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PMID: 1416886 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Adaptive resistance following single doses of gentamicin in a dynamic in vitro model.

Antimicrobial agents and chemotherapy ·Vol. 36 ·No. 9 ·1992-09-00 ·Pages 1951-7

Barclay ML, Begg EJ, Chambers ST

Abstract

Adaptive resistance is a phenomenon recently described for Pseudomonas aeruginosa and other gram-negative bacilli following exposure to aminoglycoside antibiotics. It is a reversible form of resistance which develops within 1 to 2 h of initial exposure to an aminoglycoside and disappears several hours after removal of the antibiotic. We investigated adaptive resistance in P. aeruginosa ATCC 27853 following single doses of gentamicin by using a dynamic in vitro model which mimics in vivo pharmacokinetics. The initial peak gentamicin concentrations were 2.5, 8, and 25 mg/liter, and these were followed by an exponential decay in the concentration, with a half-life of 2.5 h. The degree of adaptive resistance was greater and the duration was longer with higher initial gentamicin concentrations. Maximal adaptive resistance occurred between 2 and 10 h following 8 mg/liter and between 2 and 16 h following 25 mg/liter. Full recovery of susceptibility occurred at approximately 36, 39, and 43 h following 2.5, 8, and 25 mg/liter, respectively, at which times the gentamicin concentrations were extremely low. Longer dosing intervals for aminoglycosides may improve efficacy by allowing time for adaptive resistance to resolve.

MeSH Terms
Drug Resistance, Microbial/physiology Gentamicins/pharmacokinetics,pharmacology Half-Life Humans Models, Biological Pseudomonas aeruginosa/drug effects
Chemicals
Gentamicins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Barclay M L
Department of Clinical Pharmacology, Christchurch School of Medicine, New Zealand.
Begg E J
Chambers S T
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.36.9.1951
Published
1992-09-00
Pages
1951-7
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC192214
Subset
IM
External Links
PubMed source DOI: 10.1128/AAC.36.9.1951 PMC Full Text View journal details
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