Pneumonia historical classification:

Typically classified as
1)community-acquired (CAP)
2)hospital-acquired (HAP), or
3)ventilator-associated (VAP)
4)health care–associated pneumonia (HCAP)

Health care–associated pneumonia (HCAP) This category was meant to

encompass those cases of CAP that were caused by multidrug-resistant (MDR)
pathogens typically associated with HAP.
At least two, if not three, risk factors are required before the probability of
drug resistant pathogens is sufficient to influence initial empirical
broadspectrum antibiotic therapy.

Risk Factors for Pathogens Resistant to Usual Therapy for Community-Acquired

Pneumonia:

PATHOPHYSIOLOGY:
 Pneumonia results from the proliferation of microbial pathogens at the
alveolar level and the host’s response to those pathogens.
Microorganisms gain access to the lower respiratory tract in several ways. The
most common is by aspiration from the oropharynx.
Small-volume aspiration occurs frequently during sleep (especially in the
elderly) and in patients with decreased levels of consciousness.
Rarely, pneumonia occurs via hematogenous spread (e.g., from tricuspid
endocarditis) or by contiguous extension from an infected pleural or
mediastinal space.

1. Mechanical host defences of lung >>

Clinical syndrome of pneumonia

when the capacity of the alveolar macrophages to ingest or kill the
microorganisms is exceeded than clinical pneumonia become manifest.
alveolar macrophages initiate the inflammatory response to bolster (tool
providing respiratory support) lower respiratory tract defenses.
host inflammatory response, rather than proliferation of microorganisms,
triggers the clinical syndrome of pneumonia.
Chemokines, such as interleukin 8 and granulocyte colony-stimulating cause
release of neutrophils attraction to the lung, producing both peripheral
leukocytosis and increased purulent secretions, alveolar capillary leak.
Inflammatory mediators released by macrophages and the newly recruited
neutrophils create an alveolar capillary leak equivalent to that seen in acute
respiratory distress syndrome, although in pneumonia this leak is localized
(at least initially)

Clinical features of pneumonia and their Patho physiology

Fever release of inflammatory mediators, such as interleukin 1 and tumor
necrosis factor, results in fever.
Hemoptysis: erythrocytes can cross the alveolar–capillary membrane, with
consequent hemoptysis.(due to leak)

Rales: The capillary leak results in a radiographic infiltrate and rales

detectable on auscultation, and hypoxemia results from alveolar filling.

Severe hypoxemia; some bacterial pathogens appear to interfere with the

hypoxemic vasoconstriction that would normally occur with fluid-filled
alveoli, and this interference can result in severe hypoxemia.

Respiratory alkalosis; Increased respiratory drive in the systemic

inflammatory response syndrome (Chap. 297) leads to respiratory alkalosis.

Dyspnea; Decreased compliance due to capillary leak, hypoxemia, increased

respiratory drive, increased secretions, and occasionally infection-related
bronchospasm all lead to dyspnea.

hypoxemic vasoconstriction The systemic circulation dilates in the presence of

hypoxia, in contrast to the pulmonary circulation, which vasoconstricts. This
response of the pulmonary circulation is known as hypoxic pulmonary
vasoconstriction and is a protective physiological reflex that aims to divert blood flow
away from hypoxic areas of the lungs to areas with better ventilation and oxygenation

PATHOLOGY
Classic pneumonia evolves through a series of pathologic changes, This
pattern has been described best for lobar pneumococcal pneumonia and may
not apply to pneumonia of all etiologies, especially viral or Pneumocystis
pneumonia.
Initial phase is one of edema with the presence of a proteinaceous exudate—
and often of bacteria—in the alveoli.
Red hepatization phase The presence of erythrocytes in the cellular intra-
alveolar exudate gives this second stage its name, but neutrophil influx is more
important with regard to host defense
Third phase, gray hepatization: no new erythrocytes are extravasating, and
those already present have been lysed and degraded. The neutrophil is the
predominant cell, fibrin deposition is abundant, and bacteria have
disappeared . This phase corresponds with successful containment of the
infection and improvement in gas exchange.
Final phase resolution: the macrophage reappears as the dominant cell type in
the alveolar space, and the debris of neutrophils, bacteria, and fibrin has been
cleared, as has the inflammatory response.

