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


Blaser, J (1991). Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection. Journal of Antimicrobial Chemotherapy, 27(suppl C):21-28.

Abstract

The bactericidal efficacy of amikacin, isepamicin and netilmicin was studied against Pseudomonas aeruginosa and Serratia marcescens over a treatment period of 30 h using two one-compartment in-vitro models with differently designed culture compartments. High bacterial inocula were exposed to fluctuating drug concentrations, simulating human serum concentrations (t½ = 2 h) during clinical treatment. The same daily dose was administered as 1 h infusions given every 8 h or every 24 h, resulting in peak concentrations of 8 and 24 mg/l for netilmicin, and 24 and 72 mg/l for amikacin and isepamicin, respectively. Once-daily dosing was more bactericidal during initial treatment in the in-vitro models (P < 0·01) and at least as effective as thrice-daily dosing in preventing bacterial regrowth, despite a prolonged period of subinhibitory drug concentration before administration of the second dose. Lower ratios of peak concentration to MIC were needed to achieve bactericidal activity (> 99·9% reduction of cfu) after 24 h treatment against S. marcescens compared with P. aeruginosa (P < 0·01). All nine regimens providing peaks of at least four times the MIC were bactericidal against S. marcescens after 24 h exposure. In contrast, a bactericidal effect against P. aeruginosa occurred only during two of six experiments with peaks of four to nine times the MIC. Similar results were obtained in both in-vitro models of infection. These data suggest insufficient intrinsic activity of the aminoglycosides studied for single drug treatment of P. aeruginosa in the absence of host-defence mechanisms

Abstract

The bactericidal efficacy of amikacin, isepamicin and netilmicin was studied against Pseudomonas aeruginosa and Serratia marcescens over a treatment period of 30 h using two one-compartment in-vitro models with differently designed culture compartments. High bacterial inocula were exposed to fluctuating drug concentrations, simulating human serum concentrations (t½ = 2 h) during clinical treatment. The same daily dose was administered as 1 h infusions given every 8 h or every 24 h, resulting in peak concentrations of 8 and 24 mg/l for netilmicin, and 24 and 72 mg/l for amikacin and isepamicin, respectively. Once-daily dosing was more bactericidal during initial treatment in the in-vitro models (P < 0·01) and at least as effective as thrice-daily dosing in preventing bacterial regrowth, despite a prolonged period of subinhibitory drug concentration before administration of the second dose. Lower ratios of peak concentration to MIC were needed to achieve bactericidal activity (> 99·9% reduction of cfu) after 24 h treatment against S. marcescens compared with P. aeruginosa (P < 0·01). All nine regimens providing peaks of at least four times the MIC were bactericidal against S. marcescens after 24 h exposure. In contrast, a bactericidal effect against P. aeruginosa occurred only during two of six experiments with peaks of four to nine times the MIC. Similar results were obtained in both in-vitro models of infection. These data suggest insufficient intrinsic activity of the aminoglycosides studied for single drug treatment of P. aeruginosa in the absence of host-defence mechanisms

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Pharmacology
Health Sciences > Microbiology (medical)
Health Sciences > Infectious Diseases
Health Sciences > Pharmacology (medical)
Language:English
Date:1 January 1991
Deposited On:16 Oct 2018 15:24
Last Modified:15 Apr 2021 14:51
Publisher:Oxford University Press
ISSN:0305-7453
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/jac/27.suppl_c.21

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