Netilmicin Therapy of Gentamicin-Sensitive and -Resistant Gram-Negative Infections

Abstract

Netilmicin, a semisynthetic analog of gentamicin C1a, was administered to 24 patients for treatment of serious gram-negative infections. Among organisms isolated, 45% were gentamicin-resistant and 55% were gentamicin-sensitive. Cure was achieved in 7 of 8 bacteremias, 13 of 18 urinary tract infections, 2 of 3 wound infections, 0 of 3 pulmonary infections (two had bronchogenic carcinoma), and one infected ascites. In two patients, bacteremias were eradicated, but bacteremia due to a sensitive organism persisted in the presence of high urinary concentrations of netilmicin. The clinical and bacteriologic cure rate was 66%. Effective drug concentrations were demonstrated in serum, pleural fluid, and ascitic fluid. The drug also penetrated bile, although in lower concentrations. Serum creatinine elevations ≥ 0.5 mg/dl occurred in five patients (21 %) during treatment. Changes of 15 db or greater in two or more frequencies were noted in three of 13 patients with serial audiograms (23%). Reversible vestibular toxicity occurred in one patient who had prior gentamicin treatment, a single kidney, and peak serum netilmicin level of 18.5 μg/ml. Netilmicin is an effective aminoglycoside in the treatment of serious gram-negative infections, including many that may be due to gentamicin-resistant organisms. Both ototoxicity and nephrotoxicity occur under those circumstances predisposing to toxicity of other aminoglycosides.