Interaction of New Cepbalosporins with ?-Lactamases and ?-Lactamase-Producing Gram-Negative Bacilli

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Abstract
Resistance to aminoglycosides and β-lactam antibiotics among gram-negative bacteria that cause nosocomial infections has become a serious problem in medical centers around the world. Resistance to these drugs commonly involves chromosomally or plasmid-mediated enzymes that modify or inactivate the drug. Recent developments in research on β-lactam antibiotics have resulted in compounds with increased stability to enzymatic inactivation and, in addition, with potent activity against many aerobic gram-negative organisms, including Pseudomonas. This study examines some of these new compounds, including cefoperazone and the aminothiazole oximes cefotaxime, ceftazidime, and ceftizoxime, in relation to their stability to cell-free β-lactamase preparations, activity against β-lactamase-producing strains, and susceptibility to increases in inoculum size. Overall, the aminothiazole oximes show a high degree of stability to β-lactamases produced by aerobic gram-negative rods, as well as a high order of activity against the producing organisms although all compounds tested are susceptible to inoculum effects. In contrast, cefoperazone is susceptible to β-lactamases, shows weak activity against β-lactamase-producing strains, and is highly susceptible to inoculum effects. None of the compounds tested shows good activity against β-lactamase-producing strains of Bacteroides fragilis.

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