A multicentric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intra-abdominal infections

Abstract

This multicentric, randomized, double-blind trial compared the efficacy and safety of netilmicin, 4.5 mg/kg od and 1.5 mg/kg tid, in patients with intra-abdominal infections. Of 114 patients enrolled, 57 patients (mean age 40.3 years) in the od group and 55 (mean age 36.8 years) in the tid group were evaluated for efficacy; 58 and 56 patients in corresponding groups were evaluated for safety. Among those evaluated for efficacy were 12 od-treated and 11 tid-treated patients with documented septicaemia, and 32 and 30 patients of respective groups with polymicrobial infections. Initially, 86 and 81 netilmicin-susceptible causative microorganisms were isolated in corresponding groups. Of these pathogens, 55% in the od group and 62% in the tid group were Escherichia coli. Daily dosage of netilmicin ranged from 3.70 to 4.71 mg/kg (mean 4.50) for the od group and from 3.06 to 4.76 mg/kg (mean 4.46) for the tid group. Duration of netilmicin therapy ranged from six to 13 days (mean 8.7 days) for od-treated patients and from seven to 16 days (mean 8.8 days) for tid-treated patients. Concomitant metronidazole was administered to 41 patients of the od group and 34 of the tid group; one patient in the tid group received clindamycin. Clinical and bacteriological responses were assessed, and peak and trough serum netilmicin levels were measured periodically, during therapy. Laboratory tests, including determinations of serum creatinine and blood urea nitrogen values, were performed throughout the trial. A clinical cure was achieved in 57/57 od-treated patients and 54/55 tid-treated patients; treatment failed in one tid-treated patient (1/55). In od and tid groups, 86/86 and 80/81 netilmicin-susceptible pathogens initially isolated were considered to be eliminated, respectively; one isolate (Esch. coli) persisted in the tid group. Mean peak serum netilmicin concentration in the od group was approximately two-fold greater than that in the tid group; mean trough serum netilmicin concentrations were similar for the two groups. Adverse reactions were limited to mild pain at the site of netilmicin administration in several patients in each treatment group. Netilmicin od and tid (alone or in combination with metronidazole) were similarly efficacious in the treatment of patients with appendicitis and other intra-abdominal infections caused by netilmicin-susceptible pathogens. Both dosage regimens of netilmicin were safe and well tolerated.

The Surgical Infection Society Guidelines on Antimicrobial Therapy for Intra-Abdominal Infections: An Executive Summary

“…In a large meta-analysis of patients with any type of gram-negative infection, this regimen was shown to be of equal efficacy compared to divided daily dose regimens, and possibly associated with fewer side effects [73]. Two prospective trials also found that once daily administration of aminoglycosides was efficacious in patients with intra-abdominal infections [74,75].…”

Clinical Issues Surrounding Once‐Daily Aminoglycoside Dosing in Children

“…45 In the most detailed data regarding microbiologic efficacy, 56 patients with documented bacterial infection received amikacin once/day either alone or in combination with another antibiotic. 52 Six classifications of infections were pneumonia (16 patients); chronic otitis (7); meningitis, bacteremia, septicemia (9); osteomyelitis (12); pyelonephritis (7); and peritonitis (5 …”

Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection

“…However, data from in-vitro and experimental in-vivo studies suggest that once-daily dosing of aminoglycoside might be at least as efficacious and potentially less toxic (Frame et al, 1977;Blaser, Stone & Zinner, 1985a;Gerber et al, 1989;Mattie, Craig & Pechere, 1989). Single-daily dosing of aminoglycosides has also been studied clinically (Powell et al, 1983;Hollender et al, 1989). However, a large number of patients need to be evaluated in comparative studies to detect clinically significant differences in either efficacy or toxicity.…”