Growth Curves, Microscopic Morphology, and Subcultures of Beta-Lactamase-Positive and -Negative Haemophilus influenzae Under the Influence of Ampicillin and Cefamandole

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Abstract
In contrast to the results obtained with ampicillin, the minimum inhibitory concentrations of cefamandole against Haemophilus influenzae were within the same range (0.5 to 1.5 μg/ml) whether or not the strains were beta-lactamase producers. The minimum bactericidal concentrations were somewhat higher for beta-lactamase-positive strains (6.4 μg/ml) than for negative strains (1.2 μg/ml). In a culture with high initial microbial density, monitored by recording optical densities, the addition of 10 μg of cefamandole per ml brought about rapid lysis of a beta-lactamase-negative strain. Observation of a beta-lactamase-positive strain revealed, in the early part of the growth curve, absence of lysis and an increase of biomass similar to that observed in a drug-free control curve. In contrast to the results obtained with ampicillin, the culture consisted uniformly of spherical forms, probably in the process of division, which were capable of generating colonies. When the microbial density exposed to cefamandole was increased still further, persistent bacillary forms were observed, and after 24 h hydrolysis had eliminated every trace of microbiologically active cefamandole.