Beta-lactamase-positive strains of Haemophilus influenzae: susceptibility to and inactivation of beta-lactam antibiotics

Susceptibility and time-kill studies were done with low and high inocula of both beta-lactamase-positive and -negative strains of Haemophilus influenzae with cefamandole, ampicillin, cefoperazone, mezlocillin, moxalactam, and ceftriaxone. Bioassay was done to test for antibiotic inactivation by beta-lactamase-positive strains. All six antibiotics were highly active against the low inoculum (10(4) to 10(5) colony-forming units/ml) of beta-lactamase-negative strains; ceftriaxone, moxalactam, and cefoperazone were equally active against the same inoculum concentration of beta-lactamase-positive strains. In contrast, cefamandole, mezlocillin, and ampicillin were less active against the low inoculum of beta-lactamase-positive H influenzae. A marked inoculum effect occurred with the high inoculum (10(7) to 10(8) CFU/ml) with all six antibiotics, regardless of beta-lactamase production. In time-kill studies, marked differences in bacterial killing resulted after low and high inocula. Ampicillin, cefamandole, cefoperazone, and mezlocillin were rapidly inactivated by the high inoculum of beta-lactamase-positive H influenzae.