Pathology in other pneumonia’s

In VAP, respiratory bronchiolitis may precede the development of a
radiologically apparent infiltrate.
Because of the microaspiration mechanism, a bronchopneumonia pattern is
most common in nosocomial pneumonias, whereas a lobar pattern is more
common in bacterial CAP.
Despite the radiographic appearance, viral and Pneumocystis pneumonias
represent alveolar rather than interstitial processes.

COMMUNITY-ACQUIRED PNEUMONIA
list of potential etiologic agents in CAP includes bacteria, fungi, viruses, and
protozoa.
Newly identified pathogens include metapneumoviruses, the
coronaviruses responsible for severe acute respiratory syndrome (SARS) and
Middle East respiratory syndrome (MERS), and
community-acquired strains of MRSA.
Most cases of CAP, however, are caused by relatively few pathogens
Streptococcus pneumoniae is most common, other organisms must also be
considered in light of the patient’s risk factors and severity of illness
Typical bacterial pathogens:
Includes S. pneumoniae, Haemophilus influenzae, and (in selected patients)
S. aureus and gram-negative bacilli such as Klebsiella pneumoniae and
Pseudomonas aeruginosa.
Overall, with the increasing use of pneumococcal vaccine, the incidence of
pneumococcal pneumonia appears to be decreasing. M. pneumoniae and C.
pneumoniae, however, appear to be increasing in incidence, especially among
young adults
S. aureus pneumonia is well known to complicate influenza infection.
MRSA has been reported as a primary etiologic agent of CAP.
While this entity is still relatively uncommon, clinicians must be aware of its
potentially serious consequences, such as necrotizing pneumonia.

Atypical organisms:

Mycoplasma pneumoniae,
Chlamydia pneumoniae, and
Legionella species as well as
respiratory viruses
influenza viruses
adenoviruses
human metapneumovirus, and
Respiratory syncytial viruses. The most common of these viruses are
influenza, parainfluenza, and respiratory syncytial viruses

Atypical pathogens intrinsically resistant to all β-lactam agents and must be

treated with a macrolide fluoroquinolone, or a tetracycline.
~10–15% of CAP cases that are polymicrobial, the etiology usually includes a
combination of typical and atypical pathogens
Anaerobes
Anaerobes play a significant role only when an episode of aspiration has
occurred days to weeks before presentation for pneumonia
The combination of an unprotected airway (e.g., in patients with alcohol or
drug overdose or a seizure disorder) and significant gingivitis constitutes the
major risk factor.
Anaerobic pneumonias are often complicated by abscess formation and by
significant empyemas or parapneumonic effusions.

The risk factors for CAP

The risk factors for CAP in general and for pneumococcal pneumonia in
particular have implications for treatment regimens
Risk factors for CAP include alcoholism, asthma, immunosuppression,
institutionalization, and an age of ≥70 years
Risk factors for pneumococcal pneumonia include dementia, seizure
disorders, heart failure, cerebrovascular disease, alcoholism, tobacco
smoking, chronic obstructive pulmonary disease (COPD), and HIV infection.
CA-MRSA pneumonia is more likely in patients with skin colonization or
infection with CA-MRSA
Enterobacteriaceae tend to infect patients who have recently been
hospitalized and/or received antibiotic therapy or who have comorbidities
such as alcoholism, heart failure, or renal failure
P. aeruginosa is a particular problem in patients with severe structural lung
disease, such as bronchiectasis, cystic fibrosis, or severe COPD.

Risk factors for Legionella infection include diabetes, hematologic

malignancy, cancer, severe renal disease, HIV infection, smoking, male
gender, and a recent hotel stay or ship cruise.

CLINICAL MANIFESTATIONS:
The patient is frequently febrile with tachycardia or may have a history of
chills and/or sweats
Cough may be either non-productive or productive of mucoid, purulent, or
blood-tinged sputum.
Gross hemoptysis is suggestive of CA-MRSA pneumonia.
Depending on severity, the patient may be able to speak in full sentences or
may be very short of breath
If the pleura is involved, the patient may experience pleuritic chest pain.
Up to 20% of patients may have gastrointestinal symptoms such as nausea,
vomiting, and/or diarrohea
Other symptoms may include fatigue, headache, myalgias, and arthralgias.

