Postantibiotic and post-β-lactamase inhibitor effects of amoxicillin plus clavulanate

Abstract

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 β-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 timex the MIC) against a β-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 β-lactamase-positive strain (generation time, 32.2 min). When the β-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 μg/ml on a β-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-β-lactamase inhibitor effect (PLIE), determined after removal of only clavulanate, was also examined for β- lactamase-positive strains. This was more prolonged (approximately 3 tn 4 h) than the corresponding PAE for S. aureus, H. influenzae, and M. catarrhalis. The PLIE was related to the amount of β-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.