The activity of cefamandole and cefuroxime against oxacillin-resistant Staphylococcus epidermidis was studied in vitro to determine whether there was any relationship between oxacillin resistance phenotypes and cephalosporin activity. Oxacillin resistance phenotypes were determined by efficiency-of-plating studies on Mueller-Hinton agar containing oxacillin, with and without NaCl, and incubated at 30 and 35°C. On the basis of MIC and MBC determinations, cefamandole was more active than cefuroxime against oxacillin-resistant S. epidermidis. Although temperature had minimal effect on the activity of either cefamandole or cefuroxime, NaCl significantly decreased the activity of cefuroxime but not of cefamandole. Neither cephalosporin consistently produced -99.9% bactericidal activity within 24 h in timed killing-curve studies. No consistent relationship was observed between cefamandole or cefuroxime activity and oxacillin resistance phenotype.According to current standards for antimicrobial susceptibility tests of the National Committee for Clinical Laboratory Standards, all methicillin-resistant staphylococci should be considered resistant to cephalosporins (8). In recent studies, however, cefamandole has been shown to be active in vitro against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis (3, 13). Furthermore, when compared with cefazolin for prophylaxis in cardiac surgery patients, both cefamandole (M. R. Petracek, A. B. Kaiser, J. W. Lea, D. S. Kernodle, and A. C. Roach, Clin. Res. 35:21a, 1987) and cefuroxime have been associated with significantly fewer postoperative staphylococcal infections (11). In contrast, cefamandole has not been consistently effective against methicillin-resistant staphylococci either in experimental models of infection (6) or in clinical studies (2, 4). These discrepant results may be due to differences in degrees of methicillin resistance among strains of staphylococci (7). Recently Hartman and Tomasz identified three phenotypes of methicillin-resistant S. aureus: homogeneous, heterogeneous, and thermosensitive heterogeneous (5). Studies identifying phenotypes of methicillin-resistant S. epidermidis, however, have not been done. The objectives of our study were first to determine whether methicillin (oxacillin) resistance phenotypes similar to those identified for methicillin-resistant S. aureus exist among oxacillinresistant S. epidermidis and second to determine whether the resistance phenotype relates to the activity of cefamandole and cefuroxime against oxacillin-resistant S. epidermidis.
MATERIALS AND METHODSOrganisms. Blood culture isolates, identified specifically as S. epidermidis, were taken from 40 patients. Each isolate was initially characterized as being oxacillin resistant by disk diffusion susceptibility testing (16). * Corresponding author. Antimicrobial agents and susceptibility testing. Oxacillin was obtained from Sigma Chemical Co., St. Louis, Mo.; cefamandole was obtained from Eli Lilly & Co., Indianapolis, Ind.; and cefuroxime was ...