Comparison of activity and beta-lactamase stability of cefotaxime with those of six other cephalosporins

Abstract

A study of the susceptibility to cefotaxime and six other cephalosporins in 213 nonselected strains of nine different bacterial species clearly showed that cefotaxime was the most active against aerobic gram-negative bacilli. The same pattern emerged with 84 cephalothin-resistant strains of five enterobacterial species, but the mean minimal inhibitory concentration values for all cephalosporins were about twofold higher in this group of strains. Cephalothin was the most active antibiotic against Staphylococcus aureus. The inoculum effect of 10 cephalothinresistant strains was relatively small, but it was most marked for cefamandole, as compared with that of three other niew cephalosporins, including cefotaxime. The susceptibility of these cephalosporins to beta-lactamases from 12 beta-lactamaseproducing enterobacterial strains was determined. Half of these were slightly active against cefotaxiine and had imilar activity against cefuroxime. Cefoxitin was not degraded at all, and cefamandole was the most susceptible. No correlation between beta-lactamase susceptibility and minimal inhibitory concentration values of different cephalosporins was found. Cefotaxime combined high intrinsic antibiotic activity with marked resistance to beta-lactamase inactivation.Several new cephalosporins became available and have been investigated in the last few years. Among these are cefamandole, which has high intrinsic antibacterial activity (2, 3), cefuroxime, which appears to be more active than cephalothin and shows resistance to inactivation by beta-lactamases (5,9), and cefoxitin, which combines a high degree of beta-lactamase resistance with activity against many anaerobes (10, 13). The new cephalosporin, cefotaxime (HR 756), has been studied in vitro (1,6,7,12) Preparation of cell-free extracts. CelLs were pregrown overnight in 5 ml of 3% brain heart infusion medium (Oxoid) at 370C in a shaker. A 1-ml portion of each culture was used to inoculate 300 ml of brain heart infusion medium, which was subsequently incubated at 370C. After 2 h of incubation, cephalothin was added at a final concentration of 25 jig/ml to induce beta-lactamase production. After another 3 h of incubation, cells were harvested by centrifugation, washed twice with 0.05 M sodium-potassium phospate buffer (pH 7.0), resuspended in 10 ml of phosphate buffer, and subsequently disrupted in a 100-W MSE ultrasonic disintegrator for 25 s. The sonicated suspen-

Comparative activities of 13 beta-lactam antibiotics

“…This difference was not observed with ceftazidime and N-formimidoyl thienamycin. A number of our S. faecalis strains showed lower cefuroxime MICs than have been reported by other workers (2,14,26). The cefotaxime MICs were also lower than the values reported by some other workers (3, 5-7, 18, 24, 26), but they were in excellent agreement with the results of Fu and Neu (4).…”

In vitro antibacterial activity of BMY-28142, a new extended-spectrum cephalosporin

“…It was the most potent compound against the Enterobacteriaceae, whereas its activity against Pseudomonas aeruginosa was not substantially different from that of ceftazidime and imipenem, which are currently known as the most potent 3-lactam compounds against this species (11). The antistaphylococcal activity of BMY-28142 was most similar to that of cefotaxime but remains below that reported for older cephalosporins (5 (3,7,12) and is most probably due to the derepression of the inducible cephalosporinase to constitutive synthesis (8). The overproduced P-lactamase then acts by hydrolyzing the cephalosporins or by merely trapping them, thereby creating an enzymatic penetrability barrier (13).…”

Ro 13-9904, a long-acting broad-spectrum cephalosporin: in vitro and in vivo studies

“…Ampicillin at a concentration of 100,ug/ml was added in the late log phase to those strains in which ,i-lactamase was seen to be inducible. Cells harvested by centrifugation were suspended in 10 Although cefotaxime and Ro 13-9904 showed almost equivalent activity against many species, Ro 13-9904 was more active than cefotaxime against isolates of Proteus mirabilis, N. gonorrhoeae, N. meningitidis, and H. influenzae.…”