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Because there are few persuasive data for selecting one semisynthetic penicillin or cephalosporin over another for treatment of serious staphylococcal infections, 118 recent clinical isolates of Staphylococcus aureus were studied to determine to what extent the presence of fl-lactamase affected the relative anti-staphylococcal activity of six penicillins and seven cephalosporins. In addition, the effect of inoculum was studied for its possible effect on the anti-staphylococcal activity of the 13 ,8-lactam antibiotics. By all criteria, methicillin and nafcillin were clearly more resistant to both the inoculum effect and the production of staphylococcal ,B-lactamase, whereas benzylpenicillin and cephaloridine (especially benzylpenicillin) were the most susceptible to these effects. Cephazolin was clearly more susceptible to staphylococcal #-lactamase and heavy inocula than the other cephalosporins (with the exception of cephaloridine), whereas cephalothin was the most resistant cephalosporin to these factors. The minimal inhibitory concentration for benzylpenicillin for tests with undiluted inoculum, compared to results with inoculum diluted 10-4, differed by a factor up to 16,384, whereas with methicillin and nafcillin the differences were rarely more than twofold. Ratios for the other 10 antibiotics fell between these extremes. These results suggest that methicillin or nafcillin is most stable to staphylococcal ,-lactamase, and that benzylpenicillin and cephaloridine are the most susceptible.

The susceptibilities of 36 recent isolates of Staphylococcus aureus and 35 recent isolates ofStaphylococcus epidermidis were determined against each of 65 antimicrobial agents and against two of them in combination. Rifampin was the most active of all the agents tested against both S. aureus and S. epidermidis. Among the penicillins, cloxacillin, dicloxacillin, and nafcillin were most active, although benzylpenicillin and phenoxymethyl penicillin were more active against susceptible strains. Cephaloridine was the most active of the cephalosporins, and sisomicin was the most active aminoglycoside. Minocycline was more active than the other tetracycline analogues tested. Among the macrolide-lincomycin compounds in clinical use, clindamycin was more active, and lincomycin was less active than erythromycin. The synergy of trimethoprimsulfamethoxazole was more striking against S. aureus than against S. epidermidis. The median minimal inhibitory concentrations of the penicillins, cephalosporins, and aminoglycosides were lower against S. aureus, whereas the minimal inhibitory concentrations of the tetracyclines were lower against S. epidermidis.A large number of new natural and semisynthetic antibiotics with anti-staphylococcal activity have been introduced recently. This study was performed to compare their activities with those of other compounds that have been available for several or more years. The desirability of having comparative data on the same organisms from one laboratory, obtained by a uniform method, is obvious.Tests were performed on both Staphylococcus aureus and Staphylococcus epidermidis for the purpose of observing possible differences, and also to obtain information that would be potentially useful in clinical medicine. MATERIALS AND METHODSSixty-five antimicrobial preparations and two of them in combination (trimethoprim plus sulfamethoxazole in a ratio of 1:16; this was selected for convenience of making dilutions for the test -a ratio of 1:20, which has been suggested as the trimethoprim/sulfamethoxazole ratio in blood, might have been used, but no great differences in results were anticipated by using 1:16) were tested for antibacterial activity against 36 strains of S. aureus and 35 strains of S. epidermidis (in several instances, only 12 strains of S. aureus and 12 or 32 strains of S. epidermidis were tested). The antimi- Tables 1 through 3; also shown in these tables are the abbreviations for each compound, as used in the figures.The organisms tested were all recent clinical isolates at Boston City Hospital, provided by A. Kathleen Daly and Alice McDonald, and identified on the basis of colonial morphology, Gram stain, coagulase reaction, and mannitol fermentation tests. The susceptibility testing was done by the agar dilution method using Mueller-Hinton agar and the inocula replicator of Steers et al. (8), using as inoculum 10-3 dilutions of overnight cultures. Plates were read for inhibition of growth after 18 h of incubation at 37 C and compared with a refrigerated, inoculated control (fo...

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