracellular, nearly impossible to culture.
3) Stains with Giemsa and some silver stains.
 Whipple disease:
1) Symptoms:
 Malabsorption syndrome.
 Migratory polyarthritis.
 Neurological symptoms.
 May be complicated by carditis.
2) Diagnose with duodenal biopsy:
 PAS⊕ macrophages in intestinal lamina propria ―foamy macrophages‖.
 Mesenteric lymph nodes containing non-acid-fast G⊕ bacilli or PCR.
3) Treat with:
 Doxycycline + Hydroxychloroquine or
 Ceftriaxone + TMP-SMX (only SMX component active since bacteria
lack dihydrofolate reductase, the target of TMP),
(“Foamy Whipped Cream in a CAN: Cardiac, Arthralgia, Neurologic
symptoms”)
43 Microbiology
Primary and secondary tuberculosis
 PPD ⊕ if current infection or past exposure.

 PPD ⊝ if no infection and in sarcoidosis or HIV
infection (especially with low CD4+ cell count).
 Interferon-γ release assay (IGRA) has fewer
false positives from BCG vaccination.
 Caseating granulomas A with central necrosis
(upper left) and Langhans giant cells (arrow) are
characteristic of 2° tuberculosis.
44 Microbiology
Mycobacteria
 Morphology:
 All mycobacteria are acid-fast organisms (pink rod).
 In the acid-fast stain for mycobacteria, the smear is first treated with an
aniline dye (eg, carbolfuchsin).
 The dye (red color) penetrates the bacterial cell wall, where it binds with
mycolic acids.
 The slide is then treated with hydrochloric acid and alcohol. This acid
alcohol dissolves the outer cell membranes of nontuberculous bacteria, but
the presence of mycolic acids prevents decolorization of mycobacteria.
 A counterstain (eg, methylene blue) is then applied and taken up by
decolorized bacteria.
 As a result, the carbolfuchsin acid-fast stain produces red mycobacteria
(initial stain) and blue non-acid fast bacteria.
UW: Isoniazid is an antimycobacterial agent that specifically inhibits the synthesis of

mycolic acids, which are essential components of the unique mycobacterial peptidoglycan cell
wall. Without mycolic acids, the mycobacteria lose their acid-fastness and become unable to
synthesize new cell walls or multiply.
45 Microbiology
 Types:
 Mycobacterium tuberculosis (TB, often resistant to multiple drugs).
 M avium–intracellulare (causes disseminated, non-TB disease in AIDS; often
resistant to multiple drugs).
 Prophylaxis: with azithromycin when CD4+ count < 50 cells/mm3.
 M scrofulaceum (cervical lymphadenitis in children).
 M marinum (hand infection in aquarium handlers).
 TB symptoms:
 Fever, night sweats, weight loss, cough (nonproductive or productive), and
hemoptysis.
 Virulence:
 Cord factor:
 Responsible for the growth of thick, ropelike cords of mycobacterial
organisms in a twisted, "serpentine" pattern.
 Correlates with virulence; mycobacteria that do not possess cord factor
are not able to cause disease.
 Activates macrophages (promoting granuloma formation)
 Induces release of TNF-α.
 Sulfatides (surface glycolipids)  Inhibit phagolysosomal fusion.
Leprosy (Hansen disease)

 Morphology:
 Caused by Mycobacterium leprae, an acid-fast bacillus that likes cool
temperatures (infects skin and superfcial nerves—―glove and stocking‖ loss of
sensation A) and cannot be grown in vitro.
 Diagnosed via skin biopsy or tissue PCR.
 Reservoir in United States: armadillos.
 Transmission:
 Respiratory route associated with poor heigyne.
 Prolonged direct skin-to-skin contact.
 Infection has also been associated with armadillo contact in the southwestern
United States.
 Hansen disease has 2 forms (many cases fall temporarily between two extremes):
 Lepromatous:
 The most severe form. Lepromatous form can be lethal.
 Presents diffusely over the skin, with leonine (lion-like) facies B, and is
communicable.
 Characterized by low cell-mediated immunity with a humoral Th2
response.
46 Microbiology
 Macrophage signaling to kill M leprae is limited, leading to

mycobacterial dissemination.
 Tuberculoid:
 Least severe form and is often self-limited.
 Limited by an intact CMI response (Th1-mediated).
 Limited to a few hypoesthetic, hairless skin plaques.
 Treatment:
 Dapsone and rifampin for tuberculoid form.
 Clofazimine is added for lepromatous form.
47 Microbiology
Gram-negative lab algorithm
Lactose-fermenting enteric bacteria

 Fermentation of lactose  pink colonies on MacConkey agar. Lactose is key.
 Examples include Klebsiella, E coli, Enterobacter, and Serratia (weak fermenter).
 E coli produces β-galactosidase, which breaks down lactose into glucose and
galactose.
 Test with MacConKEE’S agar.
 EMB agar:
 Lactose fermenters grow as purple/ black colonies.
 E coli grows colonies with a green sheen.
48 Microbiology
Neisseria
 Morphology:
 Gram ⊝ diplococci. Metabolize glucose.
 MeninGococci ferment Maltose and Glucose.
 Gonococci ferment Glucose.
 N gonorrhoeae is often intracellular (within neutrophils).
 Culture on blood agar or VPN/Thayer-Martin agar (Vancomycin, Polymyxin,
Nystatin – Neisseria the only genus that grows on it)  selective media.
 Virulence:
 IgA proteases: allows oropharynx colonization.
 Contain lipooligosaccharides (LOS) with strong endotoxin activity.
 The outer membrane Iipooligosaccharide (LOS) of Neisseria is analogous
to the lipopolysaccharide (LPS) of enteric gram-negative rods, but it lacks
the repeating O antigen of enteric LPS.
 Responsible for many of the toxic effects (sepsis) observed in meningitis
and meningococcemia due interaction with TLR of macrophages.
 Blood levels of LOS correlate closely with morbidity and mortality.
 Pili:
 Enables nasopharyngeal initial attachment.
 High antigenic variability allows it to avoid immune response  no
vaccine available.
 Enables the bacteria to penetrate mucosal epithelium and enter circulation.
 OPA attachment proteins: Tighter attachment to the epithelium.
49 Microbiology
N Gonorrhea diseases:
1- Gonorrhoea (Men):
 High fever, urethritis, prostatitis, epididymitis, orchitis.
2- Gonorrhoea (Women):
 High fever, endocervicitis, PID, creamy, purulent discharge.
 Scarring, infertility, ectopic pregnancies.
50 Microbiology
3- Neonatal Conjunctivitis:
 Occurs within first 5 days of life (contrast Chlamydia
conjunctivitis, which takes >7 days).
 Rapidly causes blindness if untreated.
 Use Erythromycin eye drops as prophylaxis.
4- Septic Arthritis:
 Asymmetric polyarthritis in large joints of a sexually active adult.
 Joint tap shows purulent synovial fluid that doesn’t gram stain because bacteria are
intracellular.
5- Osteomyelitis:
 Less common.
6- Fitz-Hugh-Curtis Syndrome (FHC):

 Hepatic inflammation, complication of PID when it spreads to peritoneum.
(transabdominal spread of PID)
 RUQ abdominal pain.
 “Violin string” adhesions to liver.
51 Microbiology
7- Disseminated gonococcal infection (DGI)

 Triad of polyarthralgias, skin lesions, and tenosynovitis or as purulent arthritis without
skin lesions.
 DGI is one of the most common causes of septic arthritis in sexually active young
adults.
Treatment of N gonorrhea infection:

 The treatment of choice for gonorrhea is dual therapy with (ceftriaxone +
azithromycin)
 Although ceftriaxone cures nearly all cases of isolated gonorrhea the addition of
azithromycin is recommended due to potential resistance against cephalosporins
and protection against chlamydia co-infection.
 Erythromycin eye drops for neonates (also fights potential Chlamydia infection).
 Screen sexually active women <25, those with multiple sexual partners, and partners of
infected patients.
UW: Ruptured ectopic pregnancy:
 Causes abdominal pain, vaginal bleeding and hemodynamic instability.

 Pelvic inflammatory disease is most commonly caused by Neisseria
gonorrhoeae or Chlamydia trachomatis and significantly increases the risk of
ectopic pregnancy.
UW: Diagnosis of Neisseria Gonorrhea:
 Nucleic acid amplification testing (NAAT) is the diagnostic test of choice for
gonorrhea.
 NAAT uses male urine or urethral specimens or female urine, vaginal, or
endocervical specimens to detect a virus or bacterium.
 Urethral Gram stain (intracellular G-ve diplococci) and culture can also be
obtained for diagnosis.
UW: Neisseria meningitides gain access to the meninges by colonizing the pharynx first
by the following:
o Pharynx  blood  choroid plexus  meninges.

 H. influenza meningitis by the following:
o Pharynx  lymphatics  meninges.
52 Microbiology
Haemophilus influenzae
 Morphology:
 Small gram ⊝ (coccobacillary) rod.
 Culture on chocolate agar, which contains factors V (NAD+) and X (hematin) for
growth.
 Grows in the presence of S aureus and demonstrating the "satellite
phenomenon" where H influenzae grow only near the beta-hemolytic S aureus
colonies because they produce the needed X and V factors through the hemolysis
of RBCs.
 Types: either encapsulated or unencapsulated (nontypable),
1. Encapsulated strains:
a. Divided into 6 serotypes (a-f) based on the polysaccharide structure of the
capsule.
b. Type B capsular material consists of a ribosyl and ribitol phosphate
polymer called polyribitol phosphate (PRP). It is the only serotype that
contains pentose monosaccharides rather than hexose sugars as the
carbohydrate component of the capsule.
c. The PRP capsule prevents phagocytosis and intracellular killing by
neutrophils, allowing the organism to invade the vasculature, persist in the
bloodstream, and spread hematogenously to distant sites.
d. Antibodies against the type B capsule provide immunity by promoting
opsonization and
complement fixation  vaccine are available for type B.
e. Introduction of the H. influenzae type b (Hib) vaccine has led to a
dramatic decrease in the incidence of invasive disease caused by
Haemophilus influenza type b including epiglottitis, meningitis, sepsis
and other diseases commonly caused by this bacterium.
2. Unencapsulated (Nontypable strains):
a. They are part of the normal upper respiratory tract flora but can cause
mucosal inflammation  otitis media sinusitis, and bronchitis.
b. No vaccine for them.
 Virulence:
 Produces IgA protease.
 Polysaccharide capsule (PRP) of the typable forms.
53 Microbiology
 Diseases:
 Aerosol transmission. Does not cause the flu (influenza virus does).
 HaEMOPhilus causes:
 Epiglottitis (endoscopic appearance in A, can be ―cherry red‖ in children;
―thumb sign‖ on x-ray B), Meningitis, Otitis media, and Pneumonia.
 Treatment:
 Amoxicillin +/- clavulanate for mucosal infections.
 Ceftriaxone for meningitis.
 Rifampin prophylaxis for close contacts.
 Vaccine:
 Contains type b capsular polysaccharide (polyribosylribitol phosphate)
conjugated to diphtheria toxoid or other protein. Given between 2 and 18 months
of age.
 UW: Acute epiglottitis:
 Definition:
 Rapidly progressive infection of the epiglottis leading to severe inflammation and
edema of the epiglottis and larynx and potentially acute obstruction of the
airway especially during laryngoscopy.
 Causative organism:
 The most likely pathogen in children is H. influenza type B.
 Presentation:
 Small children  fever and dysphagia.
 Older children and adults  sore throat.
 Inspiratory stridor, and drooling.
 Diagnosis:
 Confirmed by the presence of an edematous epiglottis that classically appears
cherry red though
inspection of the epiglottis should not be done unless the team is prepared to
provide a surgical airway by tracheostomy.
 “Thumb sign” on lateral cervical x-ray.
54 Microbiology
Bordetella pertussis
 Gram ⊝, aerobic coccobacillus.
 Virulence:
1. Pertussis toxin (disables Gi) functions:
 Prevents phagocytosis. Causes persistence of the organism in alveolar
macrophages and ciliated epithelial cells likely explains the prolonged
disease course.
 Induce lymphocytosis  may be mistaken as viral infection.
2. Tracheal cytotoxin:
 Responsible for the cough.
3. Pertactin:
 Promotes B pertussis adherence to the upper respiratory epithelium.
 Forms the basis of the acellular pertussis vaccine.
 Three clinical stages:
1. Catarrhal
 Low-grade fevers, coryza (similar to many routine upper respiratory
infections).
2. Paroxysmal
 Paroxysms of intense cough followed by inspiratory ―whoop‖ (―whooping
cough‖).
 Lsting >2 weeks.
 Followed by posttussive vomiting.
3. Convalescent:
 Gradual recovery of chronic cough.
 Prevented by Tdap, DTaP vaccines.
55 Microbiology
Legionella pneumophila
 Identification:
 Gram ⊝ rod.
 Gram stains poorly—use silver stain.
 Grow on charcoal yeast extract medium with iron and cysteine.
 Detected by presence of antigen in urine.
 Transmission:
 Aerosol transmission from environmental water source habitat (eg, air
conditioning systems, hot water tanks). No person-to-person transmission.
 Diseases:
 Legionnaires’ disease
 Severe pneumonia (often unilateral and lobar A), fever, GI and CNS
symptoms.
 Common in smokers and in chronic lung disease.
 Think of a French legionnaire (soldier) with his silver helmet, sitting
around a campfire (charcoal) with his iron dagger—he is no sissy
(cysteine).
 Pontiac fever
 Mild flu-like syndrome.
 Treatment:
 Macrolide (azithromycin) or quinolone (levofloxacin).
56 Microbiology
Pseudomonas aeruginosa
 Morphology:
 Aerobic, motile, gram ⊝ rod.
 Non-lactose fermenting, oxidase ⊕. Aeruginosa—
aerobic.
 Virulence:
 Endotoxin (fever, shock).
 Exotoxin A (inactivates EF-2).
 Phospholipase C (degrades cell membranes).
 Pyocyanin (generates reactive oxygen species). (blue-green pigment A); has a
grape-like fruity odor.
 Mucoid polysaccharide capsule may contribute to chronic pneumonia in cystic
fibrosis patients due to bioflm formation.
 Diseases:
 Pneumonia (especially in cystic fibrosis and ventilated
patients).
 Wound infection in burn victims.
 Corneal ulcers/keratitis in contact lens wearers/ minor
eye trauma.
 Frequently found in water  hot tub folliculitis.
 Pruritic, papulopustular rash.
 Outbreaks from public or hotel swimming pools
or hot tubs.
 Ecthyma gangrenosum:
 Rapidly progressive, necrotic cutaneous lesion B
caused by Pseudomonas bacteremia.
 Typically seen in immunocompromised
(neutropenic) patients.
 Due to perivascular bacterial invasion of arteries
and veins in the dermis and subcutaneous tissue, with subsequent release
of exotoxins destructive to human tissue.
 Malignant Otitis externa.
 Seen in elderly diabetic patients.
 Ear pain and drainage.
 Granulation tissue is seen within the ear canal is an important
characteristic finding.
 Intact tympanic membrane.
 Progression of this infection can lead to:
 Osteomyelitis of the skull base.
 Cranial nerve damage.
57 Microbiology
 PSEUDOMONAS is associated with:

