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Principles of Antimicrobial Use

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40 views5 pages

Principles of Antimicrobial Use

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gayleteguichan19
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Principles of Antimicrobial Use

- development of antimicrobial therapy is considered by many to be one of the most important advances
in the history of the medicine
- efficacy and relative safety of these drugs has led to their widespread use and overuse
NOTE: ( persons take antibiotics immediately even though it is not needed, leading to overuse and
increase incidence for the ability of microorganisms to alter microbial flora, leading to antibiotic resistant
microorganisms)
- because of their ability to alter microbial flora and lead to antibiotic-resistant microorganisms, they are
fundamentally different from other types of drugs

I. Major historical events leading to the development of antimicrobial therapy

 History of Antimicrobial Therapy


- early 17th century: first recorded successful use of antimicrobial therapy involving the use of an extract
from cinchoma bark for the treatment of malaria
- 1909: Paul Ehrlich quest for a "magic bullet" that would bind specifically to a particular sites on parasitic
organisms leads to an arsenic derivative, salvarsan, with modest activity against syphilis. He suggested
that antimicrobial drugs would be most useful if the sites of an action were not present in the organs and
tissues of the human host
- 1929: Alexander Fleming’s penicillin, but it was only in 1940 when Florey and Chain first used penicillin
-1935: discovery of protonsil, a forerunner of sulfonamides
- the term antibiotic refers to substances produced by microorganims to supress growth of other
microorganisms. They are discovered from other antimicrobial agents; broader in meaning, encompasses
drugs that are synthesized in the lab
NOTE: Many agents are semi synthetic

 Antimicrobial agents can be classified into major groups


1. antibiotics that inhibit damage to peptidoglycan cell wall of microorganisms
2. inhibition of synthesis or damage to the cytoplasmic membrane of microorganism
3. modification in synthesis of nucleic acid
4. modification of protein synthesis
5. modification of energy

 Agents that inhibit synthesis of cell wall


1. B-lactams- PEN cephalosporins, monobactam
2. Vancomycin- fungi wall is damaged by polyene and azole

 Inhibitors of cytoplasmic membrane


1. polymyxins
2. daptomycin

 Inhibitors of nucleic acid synthesis


1. quinolone- inhibits DNA gyrase
2. rifampicin- RNS polymerase inhibitory

 Inhibitors of protein synthesis


1. aminoglycosides
2. tetracyclines
3. clindamycin
4. linezolid
 Drug selection for individual patient
- choose an antibiotic depending on their mechanism of action

 Factors to consider when selecting antimicrobial agents fot therapy in patient


1, is it necessary?
2. identification of the pathogen
3. empiric versus directed therapy
4. susceptibility of infecting microorganism
5. need for bactericidal versus bacteriostatic agent
6. pharmacokinetic and pharmacodynamic factors
7. anatomical site of infection
8. cost
9. toxicity

HOST FACTORS
-allergy history
-age
-renal function
-hepatic function
-pregnancy status
-genetic and metabolic abnormalities
-host defenses, WBC function

*NEED FOR COMBINATION THERAPY


* ANTIBIOTIC RESISTANCE CONCERNS

 IS AN ANTIMICROBIAL INDICATED?
- antibiotics are often administered because of culture isolation of an organisms that is colonizing an
anatomical site and not causing an infection

 How to do culture isolation?


- get a sample from a part of your body that you think have signs of infection, such as abscess. Then let it
grow in culture medium. You can take specimen from blood, urine, and secretions. Then spread it on the
culture media using cotton bud, then let it grow. Take a certain antibiotic and put it in the culture media,
then see if there is clearing, to see if the bacteria is intermediate or sensitive or resistant to the given
antibiotic.
NOTE: clinician should resist temptation to begin antimicrobial therapy unless there is a reasonable
probability that bacterial infection is present
example:
Bacterial meningitis - therapy should be started without delay even when presence of bacteria is
uncertain. Use broad spectrum agents.

Empiric therapy - giving antibiotic without knowing yet the causative organism, or the culture and
sensitivity result
Directed therapy- you already know the causative microorganism and that it is sensitive to a particular
antibiotic
Prophylactic therapy - intended to prevent illness in someone at risk of infection

IDENTIFICATION OF PATHOGEN
- an attempt should be made to identify pathogen before giving treatment.
Gram staining- fastest, simplest, and most inexpensive method to identify bacteria and fungi. Results can
be used to guide the initial antimicrobial choice. Most body fluid that is normally sterile should be gram
stained. Stains of wound exudates, sputum, and fecal material.
Sterile fluids in the body: CSF, tears, seminal fluid

 EMPIRIC versus DIRECTED THERAPY


- for certain infections (Cellulitis, otitis media, and sinusitis) its not possible to obtain specimen for gram
staining and culture.
NOTE: In pneumonia, yield of culture material is low
- when it is not possible to obtain specimen, antimicrobial therapy is often started empirically.
- knowledge of the antimicrobial spectrum of an agent and the likely pathogens causing infection of an
agent at a particular anatomical site can help.