Physical examination
Findings on physical examination vary with the degree of pulmonary
consolidation and the presence or absence of a significant pleural effusion.
An increased respiratory rate and use of accessory muscles of respiration are
common.
Palpation may reveal increased or decreased tactile fremitus, and the
percussion note can vary from
dull (reflecting underlying consolidated lung )
to
flat, (pleural fluid) respectively.
Auscultation : Crackles, bronchial breath sounds, and possibly a pleural
friction rub may be heard on auscultation.
Severely ill patients may have septic shock and evidence of organ failure.

Risk of cardiac complications

The risk of cardiac complications secondary to enhanced inflammation and
procoagulant activity is increased.
These complications include
myocardial infarction,
congestive heart failure, and arrhythmias, particularly in the elderly.

In Pneumococcal CAP, the increased risk of acute coronary events may be

partially driven by Pneumolysis (The loosening of any portion of lung
adherent to the chest wall) which increases platelet activation.
Up to 90% of acute coronary syndromes occur in the first week after onset of
CAP,
and the risk of new-onset congestive heart failure in elderly hospitalized CAP
patients can extend up to 1 year.

DIAGNOSIS
Infectious and non-infectious entities such as acute bronchitis, acute
exacerbations of chronic bronchitis, heart failure, pulmonary embolism,
hypersensitivity pneumonitis, and radiation pneumonitis.
The importance of a careful history cannot be overemphasized. For example,
known cardiac disease may suggest worsening pulmonary edema,
while underlying carcinoma may suggest lung injury secondary to irradiation.
58% and 67%, respectively the sensitivity and specificity of the findings on
physical examination. the elderly may initially present with confusion alone.

Radiographic findings
Radiographic findings may include risk factors for increased severity (e.g.,
cavitation or multi-lobar involvement)
radiographic results suggest an etiologic diagnosis.
Pneumatoceles suggest infection with S. aureus
upper-lobe cavitating lesion suggests tuberculosis.

CT
CT may be of value in a patient with suspected postobstructive pneumonia
caused by a tumor or foreign body or suspected cavitary disease.

Etiologic Diagnosis
The etiology of pneumonia usually cannot be determined solely on the basis of
clinical presentation.
Except for CAP patients admitted to the ICU, no data exist to show that
treatment directed at a specific pathogen is statistically superior to empirical
therapy.
benefit of establishing a microbial etiology
Identification of an unexpected pathogen allows narrowing of the initial
empirical regimen, thereby decreasing antibiotic selection pressure and
lessening the risk of resistance

GRAM’S STAIN AND CULTURE OF SPUTUM

Main purpose of the sputum Gram’s stain is to ensure that a sample is suitable
for culture.
Gram’s staining may also identify certain pathogens (e.g., S. pneumoniae, S.
aureus, and gram-negative bacteria) by their characteristic appearance.
To be adequate for culture, a sputum sample must have >25 neutrophils and
<10 squamous epithelial cells per low-power field.
positive cultures from sputum samples is ≤50%.
Even in cases of proven bacteremic pneumococcal pneumonia,
the greatest benefit of staining and culturing respiratory secretions is to alert
the physician of unsuspected and/or resistant pathogens and to permit
appropriate modification of therapy.

BLOOD CULTURES
Only 5–14% of cultures of blood from patients hospitalized with CAP are
positive, and the most frequently isolated pathogen is S. pneumoniae.
Certain high-risk patients—including those with neutropenia secondary to
pneumonia, asplenia, complement deficiencies, chronic liver disease, or
severe CAP— should have blood cultured.

URINARY ANTIGEN TESTS:

Two commercially available tests detect pneumococcal and Legionella antigen
in urine.
The test for Legionella pneumophila detects only serogroup 1, but this
serogroup accounts for most community-acquired cases of Legionnaires’
disease in the United States
sensitivity and specificity of the Legionella urine antigen test are as high as
70% and 99%, respectively.
The pneumococcal urine antigen test is also quite sensitive and specific (70%
and >90%, respectively)
Although false-positive results can be obtained with samples from
pneumococcus-colonized children, the test is generally reliable.

POLYMERASE CHAIN REACTION

PCR of nasopharyngeal swabs, for example, has become the standard for
diagnosis of respiratory viral infection.
PCR can detect the nucleic acid of Legionella species, M. pneumoniae, C.
pneumoniae, and mycobacteria.
In patients with pneumococcal pneumonia, an increased bacterial load
documented in whole blood by PCR is associated with an increased risk of
septic shock, the need for mechanical ventilation, and death
Clinical availability of such a test could conceivably help identify patients
suitable for ICU admission.

