Page 713 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

532 PART 4: Pulmonary Disorders

is most often proportional to infection severity. When that response MDR A. baumannii and/or P. aeruginosa), patients who were treated
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is absent or low, it might be logical to discontinue antibiotics earlier. with a combination of systemic antibiotics and nebulized colistin had a
Moreover, it is well-known that PCT levels reflect the inflammatory higher rate of favorable microbiologic outcome compared with patients
response intensity and are related to outcome. 231,311,312 Thus, adapting who were treated with systemic antibiotics alone (microbiologic eradica-
antimicrobial-treatment duration to PCT kinetics seems reasonable, and tion or presumed eradication 61% vs 38%), but there was no differences
has been demonstrated as useful in several randomized trials targeting in clinical outcome (51% vs 53%). In a retrospective case-control
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patients with acute respiratory infection, including five trials conducted study that included 86 patients with VAP due to multidrug-resistant
in the ICU. 219,222-226,230,313-319 GNB (predominantly A. baumannii) treated with a combination of IV
■ AEROSOLIZED THERAPY and aerosolized colistin compared with IV colistin alone, there was only
a trend towards improved rates of clinical cure, pathogen eradication,
Because insufficient dosing of antibiotics at the site of infection in and mortality in the patients who received aerosolized and IV colistin. 323
patients with VAP may lead to clinical and microbiological failures, Thus, although the results of recent investigations emphasize the
efforts to optimize pulmonary penetration of antimicrobial agents potential contribution of aerosolized antibiotics to treat VAP as an effi-
are warranted. Directly delivering the drug to the site of infection cient adjunctive therapy to intravenous antibiotics, the clinical impact
via aerosolization may represent a valid option, providing that this of such a strategy has not yet been definitively established. At present,
technique actually allows improved lung-tissue concentrations at the aerosolized antibiotics can only be recommended to treat patients with
infected site. This mode of administration, by achieving high pulmo- multidrug-resistant VAP, for which no effective intravenous antibiotics
nary antibiotic concentrations, could increase the antibacterial activity are available. Indisputably, large prospective trials are needed to evaluate
of concentration-dependent antibiotics, such as aminoglycosides, or the potential usefulness of this therapeutic modality.
restore the bactericidal activity of antibiotics in the case of infections
caused by pathogens of impaired sensitivity. Furthermore, by limiting PREVENTION
systemic exposure, it could also allow the administration of antibiotics
characterized by a high systemic toxicity, such as aminoglycosides and Because VAP is associated with increased morbidity, longer hospital stay,
polymyxins. increased health care costs, and higher mortality rates, prevention is a
Pooling the results of the five randomized controlled trials that major challenge for intensive care medicine. 1,328,329 A number of recom-
examined the potential benefit of inhaled or endotracheally instilled mendations for the prevention of VAP are empiric rather than based on
antibiotics for the treatment of patients with HAP/VAP, a statistically controlled observations, which make evaluation of the impact of such
higher success rate was demonstrated in patients receiving antimicrobial interventions difficult in this setting for several reasons: (1) the difficulty
agents via the respiratory tract. No difference in mortality, however, in obtaining an accurate diagnosis of VAP, that is, to distinguishing
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could be documented and the meta-analysis was based on a very limited patients with true infection from patients with tracheal colonization and/
number of patients. It should also be noted that the bronchial deposition or other pathologic processes: only patients who develop true VAP are
of aerosolized antibiotics might have rendered cultures of endotracheal likely to benefit from preventive measures; (2) the difficulty of precisely
samples falsely “negative,” which could have artificially increased the determining the impact of prophylactic measure on the overall mortal-
rate of success in patients randomized to aerosolized or endotracheally ity of a general ICU population, that is, to identify preventable deaths,
instilled antibiotics, casting some doubt on the validity of the results. directly attributable to VAP, among all deaths occurring in a population
Several recent studies, based on a new generation of nebulizers with of ventilated ICU patients; and (3) the difficulty of evaluating the conse-
improved technology, have renewed the interest in aerosolized antibiotic quences of a preventive measure on a potentially pathogenic mechanism,
therapy for patients with VAP. 321-324 In anesthetized piglets on prolonged for example, to evaluate the exact role played by prevention or reduction
mechanical ventilation for a severe experimental E coli bronchopneu- of tracheal colonization in modifying the development of VAP.
following aerosolization as compared to intravenous administration. ■ CONVENTIONAL INFECTION-CONTROL APPROACHES
monia, amikacin lung-tissue concentrations were markedly higher
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Seventy-one percent of lung segments were found sterile after two nebu- These measures should be the first step taken in any prevention pro-
lizations and 25 hours of treatment, whereas cultures of lung segments gram. The design of the ICU has a direct effect on the potential for
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were comparable in nontreated and intravenously treated animals. In nosocomial infections. Adequate space and lighting, proper functioning
a recent study using a new device with a vibrating plate and multiple of ventilation systems and facilities for hand washing lead to lower infec-
apertures to produce an aerosol of amikacin conducted in 69 patients tion rates. It should, however, be kept in mind that physical upgrading
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with GNB VAP, the authors found that the nebulized drug was well- of the environment does not per se reduce the infection rate unless per-
distributed in the lung parenchyma, with high tracheal and alveolar sonnel attitude and practices are improved. In any ICU, one of the most
levels but low serum concentration, below the renal toxicity threshold. important factors is the health care staff, including the number, quality,
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Moreover, aerosolized amikacin was well-tolerated, without any severe and motivation of medical, nursing, and ancillary members. The team
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adverse event, and patients who received amikacin twice daily required should include a sufficient number of nurses to minimize them moving
significantly less antibiotics than patients given placebo. 327 from one patient to another and to avoid having them working under
Data on the impact of aerosolized antibiotics active against gram- constant pressure. 333-336 The importance of personal cleanliness and
positive bacteria are scarce. In a placebo-controlled trial, Palmer, attention to aseptic procedures must be emphasized at every possible
et al. randomized 43 patients with purulent tracheobronchitis and opportunity. At the same time, unnecessarily rigid restrictions should be
Gram stain–identified microorganisms to receive aerosolized antibiotics avoided. The importance of personal cleanliness and attention to asep-
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(n = 19) or placebo (n = 24). The antibiotic was chosen according to tic procedures must be emphasized at every opportunity. It is clear that
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tracheal aspirate Gram-staining results (vancomycin for gram positive, careful monitoring, decontamination, and compliance with guidelines
gentamicin for gram negative). Antibiotic aerosolization led to faster for the use of respiratory equipment all reduce the incidence of noso-
resolution of clinical signs of pneumonia than placebo, fewer subsequent comial pneumonia. In particular, hand washing and hand rubbing
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VAP episodes, less bacterial resistance and use of systemic antibiotics, with alcohol-based solutions remain the most important components of
and perhaps accelerated weaning from mechanical ventilation. 322 effective infection control practices in the ICU. 141,335,338
Aerosolized polymyxin is also being used increasingly for treating A bacterial monitoring policy facilitates the early recognition of coloni-
patients with infections caused by multidrug-resistant GNB, mainly zation and infection, and has been associated with significant reductions
A. baumannii and P. aeruginosa, with mixed results. 323,324 In a randomized in nosocomial infection rates. The focal point for infection control
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trial that included 100 patients with VAP due to GNB (predominantly activities in the ICU is a surveillance system designed to establish and

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