Once- versus twice-daily amikacin regimen: efficacy and safety in systemic gram-negative infections. Scandinavian Amikacin Once Daily Study Group.
Three hundred and sixteen patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open, randomized, comparative multicentre study with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12 h intervals. Two hundred patients were evaluated for efficacy and all 316 for safety. The efficacy of both dosage regimens was very good with a satisfactory clinical response in 90% of the patients. There were no significant differences between the two regimens regarding efficacy and safety. This was also confirmed in an analysis according to the principle of 'intention-to-treat' including all randomized patients. In 218 patients additional therapy, most commonly with piperacillin or ampicillin, was considered necessary. The mean peak serum concentration of amikacin was 40.9 mg/L in the once-daily group, which is 10 x MIC for most Gram-negative bacteria, compared to 24.4 mg/L in the twice-daily group, which is 6 x MIC. Mean trough serum concentrations after 24 h were 1.8 mg/L in the once-daily group and 3.1 mg/L after 12 h in the twice-daily group. These serum concentrations were often close to or just below the MICs of the isolated pathogens. Drug related adverse reactions were seen in 40 (13%) of the patients. Among the adverse reactions with possible or probable relation to amikacin were 20 nephrotoxic events, nine in the once-daily group and 11 in the twice-daily group. A multivariate analysis of selective causative factors and nephrotoxic events gave a low correlation for once- vs twice-daily amikacin therapy. Five ototoxic events were observed, three in the once-daily group and two in the twice-daily group. One patient in the once-daily group experienced nausea in connection with amikacin infusions.
Maller
R
R
Department of Infectious Diseases, University Hospital, Linköping, Sweden.
Ahrne
H
H
Holmen
C
C
Lausen
I
I
Nilsson
L E
LE
Smedjegård
J
J
D000583:Amikacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006309:Hearing / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged
D000583:Amikacin