In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 42, No. 6 ( 1998-06), p. 1370-1374
Abstract:
In vitro studies were designed to investigate the influence of peak drug concentration ( C max ), the area under the concentration-time curve (AUC), and, consequently, the trough concentration on the bactericidal effects of gentamicin against Enterobacter cloacae (MIC, 0.5 mg/liter) by simulating bolus versus infusion administration and bolus dosing with altered drug clearance. Bacteria in the lag phase were exposed to gentamicin concentration-time profiles modelling either bolus or infusion dosing (AUC constant, C max changing) with 30-min postdose peak concentrations ( C peak30 ) of 4, 6, 8, and 10 mg/liter or bolus dosing with normal and double drug clearance ( C max constant, AUC changing) corresponding to normal clearance profiles with C peak30 of 6 and 8 mg/liter. Exposure to gentamicin caused early bactericidal effects apparent by 2 h, followed by variable bacteriostatic and recovery phases. Exposure to bolus profiles resulted in greater bactericidal activity than the corresponding infusion profile up to a C peak30 of 8 mg/liter. At a C peak30 of 10 mg/liter, there were no differences in bactericidal effect. Double clearance profiles had a reduced bactericidal effect at 6 mg/liter compared to the corresponding normal clearance profile, but no differences in bactericidal effect were observed for 8-mg/liter double and normal clearance profiles. These results suggest that the initial exposure (i.e., 0 to 30 min) is a more important determinant for bacterial killing than the AUC or trough concentration for this bacterium. Subject to confirmation of these findings with other gram-negative bacteria, to optimize aminoglycoside efficacy the initial exposure ( C max ) should be maximized by giving higher doses or bolus administration at intervals which may not produce detectable trough concentrations. Clinical trials with a broad range of patients, especially those with higher clearance, would confirm these in vitro observations and define optimal dosing recommendations.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.42.6.1370
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
1998
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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