SEROLOGY
A fourfold rise in specific IgM antibody titer between acute- and convalescent-
phase serum samples is generally considered diagnostic of infection with the
pathogen in question.

BIOMARKERS
A number of substances can serve as markers of severe inflammation.
The two most commonly in use are
C-reactive protein (CRP) and procalcitonin (PCT).
Levels of these acute-phase reactants increase in the presence of an
inflammatory response, particularly to bacterial pathogens.
CRP may be of use in the identification of worsening disease or treatment
failure

Procalcitonin (PCT)
PCT may play a role in distinguishing bacterial from viral infection,
determining the need for antibacterial therapy, or deciding when to
discontinue treatment.
PCT testing can result in less antibiotic use in CAP with no concomitant
increase in treatment failure or mortality risk
These tests should not be used on their own, but, when interpreted in
conjunction with other findings from the history, physical examination,
radiology, and laboratory tests, may help with antibiotic stewardship and
appropriate management of seriously ill patients with CAP.

SITE OF CARE :
Septic shock or respiratory failure in the emergency department is an obvious
indication for ICU care.

Pneumonia Severity Index (PSI)

Points are given for 20 variables, including age, coexisting illness, and
abnormal physical and laboratory findings.
On the basis of the resulting score, patients are assigned to one of five classes
with the following mortality rates: class 1, 0.1%; class 2, 0.6%; class 3, 2.8%;
class 4, 8.2%; class 5, 29.2%.
clinical trials demonstrate that routine use of the PSI results in lower
admission rates for class 1 and class 2 patients.
Patients in class 3 could ideally be admitted to an observation unit until
further decision can be made.

CURB-65
criteria include five variables:
confusion (C);
urea >7 mmol/L (U);
respiratory rate ≥30/min (R);
blood pressure, systolic ≤90 mmHg or diastolic ≤60 mmHg (B); and
age ≥65 years.
Patients with a score of 0 =among whom the 30-day mortality rate is 1.5%, can
be treated outside the hospital.
With a score of 1 or 2, the patient should be hospitalized unless the score is
entirely or in part attributable to an age of ≥65 years.
In such cases, hospitalization may not be necessary.

Among patients with scores of ≥3, mortality rates are 22% overall; these
patients may require ICU admission
Neither PSI nor CURB-65 is accurate in determining the need for ICU
admission.

ANTIBIOTIC RESISTANCE
S. pneumoniae
For CAP, the main resistance issues currently involve S. pneumoniae and CA-
MRSA.
Pneumococcal resistance to penicillin with reduced susceptibility to other
drugs, such as macrolides, tetracyclines, trimethoprim-sulfamethoxazole,

The most important risk factor for antibiotic-resistant pneumococcal infection

is use of a specific antibiotic within the previous 3 months.
Risk factors for penicillin-resistant pneumococcal infection include
1)recent antimicrobial therapy,
2)an age of <2 years or >65 years,
3)attendance at day-care centers,
4)recent hospitalization, and
5) HIV infection.
Resistance to penicillin Pneumococcal resistance is acquired by direct DNA
incorporation and remodeling resulting from contact with closely related oral
commensal bacteria, by the process of natural transformation, or by mutation
of certain genes.
Resistance To rest of antibiotics Target-site modification caused by ribosomal
methylation in 23S rRNA encoded by the ermB gene results in high-level
resistance (MICs, ≥64 μg/mL) (minimum inhibitory concentration (MIC) is
the lowest concentration of a chemical, usually a drug, which prevents visible
growth of a bacterium or bacteria to macrolides, lincosamides, and
streptogramin B–type antibiotics. )
The efflux mechanism encoded by the mef gene (M phenotype) is usually
associated with low-level resistance (MICs, 1–32 μg/mL)
These two mechanisms account for ~45% and ~65%, respectively, of resistant
pneumococcal isolates in the United States
Pneumococcal resistance to fluoroquinolones (e.g., ciprofloxacin and
levofloxacin) changes can occur in one or both target sites (topoisomerases II
and IV) from mutations in the gyrA and parC genes, respectively. In
addition, an efflux pump may play a role in pneumococcal resistance to
fluoroquinolones

CA-MRSA
Methicillin resistance in S. aureus is determined by the mecA gene, which
encodes for resistance to all β-lactam drugs
CA-MRSA isolates tend to be less resistant than the older hospital acquired
strains and are often susceptible to trimethoprim-sulfamethoxazole,
clindamycin, and tetracycline in addition to vancomycin and linezolid.
most important distinction is that CA-MRSA strains also carry genes for
superantigens, such as
enterotoxins B and C and
Panton-Valentine leukocidin,
membrane-tropic toxin that can create cytolytic pores in polymorphonuclear
neutrophils, monocytes, and macrophages.