 Pneumonia, pyocyanin
 Sepsis
 Ecthyma gangrenosum
 UTIs (patients with indwelling catheters)
 Diabetes, drug use
 Osteomyelitis (eg, puncture wounds)
 Mucoid polysaccharide capsule Otitis externa (swimmer’s ear)
 Nosocomial infections (catheters, equipment)
 Exotoxin A
 Skin infections (hot tub folliculitis)
 Treatments include ―CAMPFIRE‖ drugs:
 Carbapenems (imipenem, meropenem)
 Aminoglycosides (amikacin, gentamycin)
 Monobactams (Aztreonam)
 Polymyxins (eg, polymyxin B, colistin)
 Fluoroquinolones (eg, ciprofloxacin, levofloxacin)
 ThIRd- and fourth-generation cephalosporins (eg, ceftazidime, cefepime)
 Extended-spectrum penicillins (eg, piperacillin, ticarcillin.
58 Microbiology
Escherichia coli
 Morphology:
 Gram ⊝ rod.
 Produces metallic green sheen on Eosin Methylene Blue (EMB) agar.
 Lactose fermenting (produces β-galactosidase, which breaks down lactose into
glucose and galactose), sorbitol fermenting (except EHEC, which usually does
not).
 Virulence factors:
 EIEC
 Microbe invades intestinal mucosa and causes necrosis and inflammation.
Invasive; dysentery.
 Clinical manifestations similar to Shigella.
 ETEC
 Produces heat-labile and heat-stable enteroToxins.
 The heat labile toxin is Cholera-like toxin (↑cAMP).
 No inflammation or invasion;
 This toxin modify electrolyte handling by enterocytes but do not cause cell
death; therefore, no erythrocytes or leukocytes are typically noted on stool
microscopy.
 Travelers’ diarrhea (watery).
 Associated with drinking the water in a developing country like Mexico.
59 Microbiology
 EPEC
 No toxin produced. Adheres to apical surface, flattens villi, prevents absorption.
 Diarrhea, usually in children (Pediatrics).
 EHEC
 No epithelial invasion, pathogenesis caused by toxin only, Shiga-like toxin
(verotoxin) inhibits protein synthesis by inhibiting 60S ribosome, produces
bloody stool (dysentery) (Hemorrhagic), but without WBCs.
 O157:H7 is most common serotype in US.
 Often transmitted via undercooked meat (Hamburgers), raw leafy vegetables.
 Shiga-like toxin causes hemolytic-uremic syndrome:
 Shiga-like toxin damages glomerular endothelial cells, platelets aggregate
(microthrombi) around damaged cells, producing hemolysis with
schistocytes  platelet consumption, and ↓ renal blood flow.
 Triad of anemia, thrombocytopenia, and acute renal failure.
 Does not ferment sorbitol (vs other E coli) due to lack of glucoronidase.
 Antibiotics contraindicated (may produce HUS).
Hemorrhagic, Hamburgers, Hemolytic-uremic syndrome.
 EAEC “Aggregative”:
 Able to adhere to intestinal cells in an aggregative, ―stacked brick‖ pattern.
 Produces persistent diarrhea in infants in less-developed countries.
60 Microbiology
Klebsiella
 Morphology:
1. Gram ⊝ rod, oxidase⊖, urease⊕, facultative anaerobe.
2. Lactose fermenting (grows pink on MacConkey agar).
3. Very mucoid colonies A caused by abundant polysaccharide capsules.
 Diseases:
1. Pneumonia:
 Associated with diabetics, alcoholics, and hospitalized patients.
 It is intestinal flora that can be aspirated causing pneumonia.
 Lobar pneumonia esp. in upper lobes.
 Produces dark red, “currant jelly” sputum (―mucoid-appearing‖, ―thick,
mucoid, blood-tinged‖, contrast ―rust-colored‖ sputum of S. pneumoniae).
 Can form abscesses, (CXR may show cavitary lesions), often confused
with TB.
2. UTI:
 Hospitalized patients (nosocomial) with Foley catheters due to fecal
contamination.
3. Sepsis: in immunocompromised.
4. Liver Abscesses:
 Most common cause of pyogenic liver abscesses (along with E. coli).
 RUQ pain, fever, malaise.
 Treatment:
1. 3rd gen Cephalosporin + Aminoglycoside or a 5 A’s of KlebsiellA:
Carbapenem. Aspiration pneumonia
2. Use fluoroquinolone as alternative. Abscess in lungs and liver
3. Often antibiotic resistant.
Alcoholics
Di-A-betics
―Curr-A-nt jelly‖ sputum.
61 Microbiology
Proteus mirabilis
 Morphology:
 G⊖ bacilli, urease⊕, urease raises urine pH producing kidney stones,
 Non-lactose fermenting, fishy odor.
 Exhibits swarming motility (highly motile) via peritrichous (uniformly
distributed on surface) flagella (motility may aid entry into bladder.)
 Diseases:
 UTI, Kidney Stones: staghorn calculi/struvite stones (ammonium-magnesium-
phosphate), Septicemia.
Campylobacter jejuni
 Morphology:
1. Gram ⊝, comma or S shaped (with polar flagella) A,
oxidase ⊕.
2. Grows at 42°C (―Campylobacter likes the hot campfre‖).
 Transmission:
1. Fecal-oral transmission through person-to-person contact.
2. Ingestion of undercooked contaminated poultry or meat,
unpasteurized milk.
3. Contact with infected domestic animals (dogs, cats, pigs).
 Diseases:
1. Gastroenteritis:
 Most common cause of GE in US, esp. in children.
 Major cause of bloody diarrhea.
 Cause inflammatory diarrhea (initially watery later bloody), accompanied by
abdominal cramping, tenesmus and leukocytes in stool. The abdominal pain may
mimic appendicitis.
2. Guillain-Barré Syndrome:
 Causes 30% of cases in US, antigenic cross-reactivity between
Campylobacter oligosaccharides and glycosphingolipids on neural tissues.
 Demyelinating disorder with ascending paralysis.
3. Reactive Arthritis (Reiter’s Syndrome):
 Seronegative spondyloarthropathy characterized by triad of urethritis,
conjunctivitis/uveitis, arthritis (―can’t see, can’t pee, can’t bend a
knee/climb a tree‖).
 Caused by autoimmune reaction to prodromal urethritis (C. trachomatis)
or GI infection (Salmonella, Shigella, Campylobacter, Yersinia), HLA-
B27⊕, young man (<40).
62 Microbiology
 Treatment:
1. Supportive treatment with fluid and electrolytes, most strains resistant to Penicillin,
Erythromycin, Fluoroquinolones.
Salmonella vs Shigella
 Both Salmonella and Shigella are gram ⊝ rods, non-lactose fermenters, oxidase ⊝.
 Can invade the GI tract via M cells of Peyer patches.
63 Microbiology
UW: Patients with sickle cell disease (SCD) have functional asplenia as a result of multiple
infarctions of the spleen, and so they are more prone to infection by encapsulated organisms
such as Salmonella.
Both Staphylococcus aureus and Salmonella are common causes of osteomyelitis in

patients with SCD, and antibiotic coverage should be directed against both types of bacteria.
Shigella:
 Morphology:
 Non-motile, non-lactose fermenting organism.
 Does not produce H2S when grown on triple sugar iron agar.
 Virulence:
 Mucosal invasion of the M cells that overlie Payer's patches is an essential
pathogenic mechanism.
 Shigella then escapes the phagosome and spreads laterally to other epithelial cells
via actin polymerization.
 The infectious dose of the shigella is very low; as few as 10 Shigella organisms can
cause disease
 Survive the acidity of the stomach and the bacteriostatic action of bile.
 Other organisms that can cause diarrhea with only a small inoculum include
 Campylobacter jejuni (around 500 cells).
 Entamoeba histolytica (as few as 1-10 organisms).
 Giardia lamblia (as few as 1-10 organisms).
64 Microbiology
Bacteroides
 Anaerobic gram-negative bacillus.
 UW: Intraabdominal infections are polymicrobial, with Bacteroides fragilis and E. coli
being the most prominent organisms isolated.
Vibrio cholera
 Morphology:
 Gram ⊝, flagellated, comma shaped, oxidase ⊕.
 Grows in alkaline media such as thiosulfate-citrate-bile salts-sucrose (TCBS)
agar.
 Killed by acid (acid labile).
 In patients with achlorhydria or PPI, very few V cholerae organisms are
needed to cause disease.
 The morphology can be confused with Campylobacter jejuni (an S-shaped,
motile, gram-negative, oxidase-positive rod), a very common cause of diarrhea
worldwide.
 Virulence:
 Cholera enterotoxin: (Permanently activates Gs, ↑cAMP  profuse rice-water
diarrhea.)
 Same mechanism as E. coli LT toxin, A and B subunits, B subunit binds
to GM1 ganglioside on intestinal epithelium via fimbriae (non-invasive),
A subunit enters cell, produces ADP ribosylation of G protein, which
activates adenylyl cyclase and increases cAMP, producing active
secretion and decreased reabsorption of Na+ and Cl- in gut lumen, H2O
follows producing secretory diarrhea, also induces mucin secretion by
goblet cells.
 Disease:
 Profuse rice-water diarrhea:
 Watery diarrhea: stool microscopy shows flecks of mucus and sloughed
epithelial cells but not leukocytes or erythrocytes.
 Endemic to developing countries.
65 Microbiology
 Transmitted via ingestion of contaminated water or uncooked food (eg, raw

shellfish).
 Prompt oral rehydration is necessary.
 Diagnosis:
 Stool samples, which shows organisms but not WBCs (contrast Campylobacter
infection, which produces WBCs in the stool).
Vibrio parahaemolyticus/vulnificus
 Morphology:
 G⊖ bacilli, facultative anaerobe, similar lab features and pathogenesis to V.
cholera.
 Transmission:
 V. parahaemolyticus is a marine bacterium, transmitted via undercooked seafood
(leading cause of diarrhea in Japan).
 Diseases:
 Gastroenteritis: self-limiting watery diarrhea with cramping and abdominal pain.
 Cellulitis: from swimming in brackish water or shucking oysters.
Yersinia enterocolitica
 Gram ⊝ rod.
 Usually transmitted from pet feces (eg, puppies), contaminated milk, or pork.
 Disease: (pseudoappendicitis)
1. Salmonella typhi and Yersinia enterocolitica can gain access to the lymphatics
and proliferate in the mesenteric lymph nodes.
2. Y enterocolitica can cause inflammation and enlargement of the lymphoid tissue
around the appendix and terminal ileum ("pseudoappendicitis"), leading to right
lower quadrant pain that can be confused with acute appendicitis.
66 Microbiology
Helicobacter pylori
 Morphology:
1) Curved, flagellated (motile), gram ⊝ rod A.
2) Triple ⊕: catalase ⊕, oxidase ⊕, and urease ⊕
 Urease produces ammonia, creating an alkaline
environment, which helps H pylori survive in
acidic mucosa.
 Can use urea breath test or fecal antigen test for
diagnosis.
 Diseases:
1. Colonizes mainly antrum of stomach.
2. Causes gastritis and peptic ulcers (especially duodenal).
3. Risk factor for peptic ulcer disease, gastric adenocarcinoma, and MALT
lymphoma.
 Diagnosis:
1. Urease breathe test:
 The patient consumes 13C labeled urea and his breath is then monitored for
the presence of 13C labeled carbon dioxide, which would indicate the
presence of the H. pylori product urease in the stomach.
 Excellent sensitivity and specificity for both the initial diagnosis of H.
pylori infection and for monitoring treatment success.
2. Fecal antigen test.
3. Confirmatory test: Culturing the organism from gastric biopsy.
 Treatment:
1) Most common initial treatment is triple therapy: Amoxicillin (metronidazole if
penicillin allergy) + Clarithromycin + Proton pump inhibitor; Antibiotics Cure
Pylori.
67 Microbiology
Fusobacterium nucleatum
 Morphology:
1) G⊖ bacilli, slender rods with pointed ends.
2) Once thought to be part of normal flora, now considered always pathogenic.
3) Reservoir is animals and humans (mucous membranes, esp. in oropharynx).
 Virulence:
1) Ability to adhere to biofilms and previously existing biological damage, esp. in
soft tissues.
 Presentations:
1) Periodontal disease.
2) Jaw abscesses: without draining sinus tracts (contrast Actinomyces israelii),
3) Lemierre’s Syndrome:
 Also known as postanginal shock including sepsis and human
necrobacillosis.
 Thrombophlebitis of internal jugular vein that typically occurs when
throat infection progresses to peritonsillar abscess, which ruptures
internally, then drains to nearby structures, ultimately infecting the jugular
vein, a clot may form, and pieces may break off and travel through the
right heart to the lungs as emboli, blocking pulmonary artery branches.
4) Topical Skin Ulcers.
 Treatment:
1) Penicillin G, Metronidazole, alternatively with Clindamycin, Cefoxitin, or
Chloramphenicol.
68 Microbiology
Spirochetes
 Spiral-shaped bacteria A with axial flaments.
 Includes Borrelia (big size), Leptospira, and Treponema.
BLT. Borrelia is Big.
 Only Borrelia can be visualized using aniline dyes
(Wright or Giemsa stain) in light microscopy due to
size.
 Treponema is visualized by dark-field microscopy or
direct fluorescent antibody (DFA) microscopy.
Leptospira interrogans
 Spirochete with hook-shaped ends found in water contaminated with animal urine.
 Leptospirosis
 flu-like symptoms, myalgias (classically of calves), jaundice, photophobia with
conjunctival suffusion (erythema without exudate).
 Prevalent among surfers and in tropics (eg, Hawaii).
 Weil disease (icterohemorrhagic leptospirosis)
 Severe form with jaundice and azotemia from liver and kidney dysfunction, fever,
hemorrhage, and anemia.
Bartonella henselae
 Causes the following diseases:
1. Cat-scratch disease:
 Characterized by low fever, painful
lymphadenopathy, and a self-limited
course.
2. Bacillary angiomatosis:
 In immunocompromised patients.
 Presents with red-purple papular skin lesions. These vascular
proliferations may also be found within the viscera.
 BA can be fatal if left untreated.
 Similar to Kaposi sarcoma.
3. Culture-negative endocarditis.
69 Microbiology
Lyme disease
 Caused by:
1. Borrelia burgdorferi, which is transmitted by the
Ixodes deer tick A (also vector for Anaplasma spp. and
protozoa Babesia).
2. Natural reservoir is the mouse (and important to tick
life cycle).
3. Common in northeastern United States. Commonly
encountered in forested regions, including backyards
and outdoor recreational areas.
A Key Lyme pie to the FACE:

Facial nerve palsy (typically bilateral)
Arthritis
Cardiac block
Erythema migrans
 Stage 1 (early localized)

1. Erythema migrans (typical ―bulls-eye‖ configuration B is pathognomonic but
not always present), flu-like symptoms.
 Stage 2 (early disseminated)
1. Secondary lesions, carditis, AV block, facial nerve (Bell) palsy, migratory
myalgias/transient arthritis.
 Stage 3 (late disseminated)
1. Encephalopathies, chronic arthritis.
 Treatment:
1. Doxycycline (1st line); amoxicillin and cefuroxime in pregnant women and
children.
70 Microbiology
Syphilis
 Caused by spirochete Treponema pallidum.
Primary syphilis
 Localized disease presenting with painless chancre A.
 If available, use dark-feld microscopy to visualize treponemes
in fluid from chancre B.
 VDRL ⊕ in ~ 80%.
Secondary syphilis
 Disseminated disease with constitutional symptoms,
maculopapular rash C (including palms and soles),
condylomata lata E (smooth, moist, painless, wart-like white
lesions on genitals), lymphadenopathy, patchy hair loss; also
confirmable with dark-field microscopy.
 Serologic testing: VDRL/RPR (nonspecific), confirm diagnosis
with specific test (eg, FTA-ABS).
 Secondary syphilis = Systemic. Latent syphilis (⊕ serology
without symptoms) may follow.
Tertiary syphilis
 Gummas F (chronic granulomas; large rubbery ulceration of the tongue and face),
aortitis (vasa vasorum destruction), neurosyphilis (tabes dorsalis, ―general paresis‖),
Argyll Robertson pupil (constricts with accommodation but is not reactive to light; also
called ―prostitute’s pupil‖ since it accommodates but does not react).
 Signs: broad-based ataxia, ⊕ Romberg, Charcot joint, stroke without hypertension.
 For neurosyphilis: test spinal fluid with VDRL, FTA-ABS, and PCR.
71 Microbiology
Congenital syphilis
 Presents with facial abnormalities such as
 rhagades (linear scars at angle of mouth, black arrow in G),
 snuffles (nasal discharge, red arrow in G,)
 saddle nose, notched (Hutchinson) teeth H, mulberry molars, and
 Short maxilla; saber shins; CN VIII deafness.
 To prevent, treat mother early in pregnancy, as placental transmission typically occurs
after first trimester.
72 Microbiology
Diagnosis of syphilis
 Dark-field microscopy of material scraped from the surface of the cutaneous syphilitic
lesion:
 The fastest and most direct method for diagnosis.
 T pallidum appears as a motile helical organism.
 Alternately, microscopy with immunofluorescence can be used.
 The diagnosis of syphilis is confirmed indirectly with serologic testing:
 Nontreponemal tests:
 (eg, Venereal Disease Research Laboratory [VDRL], rapid plasma reagin
[RPR]).
 Evaluate for the presence of antibody against cardiolipin (byproduct of
treponemal infection).
 These tests are affected by antitreponemal therapy and can be used to
follow disease progression and therapeutic response.
 Treponemal tests:
 (eg, fluorescent treponemal antibody absorption [FTA-ABS],
microhemagglutination assay for T pallidum [MHA-TP])
 Detect antibodies to specific treponemal antigens and are not affected by
antitreponemal therapy.
 They remain positive for life. Due to cost concerns:
VDRL false positives  The screening tests
 VDRL detects nonspecific antibody that reacts with
are RPR or VDRL.
beef cardiolipin.
 Quantitative, inexpensive, and widely available  The confirmatory
test for syphilis (sensitive but not specific). test is FTA-ABS.
 False-positive results on VDRL with:
 Viral infection (eg, EBV, hepatitis), Drugs,
Rheumatic fever, Lupus and leprosy.
Rapid plasma reagin test:

