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528 PART 4: Pulmonary Disorders
Values within 1 log10 of the cutoff must, however, be interpreted cau- contradict those findings, as some patients had sterile cultures of PSB
tiously, and bronchoscopy should be repeated in symptomatic patients specimens from the noninvolved lung. 32,214 Furthermore, although the
with a negative (<10 cfu/mL) result. Many technical factors, includ- authors of most studies concluded that the sensitivities of nonbron-
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4
ing medium and adequacy of incubation, and antibiotic or other toxic choscopic and bronchoscopic techniques were comparable, the overall
components, may influence results. Reproducibility of PSB sampling has concordance was only approximately 80%, emphasizing that, in some
been recently evaluated by three groups. 206-208 Although in vitro repeat- patients, the diagnosis could be missed by a blind technique, especially
ability was excellent and in vivo qualitative recovery 100%, quantitative in the case of pneumonia involving the left lung. 32
results were more variable. In 14% to 17% of patients, results of replicate ■
samples fell on both sides of the 10 cfu/mL threshold, and results varied PATIENTS ALREADY RECEIVING ANTIMICROBIAL THERAPY
3
by more than 1 log10 in 59% to 67% of samples. 206-208 This variability is Performing microbiologic cultures of pulmonary secretions for diag-
presumably related to both the irregular distribution of organisms in nostic purposes after initiation of new antibiotic therapy in patients
secretions and the very small volume actually sampled by PSB. As with suspected of having developed VAP leads to a high rate of false-negative
all diagnostic tests, borderline PSB and/or BAL quantitative culture results, regardless of the method of obtaining the secretions. In fact,
results should be interpreted cautiously, and the clinical circumstances all microbiological techniques are of limited value in patients with a
should be considered before reaching any therapeutic decision. recent infiltrate who have received new antibiotics, even for less than
The most compelling argument for invasive techniques coupled with 24 hours. A negative finding could indicate that the patient has been
quantitative cultures of PSB or BAL specimens is that they can reduce successfully treated for pneumonia and the bacteria are eradicated, or
excessive antibiotic use. There is little disagreement that the clinical that the patient had no lung infection to begin with. Using both PSB and
diagnosis of nosocomial pneumonia is overly sensitive and leads to the BAL, Souweine et al prospectively investigated 63 episodes of suspected
unnecessary use of broad-spectrum antibiotics. Because bronchoscopic VAP. If patients had been treated with antibiotics but did not have
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techniques may be more specific, their use would reduce antibiotic a recent change in antibiotic class, sensitivity of PSB and BAL culture
pressure in the ICU, thereby limiting the emergence of drug-resistant (83% and 77%, respectively) were similar to the sensitivities achieved in
strains and the attendant increased risks of superinfection. 36,209 When patients not being treated with antibiotics. In other words, prior therapy
culture results are available, BAL and/or PSB techniques facilitate precise did not reduce the yield of diagnostic testing among patients receiving
identification of the offending organisms and their susceptibility pat- current antibiotics given to treat a prior infection. Conversely, if therapy
terns. Such data are invaluable for optimal antibiotic selection in patients was recent, sensitivity of invasive diagnostic methods, using traditional
with a true VAP. They also increase the confidence and comfort level of thresholds, was only 38% with BAL and 40% with PSB. These two
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health care workers in managing patients with suspected nosocomial clinical situations should be clearly distinguished before interpreting
pneumonia. The more targeted use of antibiotics also could reduce the results of pulmonary secretion cultures, irrespective of how they
210
overall costs, despite the expense of bronchoscopy and quantitative cul- were obtained. In the second situation, when the patient receives new
tures, and minimize antibiotic-related toxicity. This is particularly true antibiotics after the appearance of signs suggesting VAP, no conclusion
in patients who have late-onset VAP, in whom expensive combination concerning the presence or absence of pneumonia can be drawn if cul-
therapy is commonly recommended. A conservative cost-analysis in a ture results are negative. 215-217 Pulmonary secretions therefore need to
trauma ICU suggested that the discontinuation of antibiotics upon the be obtained before starting new antibiotics, as is the case for all types of
return of negative bronchoscopic quantitative culture results could lead microbiologic samples.
