Isepamicin is a new
aminoglycoside antibiotic which possesses greater stability to
aminoglycoside-inactivating
enzymes compared with other available
aminoglycosides. In this prospective, randomised, open trial, the safety and efficacy of
intravenous administration of
isepamicin was compared with that of intravenous
amikacin in seriously ill adults with
nosocomial pneumonia or septicaemia. Each study
aminoglycoside was administered concurrently with
ceftazidime or
imipenem. Patients were randomised to receive
isepamicin 15 mg/kg once daily,
isepamicin 7.5 mg/kg twice daily or
amikacin 7.5 mg/kg twice daily. For patients with
nosocomial pneumonia, the proportions of patients in the intent-to-treat population (n = 130) who were clinically cured at the end of treatment were similar in each treatment group: 18/44 (41%)
isepamicin once daily; 19/45 (42%)
isepamicin twice daily; and 17/41 (42%)
amikacin. Corresponding results for the efficacy population (n = 58) were: 12/20 (60%)
isepamicin once daily; 14/21 (67%)
isepamicin twice daily; 9/17 (53%)
amikacin. In patients with septicaemia, clinical cure was achieved in 8/10 (80%) patients treated with
isepamicin once daily, compared with 8/13 (62%) patients who received
isepamicin twice daily, and 7/12 (58%) patients treated with
amikacin. For both diagnoses, there were no statistically significant differences between the treatment groups in clinical cure rate. The most commonly isolated target pathogen was Pseudomonas aeruginosa. For both
nosocomial pneumonia and septicaemia, the proportion of patients in the intent-to-treat population whose pretreatment valid target pathogens were eliminated was similar in each treatment group. In total, 51 patients (30%) died during study, mostly due to
disease progression or complications, or concurrent illness. All three treatment regimens were well tolerated. The proportion of patients experiencing at least one adverse event was 11%, 25% and 9% for
isepamicin once daily,
isepamicin twice daily and
amikacin, respectively. The incidence of
ototoxicity and nephrotoxicity was relatively low in both treatment groups.