 In this test, the patient's serum is mixed with a solution of cardiolipin, cholesterol and
lecithin.
 Aggregation or "flocculation, of the sample demonstrates the presence of cardiolipin
antibodies in the patient's serum.
 This test is considered a nontreponemal serologic test because it does not detect
treponemal organisms or antibodies directed against treponemal organisms. Instead, it
detects antibodies to human cellular lipids released into the bloodstream after cell
destruction by T pallidum.
73 Microbiology
Jarisch-Herxheimer reaction
 Flu-like syndrome (fever, chills, headache, myalgia) after antibiotics are started; due to
killed bacteria (usually spirochetes) releasing toxins.
Gardnerella vaginalis
 A pleomorphic, gram-variable rod involved in bacterial vaginosis.
 Presents as a gray vaginal discharge with a fishy smell; nonpainful (vs vaginitis).
 Amine whiff test—mixing discharge with 10% KOH enhances fishy odor.
 Associated with sexual activity, but not sexually transmitted.
 Bacterial vaginosis is also characterized by overgrowth of certain anaerobic bacteria in
vagina.
 Clue cells (vaginal epithelial cells covered with Gardnerella) have stippled appearance
along outer margin (arrow in A). I don’t have a clue why I smell fish in the vagina
garden!
 Treatment: metronidazole or clindamycin.
74 Microbiology
Chlamydiae
 Morphology:
 Obligate intracellular (cannot make their own ATP.) Chlamys = cloak
(intracellular).
 2 forms:
 Elementary body (small, dense) is ―Enfectious‖ and Enters cell via Endocytosis;
transforms into reticulate body.
 Reticulate body Replicates in cell by fission; Reorganizes into elementary bodies.
 Diseases:
 Chlamydia trachomatis causes reactive arthritis (Reiter syndrome), follicular
conjunctivitis, nongonococcal urethritis, and PID.
 C psittaci—has an avian reservoir (parrots), causes atypical pneumonia.
 Chlamydophila pneumoniae and Chlamydophila psittaci cause atypical
pneumonia; transmitted by aerosol.
 Treatment:
 Azithromycin (favored because onetime treatment) or doxycycline (+ ceftriaxone
for possible concomitant gonorrhea).
 The chlamydial cell wall lacks classic peptidoglycan (due to reduced muramic
acid), rendering β-lactam antibiotics ineffective.
 Lab diagnosis:
 PCR, nucleic acid amplification test.
 Cytoplasmic inclusions (reticulate bodies) seen on Giemsa or fluorescent
antibody– stained smear.
75 Microbiology
 Pelvic inflammatory disease (PID) is most frequently caused by Neisseria gonorrhoaae

and Chlamydia trachomatis.
 Severe or inadequately treated PID can result in fallopian tube scarring, which in turn
can lead to infertility.
 Treatment must always include coverage of both organisms with a third-generation
cephalosporin (eg, ceftriaxone) as well as azithromycin or doxycycline.
Chlamydia trachomatis serotypes
Types A, B, and C
 Chronic infection, cause blindness due to follicular conjunctivitis in Africa.
ABC = Africa, Blindness, Chronic infection.
Types D–K
 Urethritis/PID, ectopic pregnancy, neonatal pneumonia (staccato cough) with
eosinophilia, neonatal conjunctivitis (1–2 weeks after birth). D–K = everything else.
 Neonatal disease can be acquired during passage through infected birth canal.
Types L1, L2, and L3  Lymphogranuloma venereum

 Starts as small, painless ulcers on genital mucosa  swollen, painful inguinal lymph
nodes that ulcerate and rupture (buboes). Treat with doxycycline.
76 Microbiology
Mycoplasma pneumonia
 Morphology:
 Pleomorphic. Bacterial membrane contains sterols for stability.
 Requires cholesterol to grow on artificial media.
 Clinically: atypical “walking” pneumonia
 Frequent outbreaks in military recruits and prisons.
 More common in patients < 30 years old.
 Insidious onset, headache, nonproductive cough, patchy or diffuse interstitial
infiltrate.
o X-ray looks worse than patient.
 Autoimmune hemolytic anemia can be seen (+ve Coomb’s test)
o Due to similarity between antigens in the cell membrane of M pneumoniae
and the cell membrane of erythrocytes (I-antigen).
o The antibodies causing this RBC destruction are called cold agglutinins.
 Diagnosis:
 High titer of cold agglutinins (IgM), which can agglutinate or lyse RBCs.
Mycoplasma gets cold without a coat (cell wall).
 Grown on Eaton agar. No cell wall. Not seen on Gram stain.
 Treatment:
 Macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since
Mycoplasma have no cell wall).
77 Microbiology
Zoonotic bacteria
 Zoonosis: infectious disease transmitted between animals and humans.
Tularemia
Also known as rabbit fever, is an infectious disease caused by the bacterium Francisella.
Symptoms may include fever, skin ulcer, and enlarged lymph nodes. Occasionally a form that
results in pneumonia or a throat infection may occur.
78 Microbiology
Rickettsial diseases and vector-borne illnesses

 Treatment: doxycycline (caution during pregnancy; alternative is chloramphenicol).
79 Microbiology
Mycology
Systemic mycoses
 All of the following can cause pneumonia and can disseminate.
 All are caused by dimorphic fungi: cold (20°C) = mold; heat (37°C) = yeast.
 Only exception is Coccidioides, which is a spherule (not yeast) in tissue.
 A mold is a fungus that grows in the form of multicellular filaments
called hyphae. In contrast, fungi that can adopt a single-celled growth habit are
called yeasts.
 Systemic mycoses can form granulomas (like TB); cannot be transmitted person-to-
person (unlike TB).
 Treatment:
Fluconazole or itraconazole for local infection.
 Amphotericin B for systemic infection.
Histoplasmosis
 Epidemic in Mississippi and Ohio River Valleys
 Transmitted by:
 Bird (eg, starlings) or bat droppings ―during cave
exploration or cleaning bird cages or coops‖.
 Pathological features 
 Macrophage filled with Histoplasma ―small ovoid
bodies‖ (smaller than RBC) A
Histo hides (within macrophages)
 Unique signs and symptoms:
 Palatal/tongue ulcers.
 Disseminated histoplasmosis causes
hepatosplenomegaly due to its predilection for the
mononuclear phagocyte system.
 CXR: Pulmonary infiltrates and hilar adenopathy.
 Diagnosis via urine/ serum antigen.
80 Microbiology
Blastomycosis
 Epidemic in  Eastern and Central US (states east of the
Mississippi River).
 Pathological features (dimorphic):
 (37-40 C) “Body temperature”  it assumes the yeast
form (single cells)  the image shows a typical large yeast
with a single, broad-based bud (same size as RBC) B.
Blasto buds broadly.
 (25-30 C) “Room temperature”  The mold form (branching hyphae).
 Unique signs and symptoms
 In immunocompetent:
 Lung infection or a flu-like illness (fever, chills, myalgia, headache
nonproductive cough) or pneumonia (fever, cough, pleuritic chest pain).
Characterized by granuloma formation.
 Pulmonary blastomycosis is diagnosed by finding the typical yeast forms.
 In immunocompromised:
 Cause disseminated disease:
 Systemic symptoms (fever, weight loss, night sweats).
 Lung involvement (cough, dyspnea).
 Skin lesions (papules, pustules, ulcers, verrucous lesions can
simulate SCC, granulomatous nodules).
 Bone pain (lytic lesions).
Coccidioidomycosis
 Epidemic in:
 endemic to the southwestern United States (desert areas) 
(Arizona, New Mexico, western Texas, southern and central
California).
 Pathological features:
 Spherule (much larger than RBC) filled with endospores of
Coccidioides.
 Unique signs and symptoms:
 Transmitted by spore inhalation  acute pneumonia (most
common) or flu like symptoms.
 Disseminates to skin/ bone.
 Erythema nodosum (desert bumps) or multiforme.
 Arthralgias (desert rheumatism).
 Can cause meningitis.
81 Microbiology
Paracoccidioidomycosis
 Epidemic in  Latin America.
 Pathological features  Budding yeast of Paracoccidioides with
―captain’s wheel‖ formation (much larger than RBC) D.
 Similar to Coccidioidomycosis, males > females.
 Paracoccidio parasails with the captain’s wheel all the way to Latin
America.
82 Microbiology
Cutaneous mycoses
Tinea (dermatophytes)
 Tinea is the clinical name given to dermatophyte (cutaneous
fungal) infections.
 Dermatophytes include Microsporum, Trichophyton, and
Epidermophyton.
 Branching septate hyphae visible on KOH preparation with
blue fungal stain A.
 Associated with pruritus.
Tinea capitis
 Occurs on head, scalp.
 Associated with lymphadenopathy, alopecia, scaling B.
Tinea corporis
 Occurs on torso.
 Characterized by erythematous scaling rings (―ringworm‖) and
central clearing C.
 Can be acquired from contact with an infected cat or dog.
Tinea cruris
 Occurs in inguinal area D.
 Often does not show the central clearing seen in tinea corporis.
Tinea pedis
 Three varieties:
 Interdigital E; most common.
 Moccasin distribution.
 Vesicular type.
83 Microbiology
Tinea unguium
 Onychomycosis; occurs on nails.
Tinea (pityriasis) versicolor

 Caused by Malassezia spp. (Pityrosporum spp.), a yeast-like fungus (not a dermatophyte
despite being called tinea).
 Degradation of lipids produces acids that damage melanocytes and cause hypopigmented
G, hyperpigmented, and/or pink patches.
 Less pruritic than dermatophytes.
 Can occur any time of year, but more common in summer (hot, humid weather).
 “Spaghetti and meatballs” appearance on microscopy H.
 Treatment: selenium sulfide, topical and/or oral antifungal medications.
84 Microbiology
Opportunistic fungal infections

Candida albicans
 Morphology: alba = white. Dimorphic; Forms:
 Pseudohyphae with blastoconida and budding yeasts at 20°C A
 Germ tubes “true hyphae” at 37°C B (in blood cultures as it has the same
temperature). Germ tube test is diagnostic of Candida albicans, and allows it to be
distinguished from other members of the Candida family.
 Candida contributes to the normal flora of skin, mouth, vagina, and intestine.
 Diseases: Systemic or superficial fungal infection.

 Oral C and esophageal thrush in immunocompromised (neonates, steroids,
diabetes, AIDS).
 Vulvovaginitis (diabetes, use of antibiotics).
 Diaper rash.
 Right sided endocarditis (IV drug users).
 Disseminated candidiasis (especially in neutropenic patients).
 Candidemia in patients receiving TPN by central venous catheter;
Candida can colonize the catheter, and the lipid emulsion in the parenteral
nutrition solution is thought to promote the growth of Candida.
 Chronic mucocutaneous candidiasis (T-cell defect).
85 Microbiology
 Treatment:
 Oral fluconazole/topical azole for vaginal.
 Nystatin, fluconazole, or caspofungin for oral/ esophageal.
 Fuconazole, caspofungin, or amphotericin B for systemic.
 Diagnosis:
 Microscopic examination of KOH-treated scrapings shows Candida yeast and
pseudohyphae.
Aspergillus fumigatus
 Morphology:
 Septate hyphae that branch at 45° Acute Angle D.
 Produces conidia in radiating chains at end of conidiophore E.
 Diseases:
1. Invasive aspergillosis:
 In immunocompromised (neutropenic), patients with chronic
granulomatous disease.
 Lung granulomas with development of fever, pleuritic chest pain and
hemoptysis.
 Aspergillus has a predilection for blood vessels and can spread
hematogenously; causing infection and infarcts involving the skin,
paranasal sinuses, kidneys, endocardium, and brain.
 Treat with Amphotericin B.
2. Aspergillomas (fungus balls):
 In pre-existing lung cavities, especially after TB infection.
86 Microbiology
3. Allergic bronchopulmonary aspergillosis (ABPA):

 Hypersensitivity response associated with asthma and cystic fibrosis.
 There is intense airway inflammation and mucus plugging with
exacerbations and remissions.
 Wheezing and migratory pulmonary infiltrates.
 Eosinophilia.
 Increased serum IgE and increased titers of IgG antibodies against
Aspergillus.
 Repeated exacerbations may produce transient pulmonary infiltrates and
proximal bronchiectasis.
 Treatment is with corticosteroids.
 Some species of Aspergillus produce Aflatoxins (associated with hepatocellular
carcinoma).
Mucor and Rhizopus spp.

 Morphology:
 Irregular, broad, nonseptate hyphae branching at
wide angles often 90 H.
 Mucormycosis:
 The infection (acquired by spore inhalation) ascends
from the nasal passage to the sinuses/orbits and then
sometimes to the brain. Fungi proliferate in blood
vessel walls, penetrate cribriform plate, and enter
brain.
 Causes disease mostly in ketoacidotic diabetic
and/or neutropenic patients (eg, leukemia).
 Tends to affect the paranasal sinuses 
 Facial and periorbital pain, headache and
purulent nasal discharge.
 The fungi proliferate in the walls of blood vessels
and cause necrosis of the corresponding tissue 
 Black necrotic eschar on face; may have cranial nerve involvement.
 Rhinocerebral, frontal lobe abscess; cavernous sinus thrombosis.
 Diagnosed by:
 Mucosal biopsy (histological examination): broad ribbon-like nonseptate hyphae
with right-angle branching.
 Differential diagnosis:
 Invasive aspergillosis causing rhinosinusitis (commonly seen in neutropenic
patients). On light microscopy, Aspergillus is seen as septate narrow hyphae
with sharp-angle branching.
87 Microbiology
 Treatment:
 Surgical debridement, amphotericin B, isavuconazole.
Cryptococcus neoformans
 Morphology:
 Not dimorphic  yeast form only (single cell); round or
oval encapsulated cells with narrow-based buds.
 Virulence factors:
 Heavily encapsulated yeast (↓ phagocytosis).
 Highlighted with India ink (clear halo F) and
mucicarmine (red inner capsule G).
 Latex agglutination test detects polysaccharide
capsular antigen and is more specific.
 Culture on Sabouraud agar.
 Transmission:
 Found in soil, pigeon droppings.
 Acquired through inhalation with hematogenous
dissemination to meninges.
 Lungs are the primary site of infection but is
usually asymptomatic.
 Cleared by macrophages and T cells.
 Diseases: typically affects only immunocompromised patients (opportunistic pathogen)
 Although lung infection occurs first, it is usually
asymptomatic. Cryptococcal pneumonia is
diagnosed by mucicarmine staining of lung tissue
and bronchoalveolar washings.
88 Microbiology
 Meningoencephalitis is the most common presentation (―soap bubble‖ lesions in

brain).
Pneumocystis jirovecii
 Yeast-like fungus (originally classified as protozoan).
 Inhaled. Most infections are asymptomatic.
 Clinical picture:
 Immunosuppression (eg, AIDS) predisposes to disease.
 Causes Pneumocystis pneumonia (PCP), a diffuse interstitial pneumonia A.
 Diffuse, bilateral ground-glass opacities on CXR/CT B.
 Diagnosed by:
 Lung biopsy or lavage.
 Disc-shaped yeast seen on methenamine silver stain of lung tissue C.
 Treatment/prophylaxis:
 TMP-SMX.
 In sulfa allergy  pentamidine, dapsone (prophylaxis only), atovaquone.
 Start prophylaxis when CD4+ count drops to < 200 cells/mm3 in HIV patients.
89 Microbiology
Sporothrix schenckii
 Morphology:
 Dimorphic, cigar-shaped budding yeast that
grows in branching hyphae with rosettes of
conidia; lives on vegetation.
 Diseases: (Sporotrichosis)
 When spores are traumatically introduced into
the skin, typically by a thorn (―rose
gardener’s disease‖).
 Causes local pustule or ulcer A with nodules along draining lymphatics (ascending
lymphangitis).
 Disseminated disease possible in immunocompromised host.
 Treatment:
 Itraconazole or potassium iodide.
Think of a rose gardener who smokes a cigar and pot.
90 Microbiology
Parasitology
Protozoa—gastrointestinal infections
 UW: Giardia lamblia cysts: ellipsoidal cysts with smooth, well-defined walls and
2+ nuclei.
91 Microbiology
Protozoa—CNS infections
UW: HIV who has seizures and multiple ring-enhancing lesions with mass effect 
cerebral toxoplasmosis.
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Protozoa—hematologic infections
93 Microbiology
Malaria:
UW: P vivax and P ovale:
 Unique in that they also establish a latent

hepatic infection (exo-erythrocytic cycle) in
the form of hypnozoites; responsible for
relapses.
 Resistant to chloroquine; add primaquine to
eradicate these hypnozoites.
94 Microbiology
Babesia:
 Fever + hemolytic anemia + thrombocytopenia + ↑LFTs + cross-shaped
intraerythrocytic inclusions “maltese cross”.
 Splenectomy  severe babesiosis, which can manifest as acute respiratory distress
syndrome.
 Ixodes tick transmits 3 diseases: Lyme, Babesiosis, Human Granulocytic

anaplasmosis.
 Aedes mosquito: vector tor dengue fever and chikungunya.
95 Microbiology
Protozoa—others
UW: Trypanosoma Cruzi
 Produces a neurotoxin that destroys the myenteric plexi  causes intramural,

parasympathetic denervation of smooth muscle in the esophagus, intestines, and
ureters, causing secondary achalasia megacolon, and megaureter, respectively.
 In the esophagus this neurotoxin incapacitates the lower esophageal sphincter, so
that food gets "stuck” in the esophagus. Proximal to this obstruction, the
esophagus is markedly dilated.
 Dysphagia for liquids and difficulty belching in association with a dilated
esophagus and absent peristalsis in the smooth muscle portion of the esophagus is
diagnostic of achalasia.
96 Microbiology
Nematode routes of infection