to a savings of more than $1700 per patient suspected of VAP. 211
Finally, a major benefit of a negative bronchoscopy is to direct atten- ■ USE OF PROCALCITONIN AND OTHER BIOLOGICAL MARKERS
tion away from the lungs as the source of fever. Many hospitalized Procalcitonin (PCT), a 116-amino-acid peptide which is one of the
patients with negative bronchoscopic cultures have other potential sites precursors of the hormone calcitonin, has been described as a good
of infection that can be identified via a simple diagnostic protocol. In diagnostic marker of bacterial infection in patients with community-
50 patients with suspected VAP who underwent a systematic diagnostic acquired infections, especially in patients with lower respiratory tract
protocol designed to identify all potential causes of fever and pulmonary infection. 218-221 Moreover, several interventional trials have shown that
densities, Meduri et al confirmed that lung infection was present in only PCT could be used to start or to postpone antibiotic treatment in com-
42% of cases; the frequent occurrence of multiple infectious and nonin- munity-acquired lower respiratory tract infections. 222-226 In patients with
fectious processes justifies a systematic search for the source of fever in nosocomial infections, and in particular in patients with VAP, its use-
this setting. Delay in diagnosis or definitive treatment of the true site fulness as a diagnostic marker is more doubtful. 227-231 There are several
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of infection may lead to prolonged antibiotic therapy, more antibiotic- reasons to explain why PCT is not a good diagnostic marker in patients
associated complications, and induction of further organ dysfunction. 212 with suspected VAP. First, pneumonia may be a localized infection; thus,
■ QUANTITATIVE CULTURES OF DISTAL SPECIMENS as for other localized infections, PCT can be synthesized locally without
OBTAINED WITHOUT BRONCHOSCOPY systemic release, explaining its low serum level or apparent decrease
in patients with true pulmonary infections. Second, ICU-patients may
At least 15 studies have described a variety of nonbronchoscopic tech- suffer from previous severe sepsis or septic shock, multiorgan failure, or
niques using various types of endobronchial catheters for sampling may have developed a systemic inflammatory response syndrome after
distal lower respiratory tract secretions; globally, results have been simi- surgery or trauma, conditions known to increase blood level of biomark-
lar to those obtained with bronchoscopy. Compared to conventional ers including PCT in the absence of infection. Thus, a high level of
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PSB and/or BAL, nonbronchoscopic techniques are less invasive, can be PCT the day VAP is suspected is not useful, because it is not possible to
performed by clinicians not qualified to perform bronchoscopy, have distinguish an elevation due to a previous noninfectious condition from
lower initial costs than bronchoscopy, avoid potential contamination by an elevation due to an active infection. Third, it is known that a time lag
the bronchoscopic channel, are associated with less compromise of gas- of 24 to 48 hours can exist between bacterial infection onset and peak
exchange during the procedure, and can be performed even in patients PCT release, and that may also explain the apparent low level of PCT on
intubated with small endotracheal tubes. Disadvantages include the the day of VAP onset. Incorporating PCT values in clinical score (such
potential sampling errors inherent in a blind technique and the lack of as CPIS) did not improve its diagnostic value. 229,230
airway visualization. Although autopsy studies indicate that pneumonia The soluble Triggering Receptor Expressed on Myeloid Cells-1
in ventilator-dependent patients has often spread into every pulmonary (sTREM-1) molecule is known to be specifically released during several
lobe and predominantly involves the posterior portion of the lower infectious processes. Although it was apparently a reliable marker of
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lobes, several clinical studies on ventilated patients with pneumonia pneumonia, especially VAP, more recent studies obtained contradictory
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