ODENHOLT I, LOWDIN E, CARS O; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-2088.

Dep. of Infectious Diseases, University Hospital, Malmo, Sweden

The efficacy of beta-lactam antibiotics is mainly dependent on the T>MIC. However, the exact fraction of the dosage interval during which MIC should be exceeded for optimal efficacy is not known. The aim of the present investigation was to compare the pharmacodynamic effects of a new PE formulation of AMX/CA with conventional doses against different strains of H. influenzae(HI) in an in-vitro kinetic model using simulated kinetics of the different dosage regimens. METHODS: Five clinical isolates of HI were exposed to A/C simulating the peak levels achieved after a dose of 875/125 mg b.i.d. and 500/125 mg t.i.d. with a T1/2 of 1 h. The MICs of AMX/CA for the isolates were 0.5-0.75 mg/l. In the experiments with the PE compound (2000/125 mg b.i.d.), the concentrations after 1124mg/125 mg of A/C (immediate release) and 875mg amoxicillin (slow-release) b.i.d. were simulated. RESULTS: Neither of the dosing regimens used in our study, in which T>MIC of A was < 50% was sufficient to achieve a complete bactericidal effect during the first 24 h of treatment. After 24 h, there was a tendency of better efficacy with the 500/125mg t.i.d regimen for all strains except one, as compared to the 875/125 b.i.d. regimen, with differences in cfus of 1.7 to 3.3 log10. However, these differences did not reach statistical significance. When the concentration of the PE AMX/CA was simulated, giving a longer T>MIC (80%) of AMX, complete killing of all strains was obtained after 24 h even though the concentration of C was only present for 45% of the dosing interval. CONCLUSION: Neither of the older dosing regimens was sufficient to kill HI after 24 h. However, when the kinetics of PE AMX/CA was simulated complete killing was achieved.

Publication Types:

• Meeting Abstracts

Keywords:

• Amoxicillin
• Chemistry, Pharmaceutical
• Clavulanic Acid
• Haemophilus influenzae
• In Vitro
• Kinetics
• Microbial Sensitivity Tests
• administration & dosage

Other ID:

• GWAIDS0030563

UI: 102270200

From Meeting Abstracts