 Ingested—Enterobius, Ascaris, Toxocara, Trichinella
o You’ll get sick if you EATT these!
 Cutaneous—Strongyloides, Ancylostoma, Necator
o These get into your feet from the SANd.
 Bites—Loa loa, Onchocerca volvulus, Wuchereria bancrofti
o Lay LOW to avoid getting bitten.
Nematodes (roundworms)
97 Microbiology
Entrobious vermicularis (pinworm)

 Enterobiasis is the most common helminthic infection in the United States, occurring
most frequently in children age 5-10.
 In contrast to other worms that release their eggs into the intestine, the female worm
migrates out through the rectum onto the perianal skin to deposit eggs (most commonly at
night).
 Diagnosis is made by the Scotch tape test (ie, microscopy of adhesive tape applied to
perianal region), which reveals the presence of oval, asymmetrically flattened eggs with a
bean-shaped appearance.
 Treatment:
1. Albendazole is the first-line treatment.
2. Pyrantel pamoate is an alternate agent preferred in pregnant patients.
98 Microbiology
Strongyloides stercoralis
 The infection is transmitted by filariform (infectious) larvae found in soil contaminated
with human feces.
 On contact, the larvae penetrate the skin and migrate hematogenously to the
lungs.
 There they enter the alveoli and travel up the bronchial tree to the pharynx, where
they are swallowed.
 When the larvae reach the intestine, they develop into adults that lay eggs within
the intestinal mucosa.
 These hatch into rhabditiform (noninfectious) larvae that migrate into the
intestinal lumen to be excreted in the stool.
 Strongyloides hyperinfection:
 Some rhabditiform larvae can molt directly into filariform larva within the
intestine and re-infect the host by penetrating the intestinal wall or perianal skin.
99 Microbiology
 This cycle of autoinfection can result in a massive increase in worm burden,

leading to widespread dissemination of the parasites throughout the body
(hyperinfection).
 The ensuing inflammation can be severe enough to cause multiorgan
dysfunction and septic shock.
 Hyperinfection occurs most often in patients taking immunosuppressants (eg,
corticosteroids) or with HTLV-1 infection. These patients have impaired Th2-
directed cellular immunity (mediated by the antihelmintic action of eosinophils
and basophils).
 The diagnosis is made by:
 Finding rhabditiform (non-infectious) larvae in the stool, as the eggs and adult
parasites are usually seen only in intestinal biopsies.
 Treatment is with ivermectin.
100 Microbiology
Cestodes (tapeworms)
UW: seizures in patients from Central and South America + brain cysts 
neurocystocyrcosis.
101 Microbiology
Trematodes (flukes)
Shistosomiasis:
 The clinical manifestations of schistosomiasis result from a Th2-mediated
granulomatous response directed against the eggs that is composed of infiltrating Th2
cells, eosinophils, and M2 macrophages.
 This ultimately leads to the development of marked fibrosis and ulceration and scarring
of the bowel or bladder/ureters (depending on the species).
 Eggs that settle into the presinusoidal radicals of the portal vein can cause periportal
"pipestem" fibrosis (pathognomonic for hepatic schistosomiasis).
102 Microbiology
Ectoparasites
103 Microbiology
UW: The rash of scabies is often worse at night and is due to a delayed type IV
hypersensitivity reaction to the mite, mite feces, and mite eggs.
UW: Skin examination in scabies:
1. Excoriations with small, crusted, red papules scattered around the region.
2. Patients can also develop small vesicles, pustules, or wheals.
3. Linear burrows are the most specific finding in scabies, although they are often
obscured by excoriations.
4. Diagnosis is confirmed by:
 Skin scrapings from excoriated lesions that show mites, ova, and feces
under light microscopy.
104 Microbiology
Virology
Viral structure— general features
 Viral tropism for specific tissues and invasion of cells is determined by viral envelope
or capsid surface proteins.
 UW: Ether and other organic solvents dissolve the lipid bilayer that makes up the outer
viral envelope. Loss of infectivity after ether exposure is a characteristic feature of
enveloped viruses.
 Changes in host range are most commonly caused by a mutation in the viral encoded
envelope surface glycoprotein that mediates virion attachment to target host cell
plasmalemma receptors.
 One such example would be a mutation in the hemagglutinin of an influenza A
strain that was previously confined to domestic livestock. If the mutation
conferred a new binding affinity for a neuraminic acid-containing glycoprotein on
the surface of human nasopharyngeal epithelial cells, then the virus would no
longer be a threat only to domestic livestock and humans would be vulnerable to
infection.
105 Microbiology
Viral genetics
Recombination
 Exchange of genes between 2 chromosomes by crossing over within regions of
significant base sequence homology.
Reassortment
 When viruses with segmented genomes (eg, influenza virus) exchange genetic material.
 For example, the 2009 novel H1N1 influenza A pandemic emerged via complex viral
reassortment of
genes from human, swine, and avian viruses. Has potential to cause antigenic shift.
Complementation
 When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional
protein, the nonmutated virus ―complements‖ the mutated one by making a functional
protein that serves both viruses.
 For example, hepatitis D virus requires the presence of replicating hepatitis B virus to
supply HBsAg, the envelope protein for HDV.
106 Microbiology
Phenotypic mixing
 Occurs with simultaneous infection of a cell with 2 viruses.
 Genome of virus A can be partially or completely coated (forming pseudovirion) with the
surface proteins of virus B.
 Type B protein coat determines the tropism (infectivity) of the hybrid virus.
 However, the progeny from this infection have a type A coat that is encoded by its type A
genetic material.
Viral vaccines
Live attenuated vaccines

 MMR, Yellow fever, Rotavirus, Influenza (intranasal), Chickenpox (VZV), Smallpox,
Sabin polio virus.
―Music and LYRICSS are best enjoyed Live.‖
 MMR = measles, mumps, rubella; live attenuated vaccine that can be given to HIV ⊕
patients who do not show signs of immunodeficiency.
Killed
 Rabies, Influenza (injected), Salk Polio, and HAV vaccines.
 Killed/inactivated vaccines induce only humoral immunity but are stable.
SalK = Killed.
RIP Always.
107 Microbiology
Subunit
 HBV (antigen = HBsAg).
 HPV (types 6, 11, 16, and 18).
DNA viral genomes

 All DNA viruses are dsDNA except the Parvoviridae.
 All are dsDNA (like our cells), except ―part-of-avirus‖ (parvovirus) is ssDNA. Parvus
= small.
 All are linear except papilloma-, polyoma-, and hepadnaviruses (circular).
RNA viral genomes

 All RNA viruses are ssRNA except Reoviridae.
 All are ssRNA (like our mRNA), except ―repeato-virus‖ (reovirus) is dsRNA.
 ⊕ stranded RNA viruses: I went to a retro (retrovirus) toga (togavirus) party, where I
drank flavored (flavivirus) Corona (coronavirus) and ate hippie (hepevirus) California
(calicivirus) pickles (picornavirus).
Naked viral genome infectivity

 Purified nucleic acids of most dsDNA (except poxviruses and HBV) and ⊕ strand
ssRNA (≈ mRNA) viruses are infectious.
 Naked nucleic acids of ⊝ strand ssRNA and dsRNA viruses are not infectious. They
require polymerases contained in the complete virion.
Viral replication
DNA viruses  All replicate in the nucleus (except poxvirus). “Pox is out of the box
(nucleus).”
RNA viruses  All replicate in the cytoplasm (except influenza virus and retroviruses).
108 Microbiology
Viral envelopes
 Naked (nonenveloped) viruses include Papillomavirus, Adenovirus, Parvovirus,
Polyomavirus, Calicivirus, Picornavirus, Reovirus, and Hepevirus.
 Give PAPP smears and CPR to a naked hippie (hepevirus).
DNA = PAPP; RNA = CPR and hepevirus
 Generally, enveloped viruses acquire their envelopes from plasma membrane when they
exit from cell.
 Exceptions include herpesviruses, which acquire envelopes from nuclear
membrane.
DNA virus characteristics
109 Microbiology
DNA viruses
110 Microbiology
Herpesviruses
 Enveloped, DS, and linear viruses.
111 Microbiology
Herpetic gingivostomatitis
 The most common clinical manifestation of primary herpes simplex (HSV-1) infection.
 It occurs most often in children aged 1-3 years.
 Results in fever, vesiculoulcerative lesions of the oral mucous membranes, and localized
lymphadenopathy.
 Herpetic gingivostomatitis is considered a primary infection.
 HSV-1 that persistently resides in the trigeminal ganglia is the predominant
pathogen responsible for recurrent oral-labial herpes  herpetic fever blisters
or "cold sores" tend to favor the facial skin around mucosal orifice.
HSV-1 primary infection  gingivostomatitis.
HSV-1 reactivation  perioral blisters or "cold sores”
Herpes zoster:
 Unilateral vesicular rash localized on a single
dermatome in an elderly patient.
 Arises when latent varicella zoster virus (VZV)
infection is reactivated within a single dorsal root
sensory ganglion.
 Localized dermatomal pain that persists for several
months following a zoster eruption is termed
postherpetic neuralgia (PHN) and is the most common
neurologic complication of VZV infection.
112 Microbiology
HSV encephalitis
 Diagnosis:
1. Imaging: edema and hemorrhagic necrosis of the temporal lobe.
2. Definitive diagnosis is made by PCR testing of cerebrospinal fluid.
Genital herpes:
 Recurrent genital HSV generally due to reactivation of latent HSV-2 infection within
the S2, S3, and S4 dorsal root (sensory) ganglia.
 Recurrence of genital HSV can be suppressed or minimized with daily oral valacyclovir
(preferred as it is dosed once daily and has good bioavailability), acyclovir, or
famciclovir.
 Although the antiviral agents may not be active against latent virus forms, they can
suppress further multiplication as soon as reactivation occurs.
 A short (7-10 days) course of treatment with oral acyclovir during primary genital HSV
infection usually reduces the duration of viral shedding, time for lesional healing, and
local pain: however, it does not appear to alter recurrence rates.
113 Microbiology
Roseola infantum:
 HHV-6 is one of the most common causes of febrile seizures.
 Differential diagnosis:
 Rubella and measles:
 Maculopapular rash on the face that then spreads to the trunk and
extremities.
 Roseola infantum:
 The rash usually starts on the trunk and spreads to the face and
extremities.
 Erythema infectiosum, or fifth disease (Parvo virus B19):
 Slapped cheek rash and truncal reticular rash.
Epstein-Barr virus (EBV)

 Infects B cells, stimulating them to proliferate continuously ("transformation" or
"immortalization").
 EBV is an oncogenic virus that promotes polyclonal B cell proliferation and heterophile
antibody production.
 The immortalized B cells maintain the ability to secrete immunoglobulins (Ig) and B-
cell activation products (eg CD23) with very few of them releasing virus particles at any
one time.
 EBV typically causes a latent infection of B cells, with viral genome persistence but no
full virion replication, no lytic release, and sparse viral protein expression.
 Normally, only minimal amounts of EBV-specific antigens circulate in an
immunocompetent host; therefore, blood tests for viral antigens are insensitive to latent
EBV infection. Detection of circulating surface antigen is used to diagnose hepatitis B
virus infection.
114 Microbiology
Cytomegalovirus (CMV)
 Congenital CMV  chorioretinitis (most common eye-related problem), sensorineural
deafness, seizures, jaundice, hepatomegaly splenomegaly, and microcephaly.
 Causes pneumonia in a transplant patient.
HSV identification
 Viral culture for skin/genitalia.
 PCR in case of:
 CSF PCR for herpes encephalitis.
 PCR of skin lesions is currently test of choice.
 Tzanck test:
 A smear of an opened skin vesicle to detect multinucleated giant cells A
commonly seen in HSV-1, HSV-2, and VZV infection.
 Intranuclear eosinophilic Cowdry A inclusions also seen with HSV-1, HSV-2,
VZV.
Tzanck heavens I do not have herpes.
 Direct fluorescence antibody.
115 Microbiology
Parvovirus B19
 The blood group P antigen, globoside, is a parvovirus B19 receptor that is expressed in
high concentrations on mature erythrocytes and erythroid progenitors.
 As a result, parvovirus B19 is highly tropic for erythrocyte precursors,
particularly pronormoblasts and normoblasts, and replicates predominantly in the
bone marrow.
 Erythema infectiosum (fifth disease) ―slapped cheecks‖

 The prodrome of low-grade fever, headache, malaise and upper respiratory
symptoms.
 2-5 days later  sudden appearance of an erythematous malar rash (bright-red
cheeks that feel burning hot) with circumoral pallor (spares the nasolabial folds).
 The facial rash fades, an erythematous rash in a reticular, lacelike pattern often
appears on the trunk and extremities.
 Cause of the rash of erythema infectiosum:
 Local immune complex deposition once serum levels of virus-specific
IgM and IgG have attained high enough levels.
116 Microbiology
Human papilloma virus
 HIV infection increases the prevalence of HPV infection and the risk of anal carcinoma;
this risk is further augmented in men who have sex with men.
Adenovirus
 Adenovirus is the most common known viral cause of acute hemorrhagic cystitis
outbreaks in children.
 Also causes pharyngoconjunctival fever:
 Febrile pharyngitis, cough, nasal congestion, conjunctivitis, and enlarged cervical
nodes.
 Outbreaks in small groups of individuals who are living in crowded quarters (eg,
barracks) under conditions of fatigue or stress (military recruits or campers)
Receptors used by viruses
117 Microbiology
RNA viruses
118 Microbiology
Negative-stranded viruses
 Must transcribe ⊝ strand to ⊕.
 Virion brings its own RNA-dependent RNA polymerase.
 They include Arenaviruses, Bunyaviruses, Paramyxoviruses, Orthomyxoviruses,
Filoviruses, and Rhabdoviruses. Always Bring Polymerase Or Fail Replication.
Segmented viruses
 All are RNA viruses.
 They include Bunyaviruses, Orthomyxoviruses (influenza viruses), Arenaviruses, and
Reoviruses. BOAR.
Picornavirus
 Includes Poliovirus, Echovirus, Rhinovirus, Coxsackievirus, and HAV.
PicoRNAvirus = small RNA virus. PERCH on a ―peak‖ (pico).
 RNA is translated into 1 large polypeptide that is cleaved by proteases into functional
viral proteins.
 Can cause aseptic (viral) meningitis (except rhinovirus and HAV).
 All are enteroviruses except rhinovirus.
Rhinovirus (Rhino has a runny nose)

 A picornavirus. Nonenveloped RNA virus.
 Cause of common cold; > 100 serologic types.
 Acid labile—destroyed by stomach acid; therefore, does not infect the GI tract (unlike
the other picornaviruses).
Yellow fever virus

 A flavivirus (also an arbovirus) transmitted by Aedes mosquitoes.
 Virus has a monkey or human reservoir.
 Symptoms:
 High fever, black vomitus, and jaundice. Flavi = yellow, jaundice.
 May see Councilman bodies (eosinophilic apoptotic globules) on liver biopsy.
119 Microbiology
Rotavirus
 Rotavirus A, the most important global cause of infantile
gastroenteritis.
 Segmented dsRNA virus (a reovirus).
 Major cause of acute diarrhea in the United States during winter,
especially in day care centers, kindergartens. Villous destruction
with atrophy leads to ↓ absorption of Na+ and loss of K+.
ROTAvirus = Right Out The Anus.
 CDC recommends routine vaccination of all infants except those
with a history of intussusception or SCID.
Influenza viruses
 Morphology:
 Orthomyxoviruses. Enveloped, ⊝ ssRNA viruses with 8-segment genome.
 Contain:
 Hemagglutinin (binds sialic acid and promotes viral entry).
 Neuraminidase (promotes progeny virion release) antigens.
 Patients at risk for fatal bacterial superinfection, most commonly S aureus, S
pneumoniae, and H influenzae.
Genetic shift/ antigenic shift

 Causes pandemics.
 Reassortment of viral genome segments, such as when
segments of human flu A virus reassort with swine flu A
virus.
Sudden shift is more deadly than gradual drift.
 Viruses with segmented genomes (eg, orthomyxoviruses
and rotaviruses) are capable of genetic shifts through
reassortment.
Genetic drift/ antigenic drift

 Causes epidemics.
 Minor (antigenic drift) changes based on random mutation
in hemagglutinin or neuraminidase genes.
120 Microbiology
Rubella virus
 A togavirus. Causes rubella, once known as German (3-day)
measles.
 Presentations:
 Generalized lymphadenopathy, particularly postauricular
and occipital.
 Fever, arthralgias.
 Maculopapular rash:
 Fine, confluent rash.
 Starts on face and spreads centrifugally to involve trunk and extremities
A.
 Causes mild disease in children but serious congenital disease (a ToRCHeS
infection) 
Congenital rubella: findings include:
 ―Blueberry muffin‖ appearance due to dermal extramedullary
hematopoiesis.
 Head (microcephaly, mental retardation), eyes (cataracts) ears (deafness),
and heart/cardiovascular system (patent ductus arteriosus, peripheral
pulmonic stenosis).
 The most classic clinical triad of congenital rubella includes
1. Congenital cataracts (white pupils).
2. Sensory-neural deafness.
3. Patent ductus arteriosus.
 To decrease the incidence of this syndrome the CDC currently
recommends the vaccination of children and non-pregnant females of
childbearing age with live, attenuated rubella virus vaccine.
UW: Measles (rubeola) and German measles (rubella) are characterized by a maculopapular
rash that
begins on the face and spreads to the trunk and extremities.
 Rubella typically spreads faster and does not darken or coalesce.

