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CHAPTER 59: Ventilator-Associated Pneumonia 529

findings, thereby raising doubt as to its usefulness for VAP diagnosis. 228,233-235 remains controversial. 243,244 Yet, being able to withhold antimicrobial
Pending additional studies, and because this marker is not routinely treatment from some patients without infection may constitute a distinct
available, sTREM-1 is not recommended as an indicator to guide antibi- advantage in the long term: it minimizes the emergence of resistant
otic use in such situations. microorganisms in the ICU and redirects the search for another (the
GNB cause >80% of VAP episodes and are associated with high mor- true) infection site. 248,249
tality. Because GNB pneumonia might be diagnosed more rapidly by In patients with clinical evidence of severe sepsis and rapid worsen-
endotoxin measurement in BAL fluid, several investigators tested this ing organ dysfunction, hypoperfusion or hypotension, or patients with
hypothesis. 236-239 Applying a threshold of >5 EU/mL in BAL fluid yielded a very high pretest probability of disease, the initiation of antibiotic
the best operating characteristics for GNB-pneumonia diagnosis (100% therapy should not be delayed while awaiting bronchoscopy. Patients
sensitivity; 75% specificity; area under the ROC curve: 0.88) in a series should be given immediate antibiotics. In this situation, simple non-
of 63 hospitalized adults suspected of having lung infection. Three bronchoscopic procedures find their best justification, allowing distal
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other studies confirmed the potential contribution of this tool. 236,238,239 pulmonary secretions to be obtained on a 24-hour basis, just before
These findings suggest that endotoxin determination in BAL fluid might starting new antimicrobial therapy.
become an acceptable adjunct for the rapid diagnosis of GNB pneumo- Despite broad experience with PSB and BAL, it remains unclear
nia in a near future, when it will be available at the bedside. which should be used. Most investigators prefer BAL over PSB to
■ SUMMARY OF THE EVIDENCE diagnose bacterial pneumonia, because BAL: (1) has a slightly higher
sensitivity to identify VAP-causative microorganisms; (2) enables better
Aside from decision-analysis studies 240,241 and a single retrospective selection of an empiric antimicrobial treatment before culture results are
study, five trials have used a randomized scheme to assess the effect of available, based on microscopically examined cytocentrifuged prepara-
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a diagnostic strategy on antibiotic use and outcome in patients suspected tions; (3) is less dangerous for many critically ill patients; (4) is less
of having VAP 39,40,242-244 In three randomized studies conducted in Spain, costly; and (5) may provide useful clues for the diagnosis of other types
no differences in mortality and morbidity were found when either inva- of infections. Nevertheless, a very small return on BAL may contain
sive (PSB and/or BAL) or noninvasive (quantitative endotracheal aspi- only diluted material from the bronchial rather than alveolar level, and
rate cultures) techniques were used to diagnose VAP. 39,40,242 These studies thus give rise to false-negative results, particularly in patients with very
were relatively small, ranging from 51 to 88 patients. Antibiotics were severe COPD. In these patients, the value of BAL is greatly diminished
continued in all patients despite negative cultures, thereby offsetting the and PSB is preferred. 192
potential advantage of the specific diagnostic test in patients with sus- When bronchoscopy is not available, we recommend replacing
pected VAP. Several prospective studies have concluded that antibiotics bronchoscopy in the algorithm in Figure 59-2 by one of the simplified
can be stopped in patients with negative quantitative cultures, without nonbronchoscopic diagnostic techniques, or following the strategy
250
adversely affecting the recurrence of pneumonia and mortality. 196,245,246 described by Singh et al. Such an approach avoids prolonged treatment
In a French study in which 413 patients were randomized, those of patients with a low likelihood of infection, while allowing immediate
receiving bacteriological management using BAL and/or PSB had a treatment of patients with VAP.
lower mortality rate on day 14, lower sepsis-related organ failure assess-
ment scores on day 3 and 7, and less antibiotic use. Pertinently, 22 TREATMENT
243
egy group and only 5 in the clinical strategy group, suggesting that ■ EVALUATION OF CURRENT ANTIMICROBIAL STRATEGIES
nonpulmonary infections were diagnosed in the bacteriological strat-
overdiagnosis of VAP can lead to errors in identifying nonpulmonary Despite many advances in antimicrobial therapy, successful treatment
infections. A randomized trial conducted by the Canadian Critical Care of patients with nosocomial pneumonia remains a difficult and com-
Trials Group investigated the effect of different diagnostic approaches plex undertaking. No consensus has been reached concerning issues
on outcomes of 740 patients suspected of having VAP. There was no as basic as the optimal antimicrobial regimen for therapy or duration
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difference in the 28-day mortality rate in patients in whom BAL was of treatment. Although some investigators have recommended two-
used versus those in whom endotracheal-aspiration was used as the drug parenteral therapy for most cases, recent data have demonstrated
diagnostic strategy. The BAL group and the endotracheal-aspiration the efficacy of newer β-lactam antibiotics as monotherapy for some
group also had similar rates of targeted antibiotic therapy on day 6, patients. Similarly, the efficacy of endotracheal or aerosolized antibiotics
days alive without antibiotics, and maximum organ-dysfunction scores. as either the sole or adjunctive therapy for gram-negative pneumonia
Unfortunately, information about how the decision algorithms were remains controversial. In fact, to date, evaluation of various antimicro-
followed in the two diagnostic arms once cultures were available was bial strategies for the treatment of bacterial pneumonia in mechanically
not provided, raising uncertainties about how deescalation of antibiotic ventilated patients has been difficult for several reasons.
therapy was pursued in patients with negative BAL cultures. Obviously, First, as indicated earlier, obtaining a definitive diagnosis of pneu-
the potential benefit of using a diagnostic tool such as BAL for safely monia in critically ill patients is far from easy. Although clinically dis-
restricting unnecessary antimicrobial therapy in such a setting can only tinguishing between bacterial colonization of the tracheobronchial tree
be obtained when decisions regarding antibiotics are closely linked to and true nosocomial pneumonia is difficult, nearly all previous thera-
bacteriological results, including both direct examination and cultures peutic investigations have relied solely on clinical diagnostic criteria and
of respiratory specimens. therefore probably have included patients who did not have pneumonia.
■ CONCLUSIONS AND RECOMMENDATIONS Second, most of these studies used cultures of tracheal secretions as the
major source of samples for microbiologic analysis despite the fact that
Our personal bias is that use of bronchoscopic techniques to obtain the upper respiratory tract of most ventilated patients usually is colo-
BAL specimens from an affected area of the lung in ventilated patients nized with multiple potential pathogens. Finally, the lack of an adequate
with signs suggestive of pneumonia enables the formulation of a thera- technique to directly sample the infection site in the lung has hampered
peutic strategy superior to that based exclusively on clinical evaluation. study of both the ability or inability of antibiotics to eradicate the caus-
Bronchoscopic techniques, when performed before the introduction of ative pathogens from the lower respiratory tract and therefore the ability
new antibiotics, enable physicians to identify most patients who need to predict their bacteriologic efficacy.
immediate treatment, and help select optimal therapy in a safe and Montravers and colleagues evaluated the bacteriologic and clinical
well-tolerated manner. These techniques also avoid resorting to broad- efficacy of antimicrobial therapies selected on the basis of the etiologic
spectrum coverage of all patients who develop a clinical suspicion of microorganisms identified by cultures of PSB samples obtained during
infection. The full impact of this decision tree on patient outcome bronchoscopy for the treatment of nosocomial bacterial pneumonia in
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