In 60% of patients with VAP, the sputum culture is polymicrobial, but regardless of whether the infection is single agent or mixed, there is a core of organisms that account for greater than 90% of VAP. Therefore empiric therapy is directed at this group of pathogens. Enteric gram-negative bacteria and Staphylococcus aureus make up the bulk of the core group, and Streptococcus species contributes to about 10-20% of VAP. The specific gram-negative bacteria vary depending on the colonizing flora of the individual ICU. Highly prevalent organisms include Pseudomonas aeruginosa, Acinetobacter species, Proteus, Haemophilus, Escherichia coli, Enterobacter cloacae, Klebsiella, Citrobacter, and Moraxella. Anaerobes and fungi are uncommonly seen in VAP, less than 5% each in endotracheal cultures, except in the context of bulk aspiration of gastric contents. Viral pathogens have not been a significant source of VAP adult ICUs, but have been found in 20% of pediatric VAP.

As the diagnosis of VAP is often uncertain, and because it can be impossible to separate colonizing bacteria from infecting bacteria, initial therapy usually consists of empirical coverage of the core bacteria, with modification for resistant organisms if found on endotracheal culture. Invasive culture techniques can be used if the patient does not respond to empirical therapy, especially if resistant organisms are suspected or if other sites of infection have been ruled out.

What is the empiric antibiotic treatment for VAP and what is the recommended length of treatment?

Given the broad spectrum of coverage needed for the above organisms, combination therapy is usually favored for critically-ill patients, consisting of a beta lactam agent plus an aminoglycoside. This combination has the advantage of coverage for most multi resistant gram-negative organisms and methicillin sensitive S. aureus. If the patient is known to be colonized with methicillin resistant S. aureus, empiric therapy with vancomycin is warranted in severe VAP: likewise colonization with a known multi-resistant gram-negative enteric bacteria in VAP warrants use of extended spectrum gram-negative agents such as meropenem, and known aspiration of gastric contents with the development of VAP warrants anaerobic coverage. Aminoglycoside therapy may not be suitable for patients with impaired renal function; a fluoroquinolone may be used in these patients. The quinolones have an additional theoretical advantage, in that this class of drugs penetrate into the bronchial secretions much better than the aminoglycosides. Non-critically ill patients can be treated with monotherapy, using a beta lactam agent alone. Penicillin allergic patients can be treated with clindamycin plus quinolone or aminoglycoside. Endobronchial instillation of aminoglycoside has been used in small trials, with inconclusive results.

Duration of therapy is controversial, but most published trials have continued treatment for 10 to 14 days. Longer courses of therapy are recommended by the American Thoracic Society for immunocompromised or severely ill patients.

Question Author: Edward Kelly, MD, Department of Surgery, Brigham and Women's Hospital