NOTE: STAPHYLOCOCCUS and STREPTOCOCCUS ARE GRAM POSITIVE


- use of agents with broad sensitivity activity probably disturbs normal bacterial flora to a greater degree
than narrow spectrum therapy and may promote the development of an antibiotic resistant pathogen
- setting in which an infection occurs should be considered when selecting empiric therapy
NOTE: nosocomial infections- caused by antibiotic resistant bacteria in the hospital
- knowledge of these local resistance patterns is very helpful in directing empiric therapy
NOTE: Broad activity antibiotics causes more antibiotic resistant bacteria or strains or pathogen

 NEED OF BACTERICIDAL VERSUS BACTERIOSTATIC AGENT


- antimicrobial agents can be bactericidal ( organism are killed) or bacteriostatic ( organisms are
prevented from growing)
- bacteriostatic agent is adequate in uncomplicated infections because the host defenses will help
eradicate the microorganism

Pneumococcal pneumonia- you can use bacteriostatic agents to suppress multiplication of pneumococci

 Under what conditions are bacteriostatic become bactericidal


- if you increase drug dosage of bacteriostatic
-dependent on type of bacteria you are targeting

immunocompromised- not good working immune system

Neutropenic individual - bacteriostatic agent might prove ineffective and bactericidal agent would be
necessary.
NOTE: The status of the host influences whether a bactericidal or bacteriostatic agent is selected. Because
the site of infection influences the ability of certain host defenses to effectively contend with microbes,
bactericidal agents are required for management of infections in areas "protected" from host immune
responses ( endocarditic vegetation and CSF)

Endocarditis- treatment with bacteriostatic antibiotics (tetracycline, erythromycine) is associated with an


unacceptable high failure rate in contrast with cure rates

Meningitis- concentrations of an antimicrobial agents 8 to 10 fold greater than the MBC ( Minimum
Bactericidal Concentration) must be achieved in spinal fluid of the patient

NOTE: antimicrobial agents are usually administered by oral, IM, IV


- most agents reach peak serum concentrations 1 to 2 hours after oral administrations. However, peak
concentrations may be delayed:
a. if drugs are ingested with foods or
b. in patients with delayed intestinal transit (diabetic)

NOTE: peak plasma concentrations is reached in 0.5 to 1 hour after IM injections and at the end of the IV
infusion of 20 to 30 minutes
- antimicrobial agents vary widely in their oral bioavailability

- Some agents mare almost completely absorbed orally:


a. trimethroprim/ sulfamethoxazole
b fluoroquinolones
c. rifampicin
d. metronidazole

NOTE: Life threatening infections are treated initially with IV agents

- parenteral therapy ensures adequate serum levels and for many agents, higher drug levels can be
achieved when IV administered.

 The amount of antimicrobial agent that reaches the extravascular tissues and fluids, where the
infection is usually present depends on:
- concentration gradient between plasma and target tissue
- degree of drug binding to tissues
- molecular size
- degree of ionization and lipid solubility of the drug
- rate of elimination or metabolism

NOTE: certain antibiotics (fluoroquinolones and aminoglycosides) kill bacteria faster at higher
concentrations, a property called concentration-dependent killing.

Post antibiotic effect- agents continue to inhibit growth of bacterial foe several hours after the
concentrations of the drug fall below MIC in the serum.

NOTE: Beta-lactams are time dependent antibiotics. They do not exhibit concentration dependent killing
nor do they have prolonged post antibiotic effect.

NOTE: TIME DEPENDENT AND CONCENTRATION DEPENDENT DRUG

Anatomical sites of infection


- the site of infection often influences not only the agents used but for also dose, route, and duration of
administration
- desired peak concentration of the drugs at the site of infection should be at least 4x at the MIC ( minimum
inhibitory concentration)
- however, if host defenses are adequate, peak concentrations may be much lower and even be equal to
the MIC and still be effective, when host defenses are absent or inoperative, peak concentrations 8 to 16
fold greater than the MIC may be required

 Most antimicrobial agents readily enter most body tissues and compartments except for the:
a. CSF
b. brain
c. eye
d. prostate
-By using the parenteral route, concentrations adequate to treat infections of the pleural, pericardial, and
joint spaces can be obtained

NOTE: leukocytes are agents of the body that fights infection.

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