 Postauricular and occipital lymphadenopathy is particularly common in rubella.
121 Microbiology
Paramyxoviruses
 Paramyxoviruses cause disease in children.
 They include those that cause parainfluenza (croup: seal-like, brassy, barking cough),
mumps, measles, RSV, and human metapneumovirus, which causes respiratory tract
infection (bronchiolitis, pneumonia) in infants.
 All contain surface F (fusion) protein, causes respiratory epithelial cells to fuse and
form multinucleated cells.
 Palivizumab (monoclonal antibody against F protein) prevents pneumonia caused
by RSV infection in premature infants. Palivizumab for Paramyxovirus (RSV)
Prophylaxis in Premies.
Croup (acute laryngotracheobronchitis)

 Caused by parainfluenza viruses (paramyxovirus).
 Virus membrane contains hemagglutinin (binds sialic acid and
promotes viral entry) and neuraminidase (promotes progeny
virion release) antigens.
 Results in a “seal-like” barking cough and inspiratory stridor.
 Narrowing of upper trachea and subglottis leads to characteristic
steeple sign on x-ray A.
 Severe croup can result in pulsus paradoxus 2° to upper airway obstruction.
122 Microbiology
Mumps virus
 A paramyxovirus that causes mumps, uncommon due to effectiveness of MMR vaccine.

 Symptoms: Parotitis A, Orchitis (inflammation of testes), aseptic Meningitis, and
Pancreatitis.
 Can cause sterility (especially after puberty).
 Mumps makes your parotid glands and testes as big as POM-Poms.
123 Microbiology
Measles (rubeola) virus

 A paramyxovirus that causes measles.
 Usual presentation involves:
 Prodromal fever with cough, coryza, and conjunctivitis.
3 C’s of measles: Cough, Coryza, Conjunctivitis.
 Then eventually Koplik spots (bright red spots with blue-
white center on buccal mucosa A).
 Followed 1–2 days later by a maculopapular rash B
1. Cephalocaudal: starts at the head/neck and spreads
downward.
2. Centrifugal spread.
3. Usually spares palms/soles
 Complications:
 Primary measles pneumonia (Giant cell pneumonia)
(rarely, in immunosuppressed)
 Secondary bacterial infections (pneumonia & otitis media).
 Neurologic:
1. Encephalitis (within days)
2. Acute disseminated encephalomyelitis (within weeks)
3. Subacute sclerosing panencephalitis SSPE (within years)
 Lymphadenitis with WarthinFinkeldey giant cells (fused lymphocytes) in a
background of paracortical hyperplasia.
 Vitamin A supplementation can reduce morbidity and mortality from measles,
particularly in malnourished children.
124 Microbiology
Rabies virus
 Morphology:
 Bullet-shaped virus A.
 Negri bodies (cytoplasmic inclusions B) commonly found
in Purkinje cells of cerebellum and in hippocampal neurons.
 Pathogenesis:
 Infection more commonly from bat, raccoon, and skunk
bites than from dog bites in the United States; aerosol
transmission (eg, bat caves) also possible.
 Rabies has long incubation period (weeks to months) before
symptom onset.
 Travels to the CNS by migrating in a retrograde fashion
(via dynein motors) up nerve axons after binding to ACh
receptors.
 Disease:
 Progression of disease: fever, malaise  agitation, photophobia, hydrophobia,
hypersalivation, painful spasms (pharyngospasm)  paralysis, coma  death.
 Prevention & treatment:
 Postexposure prophylaxis is wound cleaning plus immunization with killed
vaccine and rabies immunoglobulin. (Example of passive-active immunity.)
 Once the symptoms of rabies encephalitis appear, post-exposure prophylaxis is no
longer effective.
125 Microbiology
Ebola virus
 A filovirus A that targets endothelial cells, phagocytes, hepatocytes.
 Transmission:
 Transmission requires direct contact with bodily fluids, fomites
(including dead bodies), infected bats or primates (apes/monkeys);
high incidence of nosocomial infection.
 Presentation:
 Following an incubation period of up to 21 days, presents with
abrupt onset of flu-like symptoms, diarrhea/vomiting, high fever,
myalgia.
 Can progress to DIC, diffuse hemorrhage, shock. High mortality rate.
 Diagnosed with RT-PCR within 48 hr of symptom onset.
 Supportive care, no definitive treatment. Strict isolation of infected individuals and
barrier practices for health care workers are key to preventing transmission.
Zika virus
 A flavivirus most commonly transmitted by Aedes mosquito bites.
 Diseases:
 In adults: causes conjunctivitis, low-grade pyrexia, and itchy rash in 20% cases.
 Outbreaks more common in tropical and subtropical climates.
 In embryo: can lead to congenital microcephaly or miscarriages if transmitted in
utero.
 Sexual and vertical transmission possible.
 Diagnose with RT-PCR or serology.
 Supportive care, no definitive treatment.
126 Microbiology
Dengue Viruses
 Morphology:
 Single-stranded RNA viruses (genus Flavivirus) with 4 different serotypes
(DENV1-4).
 Transmission:
 By the Aedes mosquito. (Also transmits Zika, Yellow fever, Chikungunya).
 Disease:
 Primary (first) infection can be asymptomatic or cause a self-limited disease in
most adults.
 Primary infection leads to lifelong immunity against the same serotype,
but individuals can be infected with a different serotype.
 Secondary infection with a different viral serotype can cause a more severe
illness, possibly due to antibody-dependent enhancement of infection, enhanced
immune complex formation, and/or accelerated (not blunted) T-lymphocyte
responses.
UW: Chikungunya:
 A febrile illness with flulike symptoms, prominent polyarthralgia/arthritis (hands,

wrists, ankles), and diffuse macular rash.
 Transmitted with Aedes as Dengue fever; as a result many areas have had
simultaneous outbreaks of both dengue and chikungunya.
 Preventive measures against both infections include protective barriers (eg, bed
nets, window screens) and insect spraying.
127 Microbiology
West Nile Virus

 Morphology:
 Single-strand RNA flavivirus.
 Transmission:
 By female mosquitos (Culex), most commonly in the summer.
 Symptoms:
 Fever, rash.
 CNS: encephalitis (confusional state) or meningitis associated with a flaccid
paralysis syndrome.
 Diagnosis:
 Positive CSF anti-WNV antibodies (PCR testing often not needed).
UW: Other arboviruses (ARthropod-BOurne viruses) transmitted by insect bites,

including the Togaviridae (Eastern, Western and Venezuelan equine encephalitis) and the
Bunyaviridae (California encephalitis), can cause aseptic meningitis. These viruses are
most common in the summer and fall, when arthropods are most active.
128 Microbiology
Hepatitis viruses
 Signs and symptoms of all hepatitis viruses:
 Episodes of fever, jaundice, ↑ ALT and AST.
 Naked viruses (HAV and HEV) lack an envelope and are not destroyed by the gut: the
vowels hit your bowels.
 UW: The hepatitis B surface antigen of hepatitis B virus must coat the hepatitis D antigen
of hepatitis D virus before it can infect hepatocytes and multiply.
129 Microbiology
Extrahepatic manifestations of hepatitis B and C
Hepatitis A virus
 Transmission
 Occurs through the fecal-oral route.
 Common in areas with overcrowding and poor sanitation.
 Outbreaks frequently result from contaminated water or food with raw or
steamed shellfish (oysters) a common culprit in the United States.
 Symptoms:
 Onset is acute, and symptoms can include malaise, fatigue, anorexia, nausea,
vomiting, mild abdominal pain and an aversion to smoking.
 Hepatomegaly is commonly seen.
 AST and ALT spike early in the illness, followed by increases in bilirubin and
alkaline phosphatase.
 Markers:
 Anti-HAV (IgM)
 IgM antibody to HAV; best test to detect acute hepatitis A.
 Anti-HAV (IgG)
 IgG antibody indicates prior HAV infection and/or prior vaccination.
 Protects against reinfection.
 Close contacts of individuals with hepatitis A should promptly be given immune
globulin.
130 Microbiology
Hepatitis B virus:
 Morphology:
 Consists of a hexagonal protein core (capsid) covered with a lipid bilayer
envelope studded with proteins and carbohydrates.
 The HBV genome is a partially double-stranded circular DNA molecule
housed within the capsid.
 HBV DNA polymerase has DNA- and RNA-dependent activities.
 Upon entry into nucleus, the polymerase completes the partial dsDNA.
 Host RNA polymerase transcribes mRNA from viral DNA to make viral proteins.
 The DNA polymerase then reverse transcribes viral RNA to DNA, which is the
genome of the progeny virus.
 UW: HBV replicates via the following sequence:
 dsDNA  + RNA template  dsDNA progeny.
 Although it is a DNA virus, HBV replicates via reverse transcription.
131 Microbiology
Hepatitis B serologic markers

 HBsAg
 Antigen found on surface of HBV. Detectable during acute hepatitis B infection.
 Persistence after 6 months implies chronic infection.
 Anti-HBs
 Antibody to HBsAg; indicates immunity to hepatitis B due to vaccination or
recovery from
infection. Confers long-term immunity.
 HBcAg
 Antigen associated with core of HBV.
 Anti-HBc
 Antibody to HBcAg.
 IgM = acute/recent infection; may be the sole ⊕ marker of infection during
window period.
 IgG = prior exposure or chronic infection. Can be present in both acute and
chronic infection. Not present after vaccination.
 HBeAg
 Secreted by infected hepatocyte into circulation. Not part of mature HBV virion.
 Indicates active viral replication and therefore high transmissibility (infectivity)
and poorer prognosis.
 If a pregnant were HBeAg positive, her neonate's risk of infection would be 95%
(↑ vertical transmission).
 Because of this concern, the newborns of all mothers with active hepatitis B are
passively immunized at birth with hepatitis B immune globulin (HBIG), followed
by active immunization with recombinant HBV vaccine.
 Anti-HBe
 Antibody to HBeAg; indicates low viral replication and transmissibility.
132 Microbiology
Hepatitis C virus:
 Antigenic variation of HCV
 HCV lacks 3′-5′ exonuclease activity  no proofreading ability  variation in
antigenic structures of HCV envelope proteins.
 These variant strains differ primarily at hypervariable genomic regions such as
those with sequences coding for envelope glycoproteins.
 The continuous generation of novel envelope glycoproteins prevents infected
individuals from mounting an effective immune response.
 Host antibody production lags behind production of new mutant strains of HCV.
 The tremendous antigenic variety of HCV has significantly slowed efforts to
develop an effective vaccine.
133 Microbiology
134 Microbiology
HIV
 Diploid genome (2 molecules of RNA).

 The 3 structural genes (protein coded for):
 env (gp120 and gp41):
 Formed from cleavage of gp160 to form envelope glycoproteins.
 gp120—attachment to host CD4+ T cell.
 gp41—fusion and entry.
 Env gene mutations enable escape from host neutralizing antibodies.
 gag (p24 and p17)
 Capsid and matrix proteins, respectively.
 Pol
 Reverse transcriptase, aspartate protease, integrase.
 Reverse transcriptase synthesizes dsDNA from genomic RNA;
dsDNA integrates into host genome.
 Pol gene mutations are responsible for acquired resistance to HIV reverse
transcriptase inhibitors and HIV protease inhibitors.
 Virus binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection)
or CXCR4 on T cells (late infection).
 Homozygous CCR5 mutation = immunity. Heterozygous CCR5 mutation = slower
course.
135 Microbiology
UW: Only the env gene

polyprotein product is
glycosylated to gp160 and
proteolytically cleaved within
the endoplasmic reticulum and
Golgi apparatus to form the
envelope glycoproteins gpl20
and gp41.
HIV diagnosis
 Presumptive diagnosis:
 With HIV-1/2 Ag/ Ab immunoassays.
 These immunoassays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.
 Very high sensitivity/specificity.
 ⊕ Tests are confirmed with:
 HIV-1/2 Ab differentiation immunoassays which determine whether patient has
HIV-1 or HIV-2.
 If inconclusive differentiation assay, an HIV-1 nucleic acid amplification test
(NAAT) is performed
 If the NAAT is ⊝, patient had false positive initial Ag/Ab immunoassay.
 Viral load tests
 Determine the amount of viral RNA in the plasma.
 High viral load associated with poor prognosis.
 Also use viral load to monitor effect of drug therapy.
 Use HIV genotyping to determine appropriate therapy.
136 Microbiology
AIDS diagnosis
 ≤ 200 CD4+ cells/mm3 (normal: 500–1500 cells/mm3).
 HIV⊕ with AIDS-defining condition (eg, Pneumocystis pneumonia) or CD4+ percentage
< 14%.
 Western blot tests are no longer recommended by the CDC for confirmatory testing.
 HIV-1/2 Ag/Ab testing is not recommended in babies with suspected HIV due to maternally
transferred antibody. Use HIV viral load instead.
137 Microbiology
Time course of untreated HIV infection
Common diseases of HIV-positive adults

 As CD4+ cell count ↓, risks of reactivation of past infections (eg, TB, HSV, shingles),
dissemination of bacterial infections and fungal infections (eg, coccidioidomycosis), and
non-Hodgkin lymphomas ↑.
138 Microbiology
139 Microbiology
 UW: Ring-enhanced lesions with mass effect in HIV patient:

1. Toxoplasma:
 Multiple lesions; ttt with
pyrimethamine and sulfadizine.
2. Primary CNS lymphoma: (diffuse, large-cell
non-Hodgkin lymphoma of B-cell origin)
 Solitary large lesion.
 Caused by EBV and formed mainly by
B-lymphocytes.
 Diagnosis of PCNSL can be made by
positive EBV PCR analysis in the CSF.
 UW: HIV + pneumonia:

1. If normal CD4  str pneumonia.
2. If CD4 <200  PCP.
140 Microbiology
Pregnancy and HIV

 The risk of HIV infection occurring in an infant born to an HIV-positive mother who
received no prenatal antiretroviral therapy (ART) can be as high as 35%.
 ART during pregnancy reduces the risk of perinatal transmission to 1%-2%.
 All pregnant women with HIV should take ART, regardless of their CD4 cell count or
viral load.
 Triple combination therapy is recommended for HIV-positive pregnant women (as it is
for all HIV-positive adults) and most commonly has a backbone of 2
nucleoside/nucleotide reverse transcriptase inhibitors along with a third drug
(protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or integrase inhibitor).
 Drugs that are associated with a teratogenic risk (eg, efavirenz in first 8 weeks) or for
which there is insufficient evidence during pregnancy are to be avoided.
 ART should be continued as long as women are breastfeeding.
 Infants generally receive several weeks of prophylaxis (zidovudine).
Prions
 Prion diseases are caused by the conversion of a normal (predominantly α-helical)
protein termed prion protein (PrPc) to a β-pleated form (PrPsc), which is transmissible
via CNS-related tissue (iatrogenic CJD) or food contaminated by BSE-infected animal
products (variant CJD).
 PrPsc resists protease degradation and facilitates the conversion of still more PrPc to
PrPsc.
 Resistant to standard sterilizing procedures, including standard autoclaving.
 Accumulation of PrPsc results in spongiform encephalopathy and dementia, ataxia, and
death.
 Creutzfeldt-Jakob disease—rapidly progressive dementia, typically sporadic (some
familial forms).
 Bovine spongiform encephalopathy (BSE)—also known as ―mad cow disease.‖
 Kuru—acquired prion disease noted in tribal populations practicing human cannibalism.
141 Microbiology
Microbiology systems
Normal dominant flora:
Transmission of common infections
142 Microbiology
Bugs causing foodborne illness

