The Association of Aminoglycoside Plasma Levels with Mortality in Patients with Gram-negative Bacteremia

To determine the association of aminoglycoside levels with mortality from gram-negative bacteremia, we analyzed the case reports of patients from four prospective, randomized, and controlled clinical trials of gentamicin, tobramycin, and amikacin. Twelve (13.5%) of 89 patients died. One (2.4%) death occurred in 41 patients with early (1-hr postinfusion) peak concentrations of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; nine deaths (20.9%) occurred in 43 patients with lower concentrations. Five (8.3%) deaths occurred in 60 patients with mean peak concentrations for the entire course of therapy of greater than 5 micrograms/ml of gentamicin and tobramycin and of greater than 20 micrograms of amikacin/ml; five (20.8%) deaths occurred in 24 patients with lower concentrations. Stepwise discriminant analysis showed that therapeutic early peak concentration was a significant factor in the presence of three other factors: severity of underlying illness, peak temperature, and initial leukocyte count. The results suggest the importance of achieving adequate early aminoglycoside levels in patients with gram-negative bacteremia.