Role of beta-lactamase of methicillin-susceptible Staphylococcus aureus in resistance to first-generation oral cephems both in vitro and in vivo.
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| Abstract |
Cefaclor, among the oral cephalosporins tested, showed the largest inoculum effect with respect to MIC values for 61 clinical isolates of methicillin-susceptible Staphylococcus aureus, including 39 beta-lactamase producing strains. These 39 strains were divided into eight type A, 29 type B or C, and two type D producers, by comparisons of specific activities to three substrates. Two producers, one each of types A and C, were further studied to investigate the effect of beta-lactamase on staphylococcal resistance to several beta-lactams. Concentrations of cefaclor and cephalexin in cultures of these strains decreased rapidly, whereas hydrolysis of these drugs by the purified beta-lactamases was moderate to low as detected by spectrophotometric assay. Cefaclor showed high affinities for penicillin-binding proteins 1, 2, and 3 of both beta-lactamase producers and their respective penicillinase-non-producing mutants. In experimental intraperitoneal infections in mice, cefaclor was therapeutically effective against both mutants, showing 50% effective doses of less than 10 mg/kg/dose. In contrast, it was not satisfactory against the parent strains, requiring greater-than-10-fold increases in concentration for the same degree of survival. We concluded that resistance to first-generation oral cephems seen both in vitro and in vivo was due mainly to the beta-lactamase production.
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| Authors | T Takenouchi, Y Utsui, S Ohya, T Nishino |
| Journal | The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 34 Issue 6 Pg. 909-20 (Dec 1994) ISSN: 0305-7453 [Print] England |
| PMID | 7730234 (Publication Type: Journal Article) |
| Chemical References |
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