netilmicin and Liver-Cirrhosis

Aminoglycosides are frequently used to treat sepsis in patients with liver disease. However, it has been suggested that cirrhotic patients are particularly sensitive to aminoglycoside-induced renal dysfunction. We investigated the efficacy and incidence of renal impairment with netilmicin plus mezlocillin compared with ceftazidime in 128 cirrhotic patients who required empirical treatment for sepsis. Renal impairment developed in 8 of 63 (13%) patients receiving netilmicin compared with 2 of 65 (3%) patients receiving ceftazidime (P < .05); it occurred despite regular monitoring of trough netilmicin levels. Renal impairment was present at the time of death in 1 of 13 (8%) patients treated with ceftazidime compared with 5 of 9 (56%) of the netilmicin patients (P < .05). Mortality rates were similar in the two groups (ceftazidime 20%, aminoglycoside 14%; P = NS). Renal dysfunction is significantly more frequent in cirrhotic patients treated with netilmicin but with careful attention to dosage and fluid management the clinical effect is likely to be relatively modest.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Gentamicins; Humans; Kidney; Liver Cirrhosis; Male; Mezlocillin; Middle Aged; Netilmicin; Penicillins; Prospective Studies; Sepsis

Topics: Anti-Bacterial Agents; Ceftazidime; Drug Therapy, Combination; Humans; Liver Cirrhosis; Netilmicin; Sepsis

The pharmacokinetics of netilmicin after intramuscular injection (2 mg/kg) was investigated comparatively in cirrhotic patients with or without ascites, and in healthy subjects. In patients with ascites, the same pharmacokinetic parameters were measured after the ascites had been cured. Twenty-four hours after intramuscular injection, the residual levels in cirrhotic patients were moderately higher than in controls, showing that liver failure or ascites did not significantly modify the pharmacokinetics of netilmicin. Serum concentrations were bactericidal. The ascitic fluid level was lower than the therapeutic range, but it was sustained for nearly 24 hours after intraperitoneal injection (2 mg/kg). These results indicate that netilmicin may be administered to cirrhotic patients without peritoneal infection using the same regimen as in healthy subjects. The peritoneal route may be preferable in case of peritoneal infection.

Topics: Adult; Aged; Ascites; Humans; Injections, Intramuscular; Injections, Intraperitoneal; Liver Cirrhosis; Middle Aged; Netilmicin