Adjunctive Aerosolized Antibiotics to Treat Ventilator-Associated Pneumonia: A Clinical Conundrum Continues.

Ventilator-associated pneumonia (VAP) continues to be a major complication of critical illness, and patient outcomes are often suboptimal. Approximately one third of patients receiving intravenous antibiotics alone will fail therapy. In addition, an increase in multidrug-resistant strains of Pseudomonas, Acinetobacter, and enterobacteriacae (eg, carbapenemase-producing Klebsiella) limits therapeutic choices. It is not clear why so many patients fail therapy, but one factor may be that many antibiotics commonly used for VAP, such as -lactams, aminoglycosides, and vancomycin, have relatively poor lung penetration.1 Thus, adding intratracheally administered antibiotics makes intuitive sense in an attempt to increase antibiotic concentrations at the site of infection. The term “intratracheal” encompasses all methods of delivering antibiotics directly to the lungs, but the most common practice is aerosolization (some prefer “nebulization” or “inhalation”. I will use “aerosolization” generically in this editorial.) Adding aerosolized antibiotics to intravenous antibiotics to treat severe pulmonary infections has been studied intermittently since the 1960s.2,3 However, since the turn of the millennium, there has been a sharp increase in publications in this area. Most have described aerosolized colistin or aminoglycosides as adjunctive therapy for multidrug-resistant Gram-negative VAP. Less commonly, aerosolized cephalosporins have also been used. An anticipated side benefit of this route of administration may be a decrease in systemic adverse events (such as nephrotoxicity with colistin or aminoglycosides) because aerosolization does not usually result in significant serum concentrations in patients with normal renal function.2,3 Unfortunately, there are many unanswered questions regarding the use of aerosolized antibiotics for VAP. Most notably, the vast majority of publications to date have described retrospective, observational studies without control groups. There are no large randomized controlled trials comparing intravenous plus aerosolized antibiotics with intravenous therapy alone. Fortunately, some recent studies have been more rigorous (eg, using matched control