Gram-Negative Bacilli resistance

Enterobacter species are typically resistant to cephalosporins; the drugs of
choice for use against these bacteria are fluoroquinolones or carbapenems.
when infections due to bacteria producing extendedspectrum β-lactamases are
documented or suspected, a fluoroquinolone or a carbapenem should be
used. E.coli resistant to fluoroquinolones

INITIAL ANTIBIOTIC MANAGEMENT

initial therapy is usually empirical, designed to cover the most likely pathogens
Empirical treatment regimens for CAP are listed in Table 121-5. In general,
the recommendations in the IDSA/ATS guidelines published in 2007
continue to apply but with a possible exception for treatment of outpatients
who have previously been well and have not received an antibiotic within 3
months.Fluoroquinolone or a β-lactam plus a macrolide should be used.
Doxycycline as mono therapy can be used if suspected macro like resistance in
outpatient.
A meta-analysis found ceftaroline to be superior to ceftriaxone as the β-
lactam component of IV empirical treatment of CAP in hospitalized patients in
PORT/PSI risk class III or IV who have not received prior antibiotics.

Once the etiologic agent(s) and their susceptibilities are known, therapy may
be altered to target the specific pathogen(s).

If CA-MRSA is suspected, either linezolid or vancomycin—with or without

clindamycin to inhibit toxin production—can be added to the initial empirical
regimen
some drugs—particularly the fluoroquinolones—are very well absorbed and
can be given orally from the outset to certain patients. For patients initially
treated IV, a switch to oral treatment is appropriate as long as the patient can
ingest and absorb the drugs, is hemodynamically stable, and is showing
clinical improvement.

ADJUNCTIVE MEASURES
Adequate hydration, oxygen therapy for hypoxemia, vasopressors, and
assisted ventilation when necessary are critical to successful treatment
Randomized placebo-controlled trials have shown a benefit in treatment of
hospitalized patients and patients who have severe CAP with prednisone and
methylprednisolone, respectively.
FAILURE TO IMPROVE:
Patients slow to respond to therapy should be re-evaluated at about day 3
(sooner if their condition is worsening rather than simply not improving), and
several possible scenarios should be considered. A number of non-infectious
conditions mimic pneumonia, including
1. pulmonary edema,
2. pulmonary embolism,
3. lung carcinoma,
4. radiation and hypersensitivity pneumonitis, and
5. connective tissue disease involving the lungs
lack of response may be because pathogen is resistant to the drug selected, or a
sequestered focus (e.g., lung abscess or empyema) may be blocking access of
the antibiotic(s) to the pathogen.
The patient may be getting either the wrong drug or the correct drug at the
wrong dose or frequency of administration.
CAP is the correct diagnosis but an unsuspected pathogen (e.g., CA-MRSA, M.
tuberculosis, or a fungus) is the cause.
Nosocomial superinfections—both pulmonary and extrapulmonary— are
other possible explanations for a hospitalized patient’s failure to improve or
deterioration.
COMPLIC
ATIONS:
Complications of severe CAP include respiratory failure, shock and
multiorgan failure, coagulopathy, and exacerbation of comorbid illnesses.
Three particularly noteworthy conditions are metastatic infection lung
abscess, and complicated pleural effusion.
Rare conditions Metastatic infection (e.g., brain abscess or endocarditis)
Lung abscess may occur in association with aspiration or with infection caused
by a single CAP pathogen, such as CA-MRSA, P. aeruginosa, or (rarely) S.
pneumoniae.

A significant pleural effusion should be tapped for both diagnostic and

therapeutic purposes
If the
fluid has a
pH of <7, a
glucose level of <2.2 mmol/L,
lactate dehydrogenase concentration of >1000 U/L
or
if bacteria are seen or cultured, it should be completely drained;
a chest tube is often required, and video-assisted thoracoscopy may be
needed for late treatment or difficult cases.