 S aureus and B cereus food poisoning starts quickly and ends quickly.
Bugs causing diarrhea
143 Microbiology
144 Microbiology
Hepatic abscess
 Diagnosis:
 Fluid-filled cavity in the liver in conjunction with fevers, chills, and right upper
abdominal pain.
 Causes:
 In underdeveloped countries:
 Usually caused by parasitic infections (eg, Entamoeba histolytica,
echinococcal).
 In developed countries:
 Usually bacterial infection in about 80% of cases: Pyogenic bacteria can
gain access to the liver through the following routes:
 Biliary tract infection (eg, ascending cholangitis)  enteric gram-
negative bacilli
(eg, Escherichia coli, Klebsiella) and enterococci.
 Portal vein pyemia (bowel or peritoneal sources).
 Hepatic artery (systemic hematogenous seeding)  staph aureus.
 Direct invasion from an adjacent source (eg. peritonitis,
cholecystitis).
 Penetrating trauma or injury.
 The types of organisms causing a hepatic abscess depend on the route of
hepatic access.
145 Microbiology
Common causes of pneumonia
Aspiration syndromes:
146 Microbiology
Aspiration lung abscess:
 Cause:
 Commonly caused by anaerobic bacteria normally found in the oral cavity (eg,
Fusobacterium, Peptostreptococcus, Bacteroides).
 Site:
 As the right bronchus is straighter than the left, dependent areas of the right lung
tend to be affected.
 Therefore, if aspiration occurs in the upright position, an abscess in the basal
segment of the right lower lobe is likely.
 If aspiration occurs while supine, the posterior segment of the right upper lobe or
the superior segment of the right lower lobe is the most likely location.
 Symptoms:
 General: fever, malaise, weight loss, clubbing, and leukocytosis lasting a few
weeks.
 Specific: cough with copious production of greenish foul-smelling sputum.
 CXR:
 Cavitary lesion with air-fluid levels.
147 Microbiology
Common causes of meningitis
148 Microbiology
 Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults

of all ages.
 S. pneumoniae meningitis often follows a pulmonary infection or mild upper
respiratory infection.
 Alcoholics, sickle cell anemia patients, asplenic individuals, and those in
generally poor health are at greater risk for S pneumoniae meningitis.
149 Microbiology
CSF findings in meningitis
Treatment of meningitis:
 Meningococcocal meningitis  ceftriaxone, ciprofloxacin, rifampin.
 H influenza meningitis  rifampin.
150 Microbiology
Infections causing brain abscess

 Most commonly viridans streptococci and Staphylococcus aureus.
 If dental infection or extraction precedes abscess, oral anaerobes commonly involved.
 Multiple abscesses are usually from bacteremia.
 single lesions from contiguous sites:
 Otitis media and mastoiditis ↑ temporal lobe and cerebellum.
 Sinusitis or dental infection ↑ frontal lobe.
 Toxoplasma reactivation in AIDS.
Osteomyelitis
 Osteomyelitis is an infection of bone and bone marrow that occurs
by 1 of 3 mechanisms:
1. Hematogenous seeding due to an episode of bacteremia.
 Predominantly in children (particularly boys).
 Affects the metaphysis of long bones (tibia, fibula,
and femur).
 Symptoms are vague and high suspicious index is
required. Fever, malaise, bone pain and tenderness.
2. Spread from a contiguous focus of infection, as occurs in
an infected diabetic foot wound.
3. Direct inoculation of bone, such as with a compound
fracture.
 Diagnosis:
 Elevated C-reactive protein (CRP) and erythrocyte
sedimentation rate common but nonspecific.
 MRI is best for detecting acute infection and detailing anatomic involvement A.
 Radiographs are insensitive early but can be useful in chronic osteomyelitis B.
151 Microbiology
152 Microbiology
Urinary tract infections

 Primarily caused by ascension of microbes from urethra to bladder.
 Ten times more common in women (shorter urethras colonized by fecal flora).
 Males— infants with congenital defects, vesicoureteral reflux.
 Elderly—enlarged prostate.
 Other predisposing factors: obstruction, kidney surgery, catheterization, GU
malformation, diabetes, pregnancy.
 Cystitis (ascension to the urinary bladder)
 Presents with dysuria, frequency, urgency, suprapubic pain, and WBCs (but not
WBC casts) in urine.
 Pyelonephritis (ascension to the kidney)
 Presents with fever, chills, flank pain, costovertebral angle tenderness, hematuria,
and WBC casts.
UTI bugs
153 Microbiology
Common vaginal infections
154 Microbiology
 UW: Whiff test: "fishy" odor that becomes more prominent with addition of potassium
hydroxide.
 UW: Clue cells: are vaginal, squamous epithelial cells covered with multiple, small,
adherent G vaginalis organisms.
 UW: Sexual intercourse increases the risk for bacterial vaginosis, especially when an
individual has multiple partners.
 UW: Tichomoniasis findings:
 Vaginal burning itching, urinary discomfort.
 Yellow or green vaginal discharge, malodorous, frothy.
 Epithelial inflammation leading to:
 Erythematous vaginal mucosa.
 Cervical punctations (eg, strawberry cervix).
 Saline microscopy (eg, wet mount) of the discharge is the best diagnostic test
for.
155 Microbiology
 UW: Common triggers for Candida vaginitis include the following

 Antibiotic use  due to reduction of the lactobacilli population which facilitates
Candida overgrowth.
 High estrogen levels (eg, pregnancy).
 Systemic corticosteroid therapy.
 Uncontrolled diabetes mellitus.
 Any other cause of immunosuppression, including HIV.
ToRCHeS infections
 Microbes that may pass from mother to fetus. Transmission is transplacental in most
cases, or via delivery (especially HSV-2).
 Nonspecific signs common to many ToRCHeS infections include
 Hepatosplenomegaly, jaundice, thrombocytopenia, and growth retardation.
 Other important infectious agents include Streptococcus agalactiae (group B
streptococci), E coli,
and Listeria monocytogenes—all causes of meningitis in neonates.
 Parvovirus B19 causes hydrops fetalis.
 Triad of congenital toxoplasmosis:
 Hydrocephalus (enlarged ventricles).
 Intracranial calcifications (cotton-like white/yellow scars on the retina.)
 Chorioretinitis.
156 Microbiology
Sexually transmitted infections
157 Microbiology
158 Microbiology
159 Microbiology
160 Microbiology
Pelvic inflammatory disease

 Cause:
 Chlamydia trachomatis (subacute, often undiagnosed), most common bacterial
STI in the USA.
 Neisseria gonorrhoeae (acute).
 Presentation:
 Cervical motion tenderness (chandelier sign).
 Purulent cervical discharge A.
 PID may include salpingitis, endometritis, hydrosalpinx, and tubo-ovarian
abscess.
 Complications:
 Salpingitis is a risk factor for ectopic pregnancy, infertility, chronic pelvic pain,
and adhesions.
 Fitz-Hugh–Curtis syndrome
 Infection of the liver capsule and ―violin string‖ adhesions of peritoneum
to liver B.
161 Microbiology
Red rashes of childhood
162 Microbiology
Nosocomial infections
 E coli (UTI) and S aureus (wound infection) are the two most common causes.
163 Microbiology
Bugs affecting unvaccinated children
164 Microbiology
Bug hints (if all else fails)
Pasteurella wound infection has a

characteristic mouse-like odor
(indole-positive species).
165 Microbiology
Antimicrobials
166 Microbiology
Penicillin G, V
 Penicillin G (IV and IM form), penicillin V (oral). Prototype β-lactam antibiotics.
 Beta lactam ring is unique to penicillins and also present in (cephalosporins,
cabapenems, aztreonam).
 MECHANISM
 D-Ala-D-Ala structural analog. Bind penicillin-binding proteins
(transpeptidases).
 Block transpeptidase cross-linking of peptidoglycan in cell wall.
 Activate autolytic enzymes.
 Bactericidal.
 CLINICAL USE
 Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces).
 Also used for gram ⊝ cocci (mainly N meningitidis)
 Spirochetes (namely T pallidum).
 Penicillinase sensitive:
 Penicillinase is a beta lactamase enzyme present in the periplasm of the
gram negative bacteria; cabable of destructing the beta lactam ring.
 ADVERSE EFFECTS
 Hypersensitivity reactions
 Type I hypersensitivity: IgE-mediated, immediate, itching, urticaria,
bronchospasm, anaphylaxis.
 Maculopapular rash:
 Non-immediate reaction, type IV HS, days or weeks after starting
the drug.
 Most common with aminopenicillins.
 Maculopapules with absent of systemic signs like fever, wheezes,
joint pain.
 More common with viral infection. Amoxicillin given to EBV
pharyngitis  maculopapular rash.
 Serum sickness.
 Direct Coombs ⊕ hemolytic anemia. Considered type II hypersensitivity
reaction.
 Jarisch-Herxeimer reaction.
 Occurs with PCN for spirochetes ―syphilis‖  fever, chills, flushing two
hours after starting therapy.
167 Microbiology
 RESISTANCE
 Penicillinase (β-lactamase) in bacteria:
 Cleaves β-lactam ring.
 Present in (G –ve bacteria ―periplasm‖ & staph aureus ―secreted‖).
 β-lactamase inhibitors: clavulanic acid, sulbactam, tazobactam.
 Modifications in PBPs.
 Reduced bacterial cell penetration:
 Gram –ve bacteria: poor penetration (due to the presence of outer
membrane).
 Porins:
 Gram negative protein that transport chemicals like penicillins.
 Bacteria may decrease the number of porins.
 NB: probencid, which is a gout drug, can be given in conjugation with penicillin to boost
its level as it ↓ penecillins renal secretion.
168 Microbiology
Penicillinase-sensitive penicillins (Aminopenicillins)

 Amoxicillin (oral), ampicillin (IV).
 MECHANISM
 Same as penicillin. Penetrate porin channels of gram –ve bacteria  wider
spectrum (AMinoPenicillins are AMPed-up penicillin); penicillinase sensitive.
 Also combine with β-lactamase inhibitors (clavulanic acid & sulbuctam) to ↓
destruction by β-lactamase.
 Amoxicillin + clavulanic  resistant cases of otitis media.
 Ampicillin + sulbactam (IV)  surgical infections.
AmOxicillin has greater Oral bioavailability than ampicillin.
 CLINICAL USE
 Extended-spectrum penicillin—H influenzae, H pylori, E coli, Listeria
monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci. Coverage:
ampicillin/amoxicillin HHELPSS kill enterococci.
 Used in: URIs (G+ve & H. influenza), UTIs and colonic infections (E coli &
proteus & Enterococci & Salmonella), neonatal infections (E coli & Listeria).
 ADVERSE EFFECTS
 Hypersensitivity reactions; maculopapular rash; pseudomembranous colitis.
 MECHANISM OF RESISTANCE
 Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.
Penicillinase-resistant penicillins (antistaphylococcal penicillins)

 Dicloxacillin, nafcillin, oxacillin, methicillin.
 MECHANISM
 Same as penicillin. Narrow spectrum.
 Penicillinase resistant because bulky side chain R group blocks access of β-
lactamase to β-lactam ring.
 CLINICAL USE
 S aureus (except MRSA; resistant because of altered penicillin-binding protein
target site).
―Use naf (nafcillin) for staph.‖  mainly for skin infections (cellulitis &
impetigo).
 ADVERSE EFFECTS
 Hypersensitivity reactions.
 Interstitial nephritis.
169 Microbiology
Antipseudomonal penicillins
 Piperacillin, ticarcillin.
 MECHANISM
 Same as penicillin. Greater porin channel penetration than Aminopenicillin 
Extended spectrum.
 Susceptible to penicillinase.
 CLINICAL USE
 Most Gram +ve bacteria (not MRSA).
 More gram –ve coverage  Pseudomonas spp. and gram ⊝ rods.
 Use with β-lactamase inhibitors; (ticarcillin + clavulonate = Timentin),
(piperacillin + tazobactam = Zosyn).
 ADVERSE EFFECTS
 Hypersensitivity reactions.
β-lactamase inhibitors
 Include Clavulanic acid, Avibactam, Sulbactam, Tazobactam. CAST.
 Often added to penicillin antibiotics to protect the antibiotic from destruction by β-
lactamase (penicillinase).
170 Microbiology
Cephalosporins (generations I–V)

 MECHANISM
 β-lactam drugs that inhibit cell wall synthesis but are less susceptible to
penicillinases. Bactericidal.
 Organisms typically not covered by 1st–4th generation cephalosporins are
LAME:
Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
 As long as you increase the generation, you increase the gram –ve coverage and
decrease the gram +ve coverage.
 CLINICAL USE
 1st generation (cefazolin, cephalexin):
 Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae.—PEcK.
 Cefazolin used prior to surgery to prevent S aureus wound infections.
 2nd generation (cefaclor, cefoxitin, cefuroxime): Fake fox fur.
 Gram ⊕ cocci, H influenzae, Enterobacter aerogenes, Neisseria spp.,
Serratia
marcescens, Proteus mirabilis, E coli, Klebsiella pneumoniae. —HENS
PEcK.
 3rd generation (ceftriaxone, cefotaxime, cefpodoxime, ceftazidime)
 Serious gram ⊝ infections resistant to other β-lactams.
 Can cross blood-brain barrier.
 Ceftriaxone—meningitis ―good CNS penetration‖, gonorrhea,
disseminated Lyme disease.
 Ceftazidime—Pseudomonas.
 4th generation (cefepime):
 Gram ⊝ organisms, with ↑ activity against Pseudomonas and gram ⊕
organisms.
 5th generation (ceftaroline):
 Binds PBP2a (MRSA specific PBP).
 Broad gram ⊕ and gram ⊝ organism coverage.
 Unlike 1st–4th generation cephalosporins, ceftaroline covers Listeria,
MRSA, and Enterococcus faecalis.
 Does not cover Pseudomonas.
171 Microbiology
 ADVERSE EFFECTS
 Hypersensitivity reactions, autoimmune hemolytic anemia.
 Disulfiram-like reaction.
 Vitamin K deficiency:
 Antibiotics reduce vit k production from intestinal bacteria flora.
 Problem in patients taking warfarin.
 Hypoprothrombinemia:
 ↓ Epoxide reductase (as warfarin). In cefazolin and cefotetan.
 Low rate of cross reactivity even in penicillin-allergic patients.
 ↑ Nephrotoxicity of aminoglycosides.
 Structural change in penicillin-binding proteins (transpeptidases).
172 Microbiology
Carbapenems
 Imipenem, meropenem, ertapenem, doripenem.
 Resistant to cleavage by most of the β-lactamase. Drug of choice of ESBL bacteria.
 MECHANISM:
 Imipenem is a broad-spectrum, β-lactamase– resistant carbapenem.
 Always administered with cilastatin (inhibitor of renal dehydropeptidase
I) to ↓ inactivation of drug in renal tubules. With imipenem, ―the kill is
lastin’ with cilastatin.‖
 Meropenem has a more ↓ risk of seizures and stable to dehydropeptidase I than
imipenem.
 Newer carbapenems include ertapenem (limited Pseudomonas coverage) and
doripenem.
 CLINICAL USE:
 Gram ⊕ cocci, gram ⊝ rods, and anaerobes.
 Wide spectrum, but significant side effects limit use to life-threatening infections
or after other drugs have failed.
 ADVERSE EFFECTS:
 GI distress, skin rash.
 CNS toxicity (seizures due to inhibition of GABA receptors) at high plasma
levels especially with imipenem, lower risk with meropenem.
173 Microbiology
Monobactams (Aztreonam)
 It is a monocyclic β-lactams ―β-lactam ring not fused to another ring‖.
 MECHANISM:
 Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3
(only in G –ve bacteria.)
 Less susceptible to β-lactamases.
 Synergistic with aminoglycosides.
 No cross-allergenicity with penicillins.
 CLINICAL USE:
 ―Aminglycoside pretender‖  Gram ⊝ rods only—no activity against gram ⊕
rods or anaerobes.
 For penicillin-allergic patients and those with renal insufficiency who cannot
tolerate aminoglycosides.
 Usually nontoxic; occasional GI upset.
174 Microbiology
Vancomycin
 MECHANISM:
 Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell
wall precursors. ―Pay back 2 D-Alas (dollars) for vandalizing (vancomycin).
 Bactericidal against most bacteria (bacteriostatic against C diffcile).
 Not susceptible to β-lactamases.
 CLINICAL USE:
 Gram ⊕ bugs only—serious, multidrug-resistant organisms, including MRSA, S
epidermidis, sensitive Enterococcus species, and Clostridium diffcile (oral dose
for pseudomembranous colitis).
 Not effective against gram –ve bacteria as it has too large molecule that cannot
penetrate the outer membrane of the gram negative organisms.
 Well tolerated in general—but NOT trouble free. Nephrotoxicity, Ototoxicity,
Thrombophlebitis.
 Red man syndrome A
 Diffuse flushing of the whole body.
 Non-specific mast cell degranulation  histamine release.
 Treatment:
 Pretreatment with antihistamines and slow infusion rate.
 Can restart the medication.
 MECHANISM OF RESISTANCE:
 Occurs in bacteria (eg, Enterococcus) via amino acid modification of D-Ala-D-
Ala to D-Ala-D-Lac.
175 Microbiology
Protein synthesis inhibitors
176 Microbiology
Aminoglycosides
 Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin.
―Mean‖ (aminoglycoside) GNATS cannot kill anaerobes.
 MECHANISM:
 Irreversible inhibition of initiation complex through binding of the 30S subunit
causing misreading of mRNA.
 Also block translocation.
 Bactericidal (unique among protein synthesis inhibitors).
 Require O2 for uptake; therefore, ineffective against anaerobes.
 CLINICAL USE:
 Severe gram ⊝ rod infections.
 Synergistic with β-lactam antibiotics (rare to be used alone).
 Vancomycin + gentamycin for endocarditis.
 Ampicillin + gentamycin for neonatal meningitis.
 Neomycin for bowel surgery.
 Nephrotoxicity (ATN), Neuromuscular blockade (↓ Ach), Ototoxicity (especially
when used with loop diuretics). Teratogen.
 MECHANISM OF RESISTANCE:
 Bacterial transferase enzymes inactivate the drug by acetylation,
phosphorylation, or adenylation.
177 Microbiology
Tetracyclines
 Tetracycline, doxycycline, minocycline.
 MECHANISM
 Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA.
 PHARMACOKINETICS:
 Limited CNS penetration.
 Do not take tetracyclines with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-
containing preparations because divalent cations inhibit drugs’ absorption in the
gut.
 CLINICAL USE
 Borrelia burgdorferi, M pneumoniae.
 Drugs’ ability to accumulate intracellularly makes them very effective against
Rickettsia and Chlamydia.
 Also used to treat acne (cover propionebacterium acne within follicles).
 Doxycycline:
 Fecally eliminated and can be used in patients with renal failure.
 Effective against MRSA.
 Demeclocycline:
 Not used as antibiotic, ADH antagonist  given for SIADH.
 ADVERSE EFFECTS
 GI distress.
 Discoloration of teeth.
 Inhibition of bone growth in children.
 Photosensitivity.
 Contraindicated in pregnancy.
 ↓ Uptake or ↑ efflux out of bacterial cells by plasmid-encoded transport pumps.
Drugs with photosensitivity:
“SAT for photo”: Sulfonamides,

