Feasibility of aerosolized colistin in the era of escalating drug-resistant Pseudomonas pneumonia: pressing need for validation clinical trials

Excerpt

Drug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species are common pathogens encountered in critically ill patients with bacterial pneumonia [1]. Colistin is cationic lipopeptide, a polymyxin drug that fell out of favor due to concerns over neurotoxic and nephrotoxic side-effects [2]. Alternate route, especially topical applications that directly deliver the drug to terminal respiratory tract, appeared desirable. Two chief concerns regarding topical drug therapy were development of drug resistance and tolerability of inhaled chemicals that may trigger serious irritation and promote potentially deleterious inflammation of respiratory tract. Given that topical administration results in a gradient of antimicrobial drug concentration from central to peripheral airways, there is substantial concern regarding induction of antimicrobial resistance [3]. Whereas case reports and case series have confirmed that resistant organisms can emerge during therapy [4], careful examination during randomized clinical trials has not found emergence of drug-resistant organisms in treated patients to be a particularly significant issue [5]. …