FOLLOW-UP:
Fever and leukocytosis usually resolve within 2–4 days in otherwise healthy
patients with CAP,physical findings may persist longer.
Chest radiographic abnormalities are slowest to resolve (4–12 weeks
with the speed of clearance depending on the patient’s age and underlying
lung disease.
For a hospitalized patient, a follow-up radiograph ~4–6 weeks later is
recommended.

PROGNOSIS:
The prognosis of CAP depends on the patient’s age, comorbidities, and site
of treatment (inpatient or outpatient). Young patients without comorbidity
do well and usually recover fully after ~2 weeks
The overall mortality rate for the outpatient group is <5%.

PREVENTION
The main preventive measure is vaccination
A pneumococcal polysaccharide vaccine (PPSV23) contains capsular material
from 23 pneumococcal serotypes;
a protein conjugate pneumococcal vaccine (PCV13) are available in the United
States capsular polysaccharide from 13 of the most common pneumococcal
pathogens affecting children is linked to an immunogenic protein, PCV13
produces T cell–dependent antigens that result in long-term immunologic
memory.
In the event of an influenza outbreak, unprotected patients at risk from
complications should be vaccinated immediately and given
chemoprophylaxis with either 1)oseltamivir or 2)zanamivir for 2 weeks— i.e.,
until vaccine-induced antibody levels are sufficiently high.

VENTILATOR-ASSOCIATED PNEUMONIA
Most research on hospital-acquired pneumonia has focused on VAP.
The greatest difference between VAP and HAP studies is the dependence on
expectorated sputum for a microbiologic diagnosis of HAP (as for that of
CAP), which is further complicated by frequent colonization by pathogens in
patients with HAP.
VAP diagnosed by lower respiratory specimen ET aspiration

ETIOLOGY
The non-MDR group is nearly identical to the pathogens found in severe CAP
if patients have other risk factors, MDR pathogens are a consideration, even
early in the hospital course.

EPIDEMIOLOGY:
Highest hazard ratio in the first 5 days and a plateau in additional cases (1%
per day) after ~2 weeks.
the cumulative rate among patients who remain ventilated for as long as 30
days is as high as 70%.
Three factors are critical in the pathogenesis of VAP
1)colonization of the oropharynx with pathogenic microorganisms,
2)aspiration of these organisms from the oropharynx into the lower
respiratory tract, and
3)compromise of the normal host defense mechanisms.

Risk factors and their corresponding prevention strategies pertain to one of these
three factors
 In a high percentage of critically ill patients, the normal oropharyngeal flora is
replaced by pathogenic microorganisms.
The most important risk factors are
1)antibiotic selection pressure,
2)cross-infection from other infected/colonized
3)patients or contaminated equipment, and malnutrition.
Of these factors, antibiotic exposure poses the greatest risk by far.
Pathogens such as P. aeruginosa almost never cause infection in patients
without prior exposure to antibiotics.
Hyperglycemia and more frequent transfusions adversely affect the immune
response.
Almost all intubated patients experience microaspiration and are at least
transiently colonized with pathogenic bacteria.

CLINICAL MANIFESTATIONS
in VAP as in all other forms of pneumonia: fever, leukocytosis, increase in
respiratory secretions, and pulmonary consolidation on physical
examination, along with a new or changing radiographic infiltrate.
Other clinical features may include tachypnea, tachycardia, worsening
oxygenation, and increased minute ventilation.

DIAGNOSIS
No single set of criteria is reliably diagnostic of pneumonia in a ventilated
patient.
Differential diagnosis of VAP includes a number of entities such as
1)atypical pulmonary edema,
2)pulmonary contusion,
3)alveolar hemorrhage,
4)hypersensitivity pneumonitis,
5)acute respiratory distress syndrome, and
6)pulmonary embolism.
Clinical findings in ventilated patients with fever and/or leukocytosis may
have alternative causes, including antibiotic-associated diarrhea, central
line–associated infection, sinusitis, urinary tract infection, pancreatitis, and
drug fever.