Aminoglycosides, Tetracycline.
178 Microbiology
Glycylcyclines
 Tigecycline.
 MECHANISM
 Tetracycline derivative.
 Binds to 30S, inhibiting protein synthesis. Generally bacteriostatic.
 CLINICAL USE
 Broad-spectrum anaerobic, gram ⊝, and gram ⊕ coverage.
 Multidrug-resistant (MRSA, VRE) organisms or infections requiring deep tissue
penetration.
 ADVERSE EFFECTS
 GI symptoms: nausea, vomiting.
Chloramphenicol
 MECHANISM
 Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
 CLINICAL USE
 Limited use owing to toxicities but often still used in developing countries
because of low cost.
 Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus
pneumoniae).
 Rocky Mountain spotted fever (Rickettsia rickettsii).
 Can be used in pregnancy instead of doxycycline.
 Only in the 1st and 2nd trimester. In 3rd trimester may cause gray baby
syndrome.
 ADVERSE EFFECTS
 Anemia (dose dependent), aplastic anemia (dose independent).
 Gray baby syndrome (in premature infants because they lack liver UDP-
glucuronyltransferase).
 Buildup of toxic metabolites of chloramphenicol.
 Vomiting + ashen grey color of the skin.
 Poor muscle tone + cyanosis + CV collapse.
 TTT: stop the drug, exchange transfusion, phenobarbital.
 Plasmid-encoded acetyltransferase inactivates the drug.
179 Microbiology
Gray baby syndrome  chloramphenicol.
Gray man syndrome  amiodarone.
Red man syndrome  vancomycin.
Clindamycin
 MECHANISM
 Blocks peptide transfer (translocation) at 50S ribosomal subunit ―same as
macrolides‖. Bacteriostatic.
 CLINICAL USE
 Anaerobic infections (eg, Bacteroides spp., Clostridium perfringens) in
aspiration pneumonia, lung abscesses, and oral infections. Treats anaerobic
infections above the diaphragm vs metronidazole (anaerobic infections below
diaphragm).
 Also effective against invasive group A streptococcal infection.
 Effective against MRSA.
 ADVERSE EFFECTS
 Pseudomembranous colitis (C diffcile overgrowth), fever, diarrhea.
 As macolides.
Oxazolidinones (Linezolid)
 MECHANISM
 Inhibit protein synthesis by binding to 50S subunit  preventing formation of the
initiation complex.
 CLINICAL USE
 Gram ⊕ species including MRSA and VRE.
 ADVERSE EFFECTS
 Bone marrow suppression (especially thrombocytopenia),
 Peripheral neuropathy.
 Weak MAOIs  Serotonin syndrome ―fever, confusion, agitation, hyperreflexia
when given with SSRIs‖.
 Point mutation of ribosomal RNA.
180 Microbiology
Macrolides
 Azithromycin, clarithromycin, erythromycin.
 MECHANISM
 Inhibit protein synthesis by blocking translocation (―macroslides‖); bind to the
23S rRNA of the
50S ribosomal subunit. Bacteriostatic.
Macrolides are
 CLINICAL USE (PUS)
concentrated inside
 Atypical pneumonias (Mycoplasma, Chlamydia,
the macrophages and
Legionella).
other cells  effective
 URI: str pneumonia, str pyogenes and B pertussis
against intracellular
 Streptococcal infections in patients allergic
organisms.
to penicillin.
 STIs (Chlamydia).
 Erythromycin: binds to the motilin receptors in the GIT  smooth muscle
contraction. Can be used in motility disorders (e.g, gastroparesis).
 ADVERSE EFFECTS
 MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT
interval, acute Cholestatic hepatitis (↑ ALP, mostly with azithromycin,
contraindicated in cholestatic liver disease), Rash, eOsinophilia.
 Clarithromycin and erythromycin inhibit cytochrome P-450  increases serum
concentration of theophylline, oral anticoagulants.
 Methylation of 23S rRNA-binding site prevents binding of drug.
181 Microbiology
Sulfonamides
 Sulfamethoxazole (SMX), sulfsoxazole, sulfadiazine.
 MECHANISM
 Inhibit dihydropteroate synthase, thus inhibiting folate synthesis.
 Bacteriostatic (bactericidal when combined with trimethoprim).
 CLINICAL USE
 Gram ⊕, gram ⊝, Nocardia. SMX for simple UTI.
 ADVERSE EFFECTS
 Hypersensitivity reactions, nephrotoxicity (tubulointerstitial nephritis),
photosensitivity, Stevens-Johnson syndrome.
 Hemolysis if G6PD deficient.
 Binds to albumin  displace other substances from albumin:
 Warfarin  ↑ INR in patients taking warfarin.
 Bilirubin  kernicterus in infants.
 Altered enzyme (bacterial dihydropteroate synthase).
 ↓ Uptake.
 ↑ PABA synthesis ―compete with sulfonamides for the dihydropteroate synthase‖.
182 Microbiology
Dapsone
 MECHANISM
 Similar to sulfonamides, but structurally distinct agent.
 CLINICAL USE
 Leprosy (lepromatous and tuberculoid),
 Pneumocystis jirovecii prophylaxis.
 ADVERSE EFFECTS
 Hemolysis if G6PD deficient.
Trimethoprim
 MECHANISM
 Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
 CLINICAL USE
 Used in combination with sulfonamides (trimethoprim-sulfamethoxazole
[TMPSMX]), causing sequential block of folate synthesis.
 Combination used for:
 UTIs, Shigella, Salmonella.
 Pneumocystis jirovecii pneumonia treatment and prophylaxis.
 Toxoplasmosis prophylaxis.
 ADVERSE EFFECTS
 Bone marrow suppression: Megaloblastic anemia, leukopenia, granulocytopenia.
TMP Treats Marrow Poorly.
 May alleviate with supplemental folinic acid:
 Converted to THF without using DHF reductase.
Streptogramins
 Quinopristin/ Dalfopristin (Synercid).
 Synthesized by the Streptomyces Virginia.
 Acts by binding the 23S portion of the 50S subunit of the ribosome.
 Uses: MRSA, VRE, staph and strept skin infections.
 SE: hepatotoxicity, pseudomembranous colitis.
183 Microbiology
Fluoroquinolones
 Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin,
enoxacin.
 MECHANISM
 Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase
IV.
 Bactericidal. Must not be taken with antacids.
 CLINICAL USE
 Gram ⊝ rods of urinary and GI tracts (including Pseudomonas), some gram ⊕
organisms.
 Otitis externa ―Cipro drops‖.
 ADVERSE EFFECTS
 GI upset, superinfections, skin rashes, headache, dizziness.
 Less commonly, can cause leg cramps and myalgias.
 Contraindicated in pregnant women, nursing mothers, and children < 18 years
old due to possible damage to cartilage. Fluoroquinolones hurt attachments to
your bones.
 May cause tendonitis or tendon rupture in people > 60 years old and in patients
taking prednisone.
 Some may prolong QT interval.
 Ciprofloxacin inhibits cytochrome P-450.
 Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance,
efflux pumps.
Daptomycin
 MECHANISM
 Lipopeptide that disrupts cell membranes of gram ⊕ cocci by creating
transmembrane channels.
 CLINICAL USE
 S aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE.
 Not used for pneumonia (avidly binds to and is inactivated by surfactant).
 ADVERSE EFFECTS
 Myopathy, rhabdomyolysis.
184 Microbiology
Metronidazole
 MECHANISM
 Forms toxic free radical metabolites in the bacterial cell that damage DNA
―DNA breakage‖  cell death ―bactericidal‖.
 Prodrug: must be reduced in order to be activated. Only anaerobic bacteria
capable of reduction.
 Antiprotozoal: as they lack mitochondria  aneorobic media favorable for
reduction of the drug.
 CLINICAL USE
 Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes
(Bacteroides,
C diffcile). GET GAP on the Metro with metronidazole!
 Can be used in place of amoxicillin in H pylori ―triple therapy‖ in case of
penicillin allergy.
 Treats anaerobic infection below the diaphragm vs clindamycin (anaerobic
infections above diaphragm).
 ADVERSE EFFECTS
 Disulfram-like reaction (severe flushing, tachycardia, hypotension) with
alcohol; headache,
 Metallic taste.
Polymyxins (Colistin “polymyxin E”, polymyxin B.)

 Mechanism:
 Cationic detergents (disrupt bacterial cell membrane).
 Cation polypeptides that bind to phospholipids on cell membrane of gram ⊝
bacteria.
 Disrupt cell membrane integrity  leakage of cellular components  cell death.
 Clinical use:
 Salvage therapy for multidrug-resistant gram ⊝ bacteria (eg, P aeruginosa, E
coli, K pneumoniae).
 Polymyxin B is a component of a triple antibiotic ointment used for superficial
skin infections.
 Adverse effects:
 Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias),
respiratory failure.
185 Microbiology
186 Microbiology
Antimycobacterial drugs
187 Microbiology
Rifamycins
 Rifampin, rifabutin.
 MECHANISM
 Inhibit DNA-dependent RNA
polymerase.
 CLINICAL USE
 Mycobacterium tuberculosis.
 Delay resistance to dapsone when used for leprosy.
 Used for meningococcal prophylaxis and chemoprophylaxis in contacts of
children with Haemophilus influenzae type B.
 ADVERSE EFFECTS
 Minor hepatotoxicity and drug interactions (↑ cytochrome P-450).
 Orange body fluids (nonhazardous side effect).
 Rifabutin favored over rifampin in patients with HIV infection due to less
cytochrome P-450 stimulation.
 Mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to
resistance.
188 Microbiology
Isoniazid
 MECHANISM
 ↓ Synthesis of mycolic acids.
 Bacterial catalase peroxidase (encoded by KatG) needed to convert INH to active
metabolite.
 CLINICAL USE
 Mycobacterium tuberculosis.
 The only agent used as solo prophylaxis against TB.
 Also used as monotherapy for latent TB.
 Different INH half-lives in fast vs slow acetylators.
 ADVERSE EFFECTS
 Hepatotoxicity, P-450 inhibition, drug-induced SLE, anion gap metabolic
acidosis.
 Vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia). Administer
with pyridoxine (B6).
INH Injures Neurons and Hepatocytes.
 Mutations leading to underexpression of KatG.
Pyrazinamide
 MECHANISM
 Mechanism uncertain.
 Pyrazinamide is a prodrug that is converted to the active compound pyrazinoic
acid.
 Works best at acidic pH (eg, in host phagolysosomes).
 CLINICAL USE: Mycobacterium tuberculosis.
 ADVERSE EFFECTS: Hyperuricemia, hepatotoxicity.
Ethambutol
 MECHANISM: ↓ carbohydrate polymerization of mycobacterium cell wall by blocking
arabinosyltransferase.
 CLINICAL USE Mycobacterium tuberculosis.
 ADVERSE EFFECTS: Optic neuropathy (red-green color blindness). Pronounce
―eyethambutol.‖
Streptomycin
 MECHANISM: Interferes with 30S component of ribosome.
 CLINICAL USE: Mycobacterium tuberculosis (2nd line).
 ADVERSE EFFECTS: Tinnitus, vertigo, ataxia, nephrotoxicity.
189 Microbiology
Antimicrobial prophylaxis
Prophylaxis in HIV patients
190 Microbiology
Treatment of highly resistant bacteria

