The activity of cefotiam on beta-lactamase-producing bacteria in an in-vitro model.

The activity of cefotiam was tested in an in-vitro model simulating human serum pharmacokinetics. Bacterial strains used for inoculation either produced a penicillinase or a cephalosporinase. The rate of hydrolysis and the MICs of cefotiam were determined in comparison with those of ampicillin and cephalothin. The influence of these beta-lactamases on the killing kinetics and the degradation of cefotiam in the in-vitro model were then measured. Although all beta-lactamases hydrolyzed cefotiam, only the chromosomal cephalosporinases, especially those from Enterobacter and Klebsiella, reduced the elimination of the bacteria by degradation of the drug. A rough correlation between the hydrolytic activity and MIC could be demonstrated for cefotiam but not for ampicillin, while a correlation between killing ability and MIC only existed for strains with cefotiam MICs higher than 16 mg/l.