2. Quantitative-Culture Approach >>

The essence of the quantitative-culture approach is discrimination between
colonization and true infection through determination of the bacterial burden.
The key piece of a quantitative-culture approach is to base subsequent
antibiotic therapy on the results of the quantitative cultures.
expertise in quantitative-culture techniques is critical, with a specimen
obtained as soon as pneumonia is suspected and before antibiotic therapy is
initiated or changed
The more distal in the respiratory tree the diagnostic sampling, the more
 specific the results and therefore the lower the threshold of growth necessary
to diagnose pneumonia and exclude colonization.

3. Clinical Approach >>

General knowledge of the lack of specificity of a clinical diagnosis of VAP and
results from invasive quantitativeculture studies have actually improved the
clinical approach to the diagnosis of VAP.

4. TREATMENT Ventilator-Associated Pneumonia >>

The key to appropriate antibiotic management of VAP is an appreciation of

the resistance patterns of the most likely pathogens in a given patient
The major factor in the selection of agents is the presence of risk factors for
MDR pathogens.
Choices among the various options listed depend on 1)local patterns of
resistance 2)very important factor—the patient’s prior antibiotic exposure.
3)Knowledge of the local hospital’s— and even the specific ICU’s—
antibiogram and the local incidence of specific MDR pathogens (e.g., MRSA) is
critical in selecting appropriate empirical therapy.

The major difference from CAP is the markedly lower incidence of atypical
pathogens in VAP; the exception is Legionella, which can be a nosocomial
pathogen, especially with breakdowns in the treatment of potable water in the
hospital.

5. ANTIBIOTIC RESISTANCE >>

If not for the higher risk of infection with MDR pathogens (Table 121-6), VAP
could be treated with the same antibiotics used for severe CAP.
Frequent use of β-lactam drugs, especially cephalosporins, appears to be the
major risk factor for infection with MRSA and extended-spectrum β-
lactamase–positive strains.
P. aeruginosa has demonstrated the ability to develop resistance to all
routinely used antibiotics
Acinetobacter species, Stenotrophomonas maltophilia, and Burkholderia
cepacia are intrinsically resistant to many of the empirical antibiotic regimens
employed
VAP caused by these pathogens emerges during treatment of other infections,
and resistance is always evident at initial diagnosis.
6. 8 Empirical Antibiotic Treatment of Hospital-Acquired and Ventilator-Associated
Pneumonia >>

7. Standard recommendation for patients with risk factors for MDR infection >>
standard recommendation for patients with risk factors for MDR infection is
for three antibiotics: two directed at P. aeruginosa and one at MRSA.
A β-lactam agent provides the greatest coverage, yet even the broadest-
spectrum agent—a carbapenem—still provides inappropriate initial therapy in
up to 10–15% of cases at some centers.
The emergence of carbapenem resistance at some institutions requires the
addition of polymyxins to the combination-therapy options.

8. SPECIFIC TREATMENT >>

Once an etiologic diagnosis is made, broad-spectrum empirical therapy can be
modified to specifically address the known pathogen
 A negative tracheal-aspirate culture or growth below the threshold for
quantitative cultures of samples obtained before any antibiotic change
strongly suggests that antibiotics should be discontinued or that a search for
an alternative diagnosis should be pursued.
The major controversy regarding specific therapy for VAP concerns the need
for ongoing combination treatment of Pseudomonas pneumonia. No
randomized controlled trials have demonstrated a benefit of combination
therapy with a β-lactam and an aminoglycoside, nor have subgroup analyses in
other trials found a survival benefit with such a regimen.

9. FAILURE TO IMPROVE >>

FAILURE TO IMPROVE
Treatment failure is not uncommon in VAP, especially that caused by MDR
pathogens.
. VAP caused by MRSA is associated with a 40% clinical failure rate when
treated with standard-dose vancomycin.
Linezolid appears to be 15% more efficacious than even adjusted-dose
vancomycin and is clearly preferred in patients with renal insufficiency and
those infected with high-MIC isolates of MRSA.
. VAP due to Pseudomonas has a 40–50% failure rate, no matter what the
regimen.
Recurrent VAP caused by the same pathogen is possible because the biofilm
on endotracheal tubes allows reintroduction of the microorganism
Studies of VAP caused by Pseudomonas show that approximately half of
recurrent cases are caused by a new strain.

10. differential diagnosis of treatment failure >>

1)Pneumonia due to a new superinfection 2)presence of extrapulmonary
infection 3)drug toxicity must be considered in the differential diagnosis of
treatment failure.
Serial measurements of procalcitonin levels appear to track the clinical
response accurately, while repeat quantitative cultures may clarify the
microbiologic response.

