Aerosolized antibiotic therapy: a forward aerial assault or forced contingency for ventilator-associated pneumonia?

The increasing prevalence and complexity of multipledrug-resistant (MDR) organisms in nosocomial infections have fueled interest in novel therapeutic approaches. Adjunctive aerosolized antibiotic (AAA) therapy for pneumonia has gained popularity, supported by apparent advantages of higher pulmonary antibiotic concentrations and lower systemic exposure. Balanced by a paucity of highlevel evidence, consensus statements recommend AAA therapy be considered in patients with MDR pathogens not responding to intravenous therapy.1,2 The most commonly reported aerosolized agents, aminoglycosides and colistin, have narrow therapeutic indexes and poor pulmonary penetration3,4 associated with systemic administration. However, these agents often have higher bactericidal potencies and retained in vitro susceptibility against many MDR pathogens (eg, Pseudomonas aeruginosa and Acinetobacter species).5 These qualities, in combination with their concentration-dependent pharmacodynamic properties (ie, the higher the antibiotic concentration to bacterial minimum inhibitory concentration, the greater bacterial killing), make intermittent aerosolization of these agents attractive. Although there has been some progress in formal aerosolized antibiotic drug development intended for the treatment of pneumonia in critically ill patients,6 prospective studies evaluating the effects on patient outcome have been limited by underpowered design, lack of control group, heterogeneous definitions for pneumonia, variable treatment regimens, poorly described aerosolization methods, and concomitant antibiotic therapy.2 Published metaanalyses nicely frame many of these limitations.7,8 Consequently, most recent reports and series have described the use of aerosolized aminoglycosides or colistin as adjunctive or salvage therapy in patients with pneumonia recurrence or pneumonia caused by MDR pathogens.9–13