Optimizing aminoglycoside therapy for nosocomial pneumonia caused by Gram-negative bacteria

Nosocomial pneumonia is a notable cause of morbidity and mortality and lead s to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with these infections, but few data on the doses and schedules required to achieve optimal therapeutic out comes exist. We analyzed aminoglycoside treatment data for 78 patients with nosocomial pnenmonia to determine if optimization of aminoglycoside pharma codynamic parameters results in a more rapid therapeutic response (defined by outcome and days to leukocyte count resolution and temperature resolutio n). Cox proportional hazards. Classification and Regression Tree (CART), an d logistic regression analyses were applied to the data. By all analyses, t he first measured maximum concentration of drug in serum (C-max)/MIC predic ted days to temperature resolution and the second measured C-max/MIC predic ted days to leukocyte count resolution. For days to temperature resolution and leukocyte count resolution, CART analyses produced breakpoints, with an 89% success rate at 7 days of therapy for a C-max/MIC of >4.7 and an 86% s uccess rate at 7 days of therapy for a C-max/MIC of >4.5, respectively. Log istic regression analyses predicted a 90% probability of temperature resolu tion and leukocyte count resolution by day 7 if a C-max/MIC of greater than or equal to 10 is achieved within the first 48 h of aminoglycoside therapy . Aggressive aminoglycoside dosing immediately followed by individualized p harmacokinetic monitoring would ensure that C-max/MIC targets are achieved early in therapy. This would increase the probability of a rapid therapeuti c response for pneumonia caused by gram-negative bacteria and potentially d ecreasing durations of parenteral antibiotic therapy, lengths of hospitaliz ation, and institutional expenditures, a situation in which both the patien t and the institution benefit.