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PubMedDate not supplied

Inhibitory and bactericidal activity of selected beta-lactam agents alone and in combination with beta-lactamase inhibitors compared with that of cefoxitin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates of the Bacteroides fragilis group.

The inhibitory activity of five beta-lactam agents, alone and in combination with a beta-lactamase inhibitor, was compared with that of cefoxitin and metronidazole against 300 beta-lactamase producing Bacteroides fragilis group isolates. Each of the beta-lactamase inhibitors significantly potentiated the activity of the respective beta-lactam. In the presence of clavulanate, the MIC90 (minimum inhibitory concentration) values of amoxicillin and ticarcillin were reduced 64-fold and 32-fold, respectively. Similarly, sulbactam enhanced the activity of ampicillin and cefoperazone 16-fold and 8-fold, respectively, whereas tazobactam potentiated the activity of piperacillin 16-fold. Few strains were resistant to the beta-lactam-beta-lactamase inhibitor combinations and were comprised of strains of B. fragilis, B. thetaiotamicron, and B. distasonis. Of the strains, 7% were resistant to cefoxitin, and none to metronidazole. Using time-kill kinetic studies, the bactericidal activity of the various beta-lactam agents, with and without beta-lactamase inhibitors, was determined and compared with that of cefoxitin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates of the B. fragilis group. Overall, metronidazole was the most bactericidal agent with all isolates being killed with less than or equal to 4 micrograms/ml at 24 hr. Ampicillin-sulbactam was the next most bactericidal agent with all isolates being killed with less than or equal to 16/8 micrograms/ml of ampicillin-sulbactam at 24 hr. Amoxicillin-clavulanate and cefoperazone-sulbactam had bactericidal activity similar to that of ampicillin-sulbactam. Piperacillin-tazobactam and ticarcillin-clavulanate were bactericidal at higher concentrations with all isolates killed with 64 micrograms/ml of piperacillin and 128 micrograms/ml of ticarcillin combined with their respective beta-lactamase inhibitors. None of the beta-lactam agents alone was able to kill more than 19 of the 26 isolates. We conclude that beta-lactam agents combined with beta-lactamase inhibitors have both inhibitory and bactericidal activity against cefoxitin-resistant members of the B. fragilis group provided that the concentrations achieved for these combinations are at the upper limits for maximum recommended dosing. Although isolates of the B. fragilis group have been reported to produce unusual beta-lactamases that are refractory to beta-lactamase inhibitors, none of the cefoxitin-resistant isolates tested in this study were resistant to the beta-lactam-beta-lactamase inhibitor combinations.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparison of the bactericidal activity of clindamycin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates of the Bacteroides fragilis group.

Time-kill kinetic methodology was used to evaluate the bactericidal activity of cefoxitin, cefotetan, clindamycin, and metronidizole against cefoxitin-susceptible and cefoxitin-resistant isolates of the Bacteroides fragilis group. Overall, metronidazole was the most bactericidal agent, with all isolates being killed with less than or equal to 4 micrograms/ml at 24 hr. Clindamycin was the next most bactericidal agent, with 20 of 26 isolates being killed with less than 16 micrograms/ml. Six isolates with clindamycin MICs greater than or equal to 64 micrograms/ml were not killed at 24 hr, with concentrations as high as 256 micrograms/ml. Cefoxitin and cefotetan were the least bactericidal agents tested. Seven isolates with MICs of greater than or equal to 64 micrograms/ml to each agent demonstrated a lack of killing at 24 hr, with concentrations of the respective agent as high as 256 micrograms/ml. At concentrations with either agent of 32 micrograms/ml, the remaining 19 isolates were killed at 24 hr. Of the six B. fragilis isolates resistant to clindamycin, four were also resistant to both cefoxitin and cefotetan. We conclude that in hospitals with cefoxitin-resistant B. fragilis group isolates, metronidazole would provide appropriate therapy.

Bacteroides↗
PubMed1991

Evaluation of cycloserine-cefoxitin-fructose agar and cycloserine-cefoxitin-fructose broth for recovery of Clostridium difficile from environmental sites.

