Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 ,ug or less of cefazaflur per ml inhibited almost all strains of Staphylococcus aureus, Escherichia coli, Klebsiella, and Proteus mirabilis. The drug was less active against Enterobacter and indole-positive Proteus, and 7.5 ug of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 ug of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against Pseudomonas. The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 ug of cefazaflur per ml killed all strains of E. coli, whereas with the higher inoculum, 7.5 ,g of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.Cefazaflur, SKF 59962, is a new parenteral cephalosporin containing a 7-trifluoromethylthioacetyl group at the 7-acyl position (3). Drug concentrations in the serum of experimental animals were found to be similar to those obtained with comparable doses of cephalothin, although cefazaflur demonstrated greater in vitro activity than cephalothin against some genera of organisms, including isolates of Enterobacter (1).The purpose of this study was to evaluate the antibacterial activity of cefazaflur in in vitro studies utilizing several different test conditions.MATERIALS AND METHODS Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using Mueller-Hinton (MH) broth (MHB; Difco) and nutrient broth (NB; Difco) according to previously described methods (4, 6). In broth dilution studies, the MBC was defined as the lowest concentration of drug yielding 10 colony-forming units or less when about 0.005 ml of broth from each clear tube was subcultured onto agar without antibiotic. Two different inocula containing 106 and 108 viable organisms per ml were used. Agar dilution MICs were determined with Mueller-Hinton agar (MHA) and nutrient agar (NA). The MIC in agar, obtained using a Steers replicator (5) RESULTSAgar dilution. The results of studies determined in agar are presented in Table 1. There were no consistent differences among results obtained with various species of Enterobacter and indole-positive Proteus isolates, and the results are composited for each genus. The drug had negligible ac...

,B-Lactamase production and MIC determinations for penicillin, methicillin, and cephalothin were assessed for 67 strains of Staphylococcus saprophyticus and correlated with results of disk diffusion susceptibility testing. Fifty-five (82%) of the 67 strains produced 14-lactamase, and 40 (77%) of these ,B-lactamase-producing strains were susceptible (zone size, >29 mm) by disk diffusion techniques. Although the range of zone sizes for ,-lactamase producers was broad (26 to 36 mm), all 38 strains with a zone size of <31 mm by disk diffusion testing were 3-lactamase producers compared with 17 (59%) of 29 with larger zone sizes (P = 0.0000008). The median penicillin MIC for 12 S. saprophyticus strains was 0.25 ,g/ml and was not related to (-lactamase production. Although the methicillin MICs for 15 strains were in the susceptible range (4.0 ,Ig/ml), interpretation of disk diffusion testing for oxacillin varied greatly among laboratories using identically prepared media and standardized techniques. Criteria presently used to define susceptibility of Staphylococcus aureus to penicillin and oxacillin by disk diffusion are inappropriate for S. saprophyticus. The clinical significance of the l-lactamase produced by these strains needs further evaluation.Staphylococcus saprophyticus, a coagulase-negative staphylococcus, is a common cause of acute urinary infections in young women (3,6,15). Unlike most other coagulase-negative staphylococci, S. saprophyticus strains are reported to be uniformly susceptible to most antibiotics active against gram-positive organisms (3,9,15). Yet, in a recent study of urinary infections with this organism among college women (6), we found that the majority of strains were not susceptible to penicillin and methicillin by disk diffusion (DD) techniques, but were susceptible to cephalothin. To explain this observation, we assessed the prevalence of P-lactamase production among strains of S. saprophyticus, determined the MICs of penicillin, methicillin, and cephalothin for these strains, and correlated these results with susceptibility testing by DD. MATERIALS AND METHODS Sixty-seven S. saprophyticus strains isolated from ambulatory patients with acute urinary infections were evaluated.

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