11. COMPLICATIONS of VAP >>

Apart from death, the major complication of VAP is prolongation of
mechanical ventilation, with corresponding increases in the duration of ICU
stay and hospitalization.
, an additional week of mechanical ventilation resulting from VAP is common
rare cases
, necrotizing pneumonia (e.g., that due to P. aeruginosa) can cause significant
pulmonary hemorrhage.

12. long-term complications >>

necrotizing infections result in the long-term complications of bronchiectasis
and parenchymal scarring leading to recurrent pneumonia
13. Clinical improvement >>
Clinical improvement, if it occurs, is usually evident within 48–72 h of the
initiation of antimicrobial treatment.
findings on chest radiography often worsen initially during treatment, they are
less helpful than clinical criteria as an indicator of clinical response in severe
pneumonia.

14. PROGNOSIS >>

mortality rates as high as 50–70%,
Many patients with VAP have underlying diseases that would result in death
even if VAP did not occur.
Attributable mortality exceeded 25%
MDR pathogens are associated with significantly greater attributable mortality
than non-MDR pathogens
Pneumonia caused by some pathogens (e.g., S. maltophilia) is simply a marker
for a patient whose immune system is so compromised that death is almost
inevitable.

15. PREVENTION >>

1)most important preventive intervention is to avoid intubation or minimize
its duration
2)Successful noninvasive ventilation avoids many of the problems associated
with endotracheal tubes.
3)Strategies that minimize the duration of ventilation through daily holding of
sedation and formal weaning protocols have also been highly effective in
preventing VAP. 4)Short-course antibiotic prophylaxis can decrease the risk
of VAP in comatose patients requiring intubation, and data suggest that
antibiotics decrease VAP rates overall. the major benefit appears to be a
decrease in the incidence of early-onset VAP, which is usually caused by the
less pathogenic non-MDR microorganisms. 5)Minimizing microaspiration
around the endotracheal tube cuff is also a strategy for avoidance of VAP.
Simply elevating the head of the bed (at least 30° above horizontal but
preferably 45°) decreases VAP rates. 6) The risk-to-benefit ratio of
transporting the patient outside the ICU for diagnostic tests or procedures
should be carefully considered, since VAP rates are increased among
transported patients. 7) emphasis on controlling overgrowth of the bowel flora
by avoidance of agents that raise gastric pH may be relevant only in certain
populations, such as liver transplant recipients and patients who have
undergone other major intraabdominal procedures or who have bowel
obstruction. 8) Education and reminders of the need for consistent hand
washing and other infection-control practices can minimize this risk.
16. Other important points >>
VAP caused by Pseudomonas is rare among patients who have not recently
received antibiotics. Heavy continuous sedation increases VAP risk, but self-
extubation because of insufficient sedation is also a risk. prolonged courses of
antibiotics consistently increase the risk of VAP caused by more lethal MDR
pathogens. MRSA and the nonfermenters P. aeruginosa and Acinetobacter
species are not normally part of the bowel flora but reside primarily in the
nose and on the skin, respectively.

17. HOSPITAL-ACQUIRED PNEUMONIA >>

HAP in non-intubated patients—both inside and outside the ICU—is similar to
VAP.
The main differences are the higher frequency of non-MDR pathogens and the
generally better underlying host immunity in non-intubated patients.
The lower frequency of MDR pathogens allows monotherapy in a larger
proportion of cases of HAP than of VAP.
The only pathogens that may be more common in the non-VAP population are
anaerobes
The greater risk of macroaspiration by non-intubated patients and the lower
oxygen tensions in the lower respiratory tract of these patients increase the
likelihood of a role for anaerobes.
As in the management of CAP, specific therapy targeting anaerobes probably is
not needed since many of the recommended antibiotics are active against
anaerobes.
blood cultures are infrequently positive (<15% of cases)
Diagnosis is even more difficult
Lower respiratory tract samples appropriate for culture are considerably more
difficult to obtain
Many of the underlying diseases that predispose a patient to HAP are also
associated with an inability to cough adequately
the better host defenses in non-ICU patients result in lower mortality rates
than are documented for VAP. In addition, the risk of antibiotic failure is
lower in HAP.