Variation in the potentiation of β-lactam antibiotic activity by clavulanic acid and sulbactam against multiply antibiotic-resistant bacteria

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Abstract
Using a broth microdilution method, we studied 120 strains of β-lactamase-producing clinical isolates to determine the potentiating effect of clavulanic acid and sulbactam (both β-lactamase inhibitors) on the antibacterial activity of a variety of β-lactam antibiotics. All antibiotics were tested alone and in combination with each inhibitor simultaneously using low (105 cfu/ml) and high (107 cfu/ml) inocula. Against the strains of Escherichia coli and Haemophilus influenzae the addition of both inhibitors significantly potentiated the activity of most antibiotics at the low inoculum. At the high inoculum, however, this effect was abrogated against E. coli and most strains of H. influenzae. Antibiotic activity was significantly enhanced by the inhibitors at both inoculum sizes with Bacteroides fragilis. Antibiotic resistance of Pseudomonas aeruginosa was little affected by the inhibitors. Among methicillin-resistant staphylococci, antibiotic potentiation by the inhibitors was more significant for Staphylococcus aureus than the coagulase-negative staphylococci.