 MRSA: vancomycin, daptomycin, linezolid, tigecycline, ceftaroline, doxycycline.
 VRE: linezolid and streptogramins (quinupristin, dalfopristin).
 Multidrug-resistant P aeruginosa, multidrug-resistant Acinetobacter baumannii:
polymyxins B and E (colistin).
191 Microbiology
Antifungal therapy
Amphotericin B
 MECHANISM
 Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of
electrolytes. Amphotericin ―tears‖ holes in the fungal membrane by forming
pores.
 CLINICAL USE
 Serious, systemic mycoses. Cryptococcus (amphotericin B with/without
flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma,
Candida, Mucor.
 Intrathecally for fungal meningitis.
 ADVERSE EFFECTS
 Fever/chills (―shake and bake‖), hypotension, nephrotoxicity, arrhythmias,
anemia, IV phlebitis (―amphoterrible‖).
 Hydration ↓ nephrotoxicity. Liposomal amphotericin ↓ toxicity.
 Supplement K+ and Mg2+ because of altered renal tubule permeability.
Nystatin
 MECHANISM
 Same as amphotericin B. Topical use only as too toxic for systemic use.
 CLINICAL USE
 ―Swish and swallow‖ for oral candidiasis (thrush).
 Topical for diaper rash or vaginal candidiasis.
192 Microbiology
Flucytosine
 MECHANISM
 Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine
deaminase.
 CLINICAL USE
 Systemic fungal infections (especially meningitis caused by Cryptococcus) in
combination with amphotericin B.
 ADVERSE EFFECTS
 Bone marrow suppression.
Azoles
 Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole,
isavuconazole.
 MECHANISM
 Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450
enzyme that converts lanosterol to ergosterol.
 CLINICAL USE
 Local and less serious systemic mycoses.
 Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients
and candidal infections of all types.
 Itraconazole for Blastomyces, Coccidioides, Histoplasma.
 Clotrimazole and miconazole for topical fungal infections.
 Voriconazole for Aspergillus and some Candida.
 Isavuconazole for serious Aspergillus and Mucorales infections.
 ADVERSE EFFECTS
 Testosterone synthesis inhibition (gynecomastia, especially with ketoconazole).
 Liver dysfunction (inhibits cytochrome P-450).
Terbinafne
 MECHANISM: Inhibits the fungal enzyme squalene epoxidase.
 CLINICAL USE: Dermatophytoses (especially onychomycosis—fungal infection of fnger
or toe nails).
 ADVERSE EFFECTS: GI upset, headaches, hepatotoxicity, taste disturbance.
Echinocandins
 Anidulafungin, caspofungin, micafungin.
 MECHANISM: Inhibit cell wall synthesis by inhibiting synthesis of β-glucan.
 CLINICAL USE: Invasive aspergillosis, Candida.
 ADVERSE EFFECTS: GI upset, flushing (by histamine release).
193 Microbiology
Griseofulvin
 MECHANISM:
 Interferes with microtubule function; disrupts mitosis. Deposits in keratin-
containing tissues (eg, nails).
 CLINICAL USE: Oral treatment of superficial infections; inhibits growth of dermatophytes
(tinea, ringworm).
 ADVERSE EFFECTS: Teratogenic, carcinogenic, confusion, headaches, disulfram-like
reaction, q cytochrome P-450 and warfarin metabolism.
Antiprotozoan therapy
 Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei),
nifurtimox (T cruzi), sodium stibogluconate (leishmaniasis).
Anti-mite/louse therapy
 Permethrin (neuronal membrane depolarization via Na+ channels), malathion
(acetylcholinesterase inhibitor), lindane (blocks GABA channels ↑ neurotoxicity).
 Used to treat scabies (Sarcoptes scabiei) and lice (Pediculus and Pthirus).
 Treat PML (Pesty Mites and Lice) with PML (Permethrin, Malathion, Lindane),
because they NAG you (Na, AChE, GABA blockade).
Chloroquine
 MECHANISM:
 Blocks detoxification of heme into hemozoin.
 Heme accumulates and is toxic to plasmodia.
 CLINICAL USE:
 Treatment of plasmodial species other than P falciparum (frequency of
resistance in P falciparum is too high). Treat P falciparum with
artemether/lumefantrine or atovaquone/proguanil.
 For life-threatening malaria, use quinidine in US (quinine elsewhere) or
artesunate.
 Mechanism of resistance:
 Due to membrane pump that ↓ intracellular concentration of drug.
 ADVERSE EFFECTS
 Retinopathy; pruritus (especially in dark-skinned individuals).
194 Microbiology
Antihelminthic therapy
 Mebendazole (microtubule inhibitor), pyrantel pamoate, ivermectin, diethylcarbamazine,
praziquantel.
Antiviral therapy
195 Microbiology
Oseltamivir, zanamivir
 MECHANISM
 Inhibit influenza neuraminidase  ↓ release of progeny virus.
 CLINICAL USE
 Treatment and prevention of both influenza A and B.
 Beginning therapy within 48 hours of symptom onset may shorten duration of
illness.
Acyclovir, famciclovir, valacyclovir

 MECHANISM
 Guanosine analogs.
 Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in
uninfected cells  few adverse effects.
 Triphosphate formed by cellular enzymes.
 Preferentially inhibit viral DNA polymerase by chain termination.
 CLINICAL USE
 HSV and VZV.
 Weak activity against EBV. No activity against CMV.
 Used for HSV induced mucocutaneous and genital lesions as well as for
encephalitis.
 Prophylaxis in immunocompromised patients.
 No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug of acyclovir,
has better oral bioavailability.
 For herpes zoster, use famciclovir.
196 Microbiology
 ADVERSE EFFECTS
 Obstructive crystalline nephropathy and acute renal failure if not adequately
hydrated.
 Mutated viral thymidine kinase.
Ganciclovir
 MECHANISM
 5′-monophosphate formed by a CMV viral kinase. Guanosine analog.
 Triphosphate formed by cellular kinases.
 Preferentially inhibits viral DNA polymerase.
 CLINICAL USE
 CMV, especially in immunocompromised patients.
 Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability.
 ADVERSE EFFECTS
 Bone marrow suppression (leukopenia, neutropenia, thrombocytopenia), renal
toxicity. More toxic to host enzymes than acyclovir.
 Mutated viral kinase.
Foscarnet
 MECHANISM
 Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor.
 Binds to pyrophosphate-binding site of enzyme.
 Does not require any kinase activation.
Foscarnet = pyrofosphate analog.
 CLINICAL USE
 CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-
resistant HSV.
 ADVERSE EFFECTS
 Nephrotoxicity, electrolyte abnormalities (hypo- or hypercalcemia, hypo- or
hyperphosphatemia, hypokalemia, hypomagnesemia) can lead to seizures.
 Mutated DNA polymerase.
197 Microbiology
Cidofovir
 MECHANISM
 Preferentially inhibits viral DNA polymerase. Does not require phosphorylation
by viral kinase.
 CLINICAL USE
 CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long
half-life.
 ADVERSE EFFECTS
 Nephrotoxicity (coadminister with probenecid and IV saline to r toxicity).
HIV therapy
 Highly active antiretroviral therapy (HAART): often initiated at the time of HIV
diagnosis.
 Strongest indication for patients presenting with:
 AIDS-defining illness.
 Low CD4+ cell counts (< 500 cells/mm3).
 High viral load.
 Regimen consists of 3 drugs to prevent resistance:
 2 NRTIs and preferably an integrase inhibitor.
NRTIs
 Drugs:
 Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC)
Stavudine (d4T) Tenofovir (TDF) Zidovudine (ZDV, formerly AZT)
 Mechanism:
 Competitively inhibit nucleotide binding to reverse transcriptase and terminate the
DNA chain (lack a 3′ OH group).
 Tenofovir is a nucleoTide; the others are nucleosides.
 All need to be phosphorylated to be active.
 ZDV can be used for general prophylaxis and during pregnancy to ↓ risk of fetal
transmission.
 Have you dined (vudine) with my nuclear (nucleosides) family?
 Toxicity:
 Bone marrow suppression (can be reversed with granulocyte colony-stimulating
factor [G-CSF] and erythropoietin), peripheral neuropathy, lactic acidosis
(nucleosides), anemia (ZDV), pancreatitis (didanosine).
 Abacavir contraindicated if patient has HLA-B*5701 mutation due to ↑ risk of
hypersensitivity.
198 Microbiology
NNRTIs
 Drugs:
 Delavirdine, Efavirenz, Nevirapine.
 Mechanism:
 Bind to reverse transcriptase at site different from NRTIs.
 Do not require phosphorylation to be active or compete with nucleotides.
 Toxicity:
 Rash and hepatotoxicity are common to all NNRTIs.
 Vivid dreams and CNS symptoms are common with efavirenz.
 Delavirdine and efavirenz are contraindicated in pregnancy.
Protease inhibitors
 Drugs:
 Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir,
Saquinavir.
Navir (never) tease a protease.
 Mechanism:
 Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the
polypeptide products of HIV mRNA into their functional parts.
 Thus, protease inhibitors prevent maturation of new viruses.
 Ritonavir can ―boost‖ other drug concentrations by inhibiting cytochrome P-450.
 Toxicity:
 Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy (Cushing-like
syndrome).
 Nephropathy, hematuria, thrombocytopenia (indinavir).
 Rifampin (potent CYP/UGT inducer) reduces protease inhibitor concentrations;
use rifabutin instead.
Integrase inhibitors
 Drugs:
 Raltegravir, Elvitegravir, Dolutegravir.
 Inhibits HIV genome integration into host cell chromosome by reversibly
inhibiting HIV integrase.
 Toxicity:
 ↑ Creatine kinase.
Fusion inhibitors
 Enfuvirtide
 Binds gp41, inhibiting viral entry.
 Skin reaction at injection sites.
199 Microbiology
 Enfuvirtide
 Inhibits fusion.
 Maraviroc
 Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.
 Maraviroc inhibits docking.
Interferons
 MECHANISM:
 Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide
range of antiviral and antitumoral properties.
 CLINICAL USE
 IFN-α: chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia,
condyloma acuminatum, renal cell carcinoma, malignant melanoma.
 IFN-β: multiple sclerosis.
 IFN-γ: chronic granulomatous disease.
 ADVERSE EFFECTS
 Flu-like symptoms, depression, neutropenia, myopathy.
200 Microbiology
Hepatitis C therapy
 Chronic HCV infection is treated with different combinations of the following drugs;
none is approved as monotherapy.
 Ribavirin also used to treat RSV (palivizumab preferred in children).
Ledipasvir
 Viral phosphoprotein (NS5A) inhibitor; NS5A plays important role in replication.
Ribavirin
 Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine

monophosphate dehydrogenase.
 Used in chronic HCV; also used in RSV (palivizumab preferred in children).
 Adverse effects: hemolytic anemia; severe teratogen.
Sofosbuvir
 Inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator.
 Chronic HCV in combination with ribavirin, simeprevir, ledipasvir (NS5A inhibitor), +/–
peginterferon alfa.
 Do not use as monotherapy.
 Adverse effects: fatigue, headache, nausea.
201 Microbiology
Simeprevir
 HCV protease inhibitor (NS3/4A); prevents viral replication.
 Used in: chronic HCV in combination with ledipasvir (NS5A inhibitor).
 Do not use as monotherapy.
 Adverse effects: photosensitivity reactions, rash.
Disinfection and sterilization

 Goals include:
 Reduction of pathogenic organism counts to safe levels (disinfection).
 Inactivation of self-propagating biological entities (sterilization).
 Autoclave:
 Pressurized steam at > 120°C. May be sporicidal.
 May not reliably inactivate prions.
 Alcohols (ethanol and isopropanol)
 Denature proteins and disrupt cell membranes.
 Disorganizing the lipid structure in membranes, causing them to be leaky,
and by denaturing cellular proteins.
 Alcohols require the presence of water for maximal activity and are most effective
at 60%-90% concentration.
 They are rapidly bactericidal and also tuberculocidal, fungicidal, and virucidal,
but do not destroy bacterial spores.
 Used to clean the skin before immunization or venipuncture and to disinfect
external surfaces of equipment.
 Chlorhexidine
 Denatures proteins and disrupts cell membranes.
 Not sporicidal.
 In combination with 70% alcohol, it is the antiseptic of choice for many surgical
and percutaneous procedures.
 Its use is contraindicated in neurologic, otologic, and ophthalmologic procedures
due to neurotoxicity.
 Hydrogen peroxide
 Free radical oxidation.
 Sporicidal.
 It is excellent at disinfecting inanimate objects but is less effective when used on
organic materials.
 Often used for skin cleansing and wound debridement due to its effervescent
quality.
202 Microbiology
 Iodine and iodophors

 Halogenation of DNA, RNA, and proteins.
 May be sporicidal.
 Less effective than chlorhexidine-alcohol and cause more skin irritation and
toxicity.
 Chlorine
 Oxidizes and denatures proteins. Sporicidal.
 Quaternary amines
 Impair permeability of cell membranes. Not sporicidal.
203 Microbiology
UW: Central venous catheter infections:

 Most common organisms:
1. coagulase-negative staphylococci (staph epidermitis).
2. Staphylococcus auraus.
 Recommendations to reduce CVC infections:
1. Hand hygiene with an alcohol sanitizer or antimicrobial soap prior

to donning sterile gloves. “most important”
CDC 2. Maximal barrier precautions during insertion of the central line
(surgical mask, sterile gloves, long-sleeved surgical gown, and a
recommended to
large sterile sheet drape).
prevent CVC
3. Chlorhexidine for skin disinfection.
infection 4. Avoidance of the femoral insertion site.
5. Removal of the catheter when no longer needed.
– Topical antimicrobial ointments.

Not shown to
– Oral or parenteral antibiotics.
prevent – Catheter replacement at scheduled intervals, or at any time when there is
CVC infection no evidence of infection.
 UW: Contact precautions for C. difficile infection:

1. Handwashing with soap and water (alcohol-based hand sanitizers do not
kill the spores).
2. Gown for any patient contact.
3. Nonsterile gloves that should be changed after contact with contaminated
secretions.
4. A dedicated stethoscope and blood pressure cuff should be left in the
patient's room.
204 Microbiology
 UW: Droplet infection:

1. Pathogens > 5 micron  remain suspended in air for limited periods only
(eg, Neisseria meningitides, influenza, Bordetella pertussis, Mycoplasma
pneumoniae, respiratory syncytial virus).
2. Healthcare workers need to wear a simple facemask when within 6-10 feet
of affected patients (droplet precautions).
 UW: Airborne precautions:
1. Isolated room with negative pressure ventilation.
2. Respirator mask with filtering capacity (eg, N95 mask) to avoid potential
exposure to aerosolized particles (<5 microns) that can remain suspended
in air for extended periods.
3. Gloves and gowns are not needed.
4. Airborne precautions are required for certain bacteria (eg. tuberculosis)
and viruses (eg,
varicella).
 Droplet infection  use simple facemask.

 Airborne infection  use respirator mask.
 NB: Sterile gloves generally are used for minor procedures or surgeries but are
not required in patients with contact precautions.
205 Microbiology
Contact Precautions
Contact Droplet Airborne

N. meningitidis, Mumps,
Pertussis, Pulmonary Tuberculosis,
Organism MRSA, C. difficile, lice,
Norovirus, vomiting, Measles, Chickenpox,
Precautions scabies
Influenza, Strep disseminated zoster
pyogenes (GAS)
Toxic shock, >2 of the
Fever, weight loss + cough,
Symptomatic Draining wound, following: stiff
high TB risk, disseminated
Precautions diarrhea, infestation neck, fever, headache,
rash + fever
malaise, acute cough
Private Room Preferred Preferred YES
Negative Pressure
No No YES
Room
Protective Gown + Gloves + Surgical Gown + Gloves + N95
Gown + Gloves
Equipment Mask Mask
206 Microbiology
Antimicrobials to avoid in pregnancy
207 Microbiology
208 Microbiology

Microbiology, Usmle Endpoint

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USMLE ENDPOINT Dr Ahmed Shebl

STRUCTURE CHEMICAL COMPOSITION FUNCTION

Capsule  Organized, discrete  Protects against

Cell wall  Peptidoglycan is a sugar  Net-like structure gives rigid

 UW: Bacterial sepsis is caused by:

Properties of growth media

Indicator (diﬀerential) media

Special culture requirements

Encapsulated bacteria vaccines

In vivo biofilm producing bacteria

Bacterial virulence factors

Type III secretion system

Main features of exotoxins and endotoxins

Bugs with exotoxins

Gram-positive lab algorithm

Gram-positive cocci antibiotic tests

 Rapid-onset food poisoning (enterotoxins).

3. MRSA (methicillin-resistant S aureus) infection:

 UW: S aureus is the most common cause of tricuspid endocarditis in intravenous

UW: Secondary bacterial pneumonia after influenza A virus:

 Patients older than 65 are particularly prone.

Initial empiric treatment of coagulase-negative

If susceptibility results indicate a methicillin-

Viridans group streptococci

Streptococcus pyogenes (group A streptococci)

Impetigo is caused by Staph

Streptococcus agalactiae (group B streptococci)

Enterococci have both intrinsic (beta-lactams, macrolides, aminoglycosides, trimethoprim-

 Edema Factor: acts as adenylate cyclase, increases cAMP, causes fluid to

Clostridia (with exotoxins)

 Treatment of C. Difficile infection:

 It is an oral drug with bacteriocidal activity, minimal systemic absorption,

UW: Tetrodotoxin poisoning (due to contaminated pufferfish ingestion) leads to inhibition

 Treatment of an acute C. diphthariae infection: requires administration of (in order of

 Sulfur granules: yellow aggregations of organisms bound together by proteins (Sulfur

Primary and secondary tuberculosis

 PPD ⊕ if current infection or past exposure.

UW: Isoniazid is an antimycobacterial agent that specifically inhibits the synthesis of

Leprosy (Hansen disease)

 Macrophage signaling to kill M leprae is limited, leading to

Gram-negative lab algorithm

Lactose-fermenting enteric bacteria

6- Fitz-Hugh-Curtis Syndrome (FHC):

7- Disseminated gonococcal infection (DGI)

Treatment of N gonorrhea infection:

UW: Ruptured ectopic pregnancy:

 Causes abdominal pain, vaginal bleeding and hemodynamic instability.

UW: Diagnosis of Neisseria Gonorrhea:

o Pharynx  blood  choroid plexus  meninges.

 PSEUDOMONAS is associated with:

Both Staphylococcus aureus and Salmonella are common causes of osteomyelitis in

 Transmitted via ingestion of contaminated water or uncooked food (eg, raw

A Key Lyme pie to the FACE:

 Stage 1 (early localized)

Rapid plasma reagin test:

 Pelvic inflammatory disease (PID) is most frequently caused by Neisseria gonorrhoaae

Chlamydia trachomatis serotypes

Types L1, L2, and L3  Lymphogranuloma venereum

Rickettsial diseases and vector-borne illnesses