Cycloserine-cefoxitin-fructose agar (CCFA) and cycloserine-cefoxitin-fructose broth (CCFB) containing either 500 or 250 micrograms of cycloserine per ml were compared for efficacy in the isolation of Clostridium difficile from hospital ward environmental sites. A RODAC imprint technique was used to inoculate prereduced CCFA. Moistened swabs were used to inoculate prereduced CCFB from environmental sites immediately adjacent to the RODAC sample sites. CCFA (6% positive) was significantly more sensitive than CCFB (3% positive; P less than 0.005), regardless of the cycloserine concentration. When the CCFA cycloserine concentration was decreased from 500 to 250 micrograms/ml, the overall rate of positive cultures rose from 4 to 17%. Medium containing 500 micrograms of cycloserine per ml may be too inhibitory to isolate many moderately sensitive strains of C. difficile from environmental sites. Regardless of the cycloserine concentration, the CCFA RODAC imprint technique is superior to the CCFB method.

Agar↗
PubMed1978

Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli.

The affinities of cefoxitin, a cephamycin antibiotic, to penicillin-binding proteins of Escherichia coli were reexamined using a recently developed method for separating penicillin-binding proteins. The inhibitions by this antibiotic of four measurable penicillin-sensitive enzymatic reactions, the reactions of D-alanine carboxypeptidases IA and IB, cross-bridge formation and concomitant release of D-alanine, were also measured. An approximate correlation was found between the affinities of cefoxitin to the penicillin-binding proteins responsible for these reactions and its rates of inhibition of the respective penicillin-sensitive reactions.

Bacterial Proteins↗
PubMed1977

Antimicrobial evaluation of cefoxitin: a new semisynthetic cephamycin. Comparative studies with cefazolin and cefalotin.

Antimicrobial activity of 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (cefoxitin), a new semisynthetic cephamycin antibiotic, was studied in comparison with that of cefazolin and cefalotin. Cefoxitin exhibited antibacterial activity against both gramnegative and gram-positive bacteria, and its action was bactericidal. Against gram-negative bacteria, cefoxitin was highly active as well as cefazolin, and more active than cefalotin. Especially, cefoxitin was highly active not only against strains of clinical isolates of indole-positive Proteus and S. marcescens but also against those of E. coli and P. mirabilis which were resistant to cefazolin and/or cefalotin, respectively. In addition, cefoxitin was effective against the strains resistant to beta-lactam antibiotics including cefazolin and cefalotin. Cefoxitin was hardly active against the strains of E. cloacae and P. aeruginosa, similar to cefazolin and cefalotin. Against gram-postive bacteria, cefoxitin was less active than cefazolin and cefalotin. In protection tests in mice, cefoxitin and cefazolin were more effective against infection with E. coli than cefalotin. Furthermore, cefoxitin was more active against infections with S. marcescens and P. morgani than the other antibiotics. Cefoxitin, like cefalotin, was less effective against infection with S. aureus than cefazolin. Cefoxitin was highly resistant to hydrolysis by beta-lactamases derived from the organisms insusceptible to the antibiotic. This fact revealed that the resistance of the organisms to cefoxitin may be in part due to factors other than beta-lactamase inactivation.

Animals↗
PubMed1988

Comparative study of cefotetan and cefoxitin in the treatment of intra-abdominal infections.

One hundred eighty-eight patients were enrolled in a multicenter, randomized clinical trial to compare the safety and effectiveness of 1 to 2 gm cefotetan every 12 hours with those of 1 to 2 gm cefoxitin every 6 hours in patients with intra-abdominal infections. Most of the infections were community acquired, were associated with gastrointestinal tract perforation, and were caused by both anaerobic and aerobic bacteria. The median duration of therapy was 6 days for each group. The clinical response rate for the 95 evaluable patients in the cefotetan group was 98%, and that for the 43 evaluable patients in the cefoxitin group was 95%. Bacteriologically, 97% of the 58 evaluable patients in the cefotetan group and 89% of the 27 evaluable patients in the cefoxitin group had a satisfactory or presumed satisfactory response; two patients in the cefotetan group and three in the cefoxitin group were considered bacteriologic failures. Cefotetan was as effective as cefoxitin in eradicating Bacteroides fragilis and other species of Bacteroides, Clostridium sp., and gram-negative bacilli. The incidence of treatment-related adverse reactions for cefotetan (27%) was not statistically different from that for cefoxitin (17%). No clinically significant differences were detected between the treatment groups in changes in the results of clinical laboratory tests performed before and after treatment; a decrease in hematocrit among the cefotetan group was statistically greater (p = 0.04) than that for the cefoxitin group, and a decrease in serum creatinine level for the cefoxitin group was greater than that for the cefotetan group (p = 0.02). Cefotetan may represent an effective, safe, and cost-saving alternative to cefoxitin for the prompt treatment of community-acquired intra-abdominal infections.

Abdomen↗
PubMed1989

Pharmacokinetics and pharmacodynamics of total and unbound cefoxitin and cefotetan in healthy volunteers.

