Adaptive resistance following single doses of gentamicin in a dynamic in vitro model.
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.
Barclay
M L
ML
Department of Clinical Pharmacology, Christchurch School of Medicine, New Zealand.
Begg
E J
EJ
Chambers
S T
ST
D004352:Drug Resistance, Microbial / Q000502:physiology*; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000187:drug effects
D005839:Gentamicins