Prospective Evaluation of the Effect of an Aminoglycoside Dosing Regimen on Rates of Observed Nephrotoxicity and Ototoxicity

摘要: The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients suspected or proven gram-negative bacterial infections a randomized, double-blind clinical trial. Patients who received therapy for ≥72 h were evaluated toxicity. also concomitant antibiotics as deemed necessary treatment their infection. Plasma aminoglycoside concentrations, prospective dosage adjustment, serial audiologic renal status evaluations performed. probability occurrence nephrotoxic event its relationship to doses daily exposure served the main outcome measurement. One hundred twenty-three enrolled study, 83 receiving at least 72 h. For 74 plasma concentrations available analysis, formed group evaluable primary infectious diagnosis study bacteremia sepsis, respiratory infections, skin soft tissue urosepsis pyelonephritis. Of toxicity, 39 twice 35 once placebo 12 later. Nephrotoxicity occurred 6 (15.4%) 0 daily. schedule administration, use vancomycin, area under concentration-time curve (AUC) found be significant predictors by multivariate logistic regression analysis (P ≤ 0.001). time significantly influenced vancomycin Cox proportional hazards modeling 0.002). results demonstrate that both are on which is administered well vancomycin. Furthermore, this risk modulated AUC exposure. These data suggest has predictably lower causing than administration.