Cefotetan is a semisynthetic cephalosporin with a broad spectrum of Gram-negative and anaerobic activity. We compared the pharmacokinetics and serum inhibitory activity of 2 g doses of cefotetan and cefoxitin in six healthy volunteers. The half-life of cefotetan (176 min) was significantly longer than that of cefoxitin (49 min). Despite higher protein binding (85% versus 50%), free cefotetan serum concentrations 12 h post dose (1.6 mg/l) were higher than free cefoxitin serum concentrations 6 h post dose (0.32 mg/l). Total and free serum inhibitory titres for Escherichia coli were greater than 1:8 for 12 h post dose for cefotetan, but only 1 h post dose for cefoxitin. Against Bacteroides fragilis, neither cefoxitin nor cefotetan exhibited free serum inhibitory titres greater than 1:8 at the end of their respective dosing intervals. However, cefotetan titres were equivalent or superior to those of cefoxitin over the entire 6 or 12 h dosing interval. Despite relatively high protein binding, cefotetan demonstrates comparable or superior activity 12 h after dosing to cefoxitin 6 h after dosing. More studies comparing the clinical outcome of cefoxitin and cefotetan are needed but our results support the clinical recommendations that cefoxitin should be given every 6 h, and cefotetan every 12 h.

Adult↗
PubMed1987

Clinical importance of cefoxitin-resistant Bacteroides fragilis isolates.

Resistance to cefoxitin among species of the Bacteroides fragilis group of organisms has remained low (8%-10%) in a multicenter nationwide survey. However, a statistically significant increase in the percentage of B. fragilis group organisms resistant to cefoxitin was found at Tufts-New England Medical Center from 1981 to 1982. Non fragilis species accounted for most of the resistance. The presence of cefoxitin resistance in B. fragilis isolates correlated with resistance to other antibiotics. The presence of cefoxitin-resistant B. fragilis group organisms also correlated with the presence of other cefoxitin-resistant bacteria. No difference could be detected in therapeutic outcome of patients with cefoxitin-sensitive or cefoxitin-resistant B. fragilis group organisms, regardless of treatment with cefoxitin or other antibiotics.

Age Factors↗
PubMed1986

Inactivation of cefoxitin and moxalactam by Bacteroides bivius beta-lactamase.

Moxalactam and cefoxitin are known for their high stability against Bacteroides beta-lactamases. We investigated the beta-lactamase activity of crude extracts obtained from three strains of Bacteroides bivius and two strains of Bacteroides fragilis against cefoxitin and moxalactam. In a spectrophotometric antibiotic assay with a 24-h incubation period, B. bivius extracts decreased the initial concentration (10 micrograms/ml) of moxalactam and cefoxitin by 60%, whereas B. fragilis extracts had no effect. In a microbiological assay, when B. bivius or B. fragilis extracts were added to cephalothin (10 micrograms/ml) or cefamandole (4 micrograms/ml), we observed complete disappearance of the inhibitory zones against the indicator strain (Clostridium perfringens ATCC 13124). Only the B. bivius extracts were able to decrease the inhibitory activity (from 10 to 100%) of cefoxitin and moxalactam (each at 10 micrograms/ml). Prior addition of clavulanic acid to crude extracts prevented the losses of antibacterial activity. Furthermore, the inhibition of the beta-lactamase hydrolysis of nitrocefin by cefoxitin or moxalactam was prevented by a 12-h preincubation of the beta-lactam with the B. bivius extracts but not with the B. fragilis extracts. Finally, with the B. bivius strain producing the most beta-lactamase, we showed an effect of inoculum size on the MICs of cefoperazone, cefoxitin, and moxalactam with a broth dilution technique. Increasing the inoculum size with the B. fragilis strains had no effect on the MISs of cefoxitin and moxalactam. These results indicate a slow and clavulanate-sensitive beta-lactamase activity of B. bivius extracts against cefoxitin and moxalactam.

Bacteroides↗
PubMedDate not supplied

Comparative activity of cefoxitin, ampicillin/sulbactam, and imipenem against clinical isolates of Escherichia coli and Klebsiella pneumoniae.

The in vitro activities of cefoxitin, ampicillin/sulbactam, and imipenem were determined by the standard twofold agar dilution method against 62 strains of Escherichia coli and 40 strains of Klebsiella pneumoniae isolated from patients in intensive care units. Judging from the concentrations required to inhibit at least 90% of the test isolates, imipenem (MIC90 less than or equal to 0.125 micrograms/ml) was markedly more active than