Postantibiotic and post-beta-lactamase inhibitor effects of amoxicillin plus clavulanate.
The postantibiotic effect (PAE) of amoxicillin-clavulanate was studied for strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, and Escherichia coli. A PAE of approximately 2 h was seen for beta-lactamase-positive and -negative strains of S. aureus following 2 h of exposure to twice the MIC and did not increase at 16 times the MIC. The PAE observed with H. influenzae was clearly related to the growth rate of the organism. A PAE of 0.8 h was found for amoxicillin (four times the MIC) against a beta-lactamase-negative strain of H. influenzae (generation time, 26.3 min) and a PAE of 1.74 h was found for amoxicillin-clavulanate (twice the MIC) against a beta-lactamase-positive strain (generation time, 32.2 min). When the beta-lactamase-positive strain was growing more slowly (generation time, 120 min), the PAE of amoxicillin-clavulanate increased to > 3.32 h. The PAE of amoxicillin-clavulanate at 2/1 micrograms/ml on a beta-lactamase-producing strain of M. catarrhalis was > 2.9 h, and, as expected, the PAEs of twice the MIC on K. pneumoniae and E. coli were generally short (< 1 h). The post-beta-lactamase inhibitor effect (PLIE), determined after removal of only clavulanate, was also examined for beta-lactamase-positive strains. This was more prolonged (approximately 3 to 4 h) than the corresponding PAE for S. aureus, H. influenzae, and M. catarrhalis. The PLIE was related to the amount of beta-lactamase produced and required the presence of amoxicillin in the initial exposure period. These data may have implications for reducing the dosage of amoxicillin-clavulanate.
Thorburn
C E
CE
Department of Microbial Cell Sciences and Physiology, SmithKline Beecham Pharmaceuticals, Surrey, United Kingdom.
Molesworth
S J
SJ
Sutherland
R
R
Rittenhouse
S
S
D000658:Amoxicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000201:enzymology; D010406:Penicillins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000658:Amoxicillin