Cefoxitin, a New Semi-synthetic Cephamycin: An In-vitro and In-vivo Comparison with Cephalothin

Section: Resultsmentioning

confidence: 85%

mentioning

confidence: 99%

Antibacterial Activity of Selected Beta-Lactam and Aminoglycoside Antibiotics Against Cephalothin-Resistant Enterobacteriaceae

Lewis

Meyer

Kraus

1976

“…These beta-lactamases possess a high degree of activity against CM. Although the ability of CX to act as an inducer of beta-lactamases has been reported previously (4,10,12,20,25), its superiority over similar drugs as an inducer and the enhanced activity of the induced enzyme for CM has not been reported. This phenomenon resembles methicillin induction of penicillinase in Staphy- (5,14,18).…”

Section: Discussionmentioning

confidence: 97%

Emergence of Resistance to Cefamandole: Possible Role of Cefoxitin-Inducible Beta-Lactamases

1979

170

102

Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147 Enterobacteriaceae for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of Enterobacter, indole-positive Proteus, and Serratia. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.Cefamandole (CM;6,11,26) and cefoxitin (CX; 3, 24) possess a greater spectrum of antibacterial activity than previously marketed cephalosporins. Possible bases for the expanded spectrum of these new compounds include their resistance to a variety of beta-lactamases and/ or greater intrinsic activity, i.e., better penetration into the cell and attachment to target proteins (3,5,11,20,22,26). However, results of a recent study with these new drugs showed significant discrepancies between in vitro and in vivo tests, especially with CM (9). Animals infected with organisms appearing to be susceptible to CM in vitro failed to respond to therapy with the drug. Furthermore, in vivo selection of resistant mutants was observed in several instances. The purpose of this investigation was to analyze strains used in the previous study to determine if beta-lactamase production might be responsible for the discrepancies observed. MATERIALS AND METHODSAntibiotics. All drug solutions (weight compensated for purity) were prepared the day of use. Working standards were prepared from the following anti- Beta-lactamase assays. Beta-lactamase activity was evaluated by direct spectrophotometric methods (19) on whole cells. Cells from a 24-h Mueller-Hinton agar culture (Difco) were suspended in phosphate buffer (pH 7) so as to give 109 colony-forming units per ml. Fresh drug solution was added to the cell suspension to give a final concentration of 100 ,M, and, after incubation for 4 h at 37°C in air, the cells were removed by filtration (Millipore membrane filter). Plate counts of the drug-cell suspensions indicated no loss in viability during the 4-h incubation. The concentration of active drug remaining in the filtrate was determined by reading the optical density of the solution at the wavelength of maximal absorption associated with the beta-lactam ring (Beckman DB-GT). This wavelength varied between 255 and 270 nm for the different drugs tested. Drug solutions incubated similarly without cell...

“…The development of cephamycin C, which is known to be resistant to certain betalactamases, raised speculation that this agent 128 might have superior activity against B. fragilis (3,12). In a limited report, Kosmidis et al (10) showed that cefoxitin had greater activity than cephalothin against 10 strains of B. fragilis. The purpose of this study was to examine the in vitro antimicrobial activity of cefoxitin against a miscellany of anaerobic bacteria including B. fragilis and to compare the results with four other cephalosporin antibiotics.…”

mentioning

confidence: 99%

Susceptibility of Anaerobes to Cefoxitin and Other Cephalosporins

Tally

Jacobus²,

Bartlett³

et al. 1975

125

The in vitro susceptibility of 155 strains of anaerobic bacteria to five cephalosporin antibiotics was tested. Cefoxitin was the most active against 33 isolates of Bacteroides fragilis; 82% of the strains were sensitive at 16 jg/ml. At 64 yg/ml cefazolin and cephaloridine were also generally effective. Cephalothin and cephalexin were relatively inactive versus B. fragilis. Cefoxitin, cephaloridine, cefazolin, and cephalothin showed comparable activity against 122 strains of anaerobes other than B. fragilis. More than 90% of the strains were sensitive to each of these antimicrobials at 16 gg/ml. Cephalexin was the least effective cephalosporin against all species tested.