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530 PART 4: Pulmonary Disorders

76 patients receiving MV. Using follow-up PSB sample culture to assess be easily increased through adaptation of a decision tree, and when the
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the infection site in the lung directly, their results demonstrated that the resources for the microbiological work-up are available. 259
two effective agents was able to sterilize or contain the lower respiratory ■ STOPPING THERAPY WHEN THE DIAGNOSIS
administration of an antimicrobial therapy combining, in most cases,
tract infection after only 3 days of treatment in 67 (88%) of the patients OF INFECTION BECOMES UNLIKELY
included in the study. The only two bacteriologic failures were observed Because clinical signs of infection are nonspecific and can be caused by
in patients who did not receive adequate treatment because of errors any condition associated with an inflammatory response, many more
in the selection of antimicrobial drugs. Early superinfection caused by patients than necessary are initially treated with antibiotics. Thus, it is
bacteria resistant to the initial antibiotics was, however, documented in important to use serial clinical evaluations and microbiologic data to
7 (9%) patients, emphasizing the need to monitor carefully the impact of reevaluate therapy after 48 to 72 hours. 1,263
treatment on the initial microbial flora for optimal management of such The decision tree should contain an explicit statement that patients
patients when the clinical response is suboptimal. Furthermore, results with a low probability of infection will be identified and therapy stopped
of cultures of follow-up PSB samples were well correlated with the clini- when infection appears unlikely. The algorithm cannot be exactly the
cal outcome noted during the 15-day observation period, making this same for a “clinical” or an “invasive” strategy, depending on the general
test a good prognostic indicator in patients with nosocomial bacterial principles and microbiological techniques on which the diagnostic strat-
pneumonia. Whereas the percentage of patients with clinical improve- egy is constructed (see section above on “Diagnosis”). Using a “clinical
ment was 96% and 82% in those with sterilized or persistent low-grade strategy” in which all patients with clinically suspected pulmonary
infection, respectively, it was only 44% in those with persistent high- infection are treated with new antibiotics, even when the likelihood
grade infection. Using such techniques to sample the infection site in of infection is low, the decision whether to continue antibiotics or not
the lung directly therefore may provide a more rigorous evaluation of on day 3 will be based essentially on a combination of clinical signs.
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different antimicrobial strategies. Briefly, antibiotics are discontinued if and only if the clinical diagnosis
■ INITIAL THERAPY of VAP is unlikely (there are no definite infiltrates found on chest radi-
ography at follow-up), tracheobronchial aspirate culture results are non-
Failure to initiate prompt appropriate and adequate therapy (the etiologic significant, and there is no severe sepsis or shock.
organism is sensitive to the therapeutic agent, the dose is optimal, and The decision algorithm for withholding or withdrawing antibiotics
the correct route of administration is used) has been a consistent factor using the “invasive strategy” is based on results of direct examination
associated with increased mortality. 44,164-166 Because pathogens associated of distal pulmonary samples obtained by bronchoscopic or nonbron-
with inappropriate initial empiric antimicrobial therapy mostly include choscopic BAL and results of quantitative cultures (Fig. 59-2). Briefly,
antibiotic-resistant microorganisms, such as P. aeruginosa, Acinetobacter antibiotics are withheld in patients with no bacteria on Gram-stained
species, K pneumoniae, Enterobacter species, and MRSA, patients at risk cytocentrifuged preparations and no signs of severe sepsis or septic
for infection with these organisms should initially receive a combination shock; and discontinued when quantitative culture results are below
of agents that can provide a very broad spectrum of coverage. 1,182 Several the cutoff defining a positive result, except in patients with proven
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observational studies have now confirmed that the use of a regimen that extrapulmonary infection and/or severe sepsis. As demonstrated by
combines initially a broad spectrum betalactam with an aminoglycoside several studies, patients managed with such a bacteriological strategy
increases the proportion of patients appropriately treated as compared receive fewer antibiotics, and more patients have all their antibiotics
to monotherapy or to a regimen combining a betalactam with a fluo- discontinued compared to the clinical strategy group, thereby confirm-
roquinolone. 171,251-253 Only patients with early-onset infection, mild or ing that the two strategies actually differed. 201,210,243,245,247 Future stud-
moderate disease severity, and no specific risk factors for multiresistant ies should, however, compare bronchoscopy against and in addition
strains, such as prolonged duration of hospitalization (>5 days), admis- to a clinical strategy incorporating an explicit statement for stopping
sion from a health care–related facility, recent prolonged antibiotic antibiotics in patients with a low probability of infection, for example,
therapy, and specific local epidemiological data, can be treated with a using the algorithm described above or the CPIS score, as proposed by
narrow-spectrum drug, such as a nonpseudomonal third-generation Singh et al. 155,185,250,264 Formal economic analysis is also required because
cephalosporin. 1,3,254 prevention of resistance and better antibiotic control may result in cost
When risk factors for multiresistant pathogens are present, the choice savings. Whatever the diagnostic strategy used, each ICU team should
of agents should be based on local patterns of antimicrobial susceptibil- monitor the adherence of their physicians to it and implement corrective
ity and anticipated side effects. Having a current and frequently updated measures, as needed.
that appropriate initial antibiotic treatment will be prescribed. The ■ FOCUSING THERAPY ONCE THE AGENT OF INFECTION IS IDENTIFIED
knowledge of local bacteriologic patterns can increase the likelihood
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choice should also take into account which therapies patients have Once the results of respiratory tract and blood cultures become avail-
recently received (within the past 2 weeks), striving not to repeat able, therapy can often be focused or narrowed, based on the identity
the same antimicrobial class, if possible. 255-257 of specific pathogens and their susceptibility to specific antibiotics,
Use of endotracheal aspirate surveillance cultures two or three-times in order to avoid prolonged use of a broader spectrum of antibiotic
weekly may also makes it possible to increase the proportion of patients therapy than is justified by the available information. 1,56,170,260,265-268 For
receiving initially appropriate antimicrobial therapy. 258-262 This strategy many patients, including those with late-onset infection, therapy can be
rests upon the observation that VAP caused by potentially multiresistant narrowed because an anticipated organism (such as P. aeruginosa and
pathogens is typically preceded by colonization of the oropharynx and Acinetobacter spp or MRSA) was not recovered or because the organ-
the proximal airways by the same strains. In order to be of clinical use ism isolated is sensitive to a narrower-spectrum antibiotic than used
in directing initial antibiotic therapy, surveillance cultures must be able in the initial regimen. For example, vancomycin and linezolid should
to detect this colonization rapidly and with high sensitivity, as false- be stopped if no MRSA is identified, unless the patient is allergic to
negative results would place the patient at risk for inappropriate therapy. β-lactams and has developed an infection caused by a gram-positive
Moreover, a focused antibiotic choice, with limitation of unnecessary microorganism. Very broad-spectrum agents, such as carbapenems,
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broad-spectrum drugs, requires a low number of false-positive surveil- piperacillin-tazobactam, and/or cefepime should also be restricted
lance results. Patients with a prolonged hospital stay and numerous pre- to patients with infection caused by pathogens only susceptible to
vious antibiotics will benefit the most. Thus, such a strategy can only be these agents. In case of infection caused by a piperacillin-susceptible
recommended when the local prevalence of multiresistant microorgan- P. aeruginosa strain, antimicrobial treatment should be streamlined
isms is high, when current empirical therapy is suboptimal and cannot to this specific drug. Similarly, in the absence of an infection caused

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