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Journal of Antimicrobial Chemotherapy (1995) 36, 803-814
© 1995 The British Society for Antimicrobial Chemotherapy

research-article

Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections

J. Blasera,*, H. P. Simmena, U. Thurnheerb, C. Königa and R. Lüthya

aDepartment of Medicine, D POL 40, University Hospital Zurich CH-8091 Zurich, Switzerland bAnna Seiler Haus, Inselspital Berne Berne, Switzerland

Received 22 November 1994; returned 12 April 1995; accepted 12 June 1995

*Tel: +41-(1)-2553618; Fax: +41-(1)-2554562

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of ≥20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a >25 µmol/L or >25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4mg/L). Half-lives of netilmicin determined between 1 and 8 h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P<0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined between 8 and 24 h in the od group (mean of 5.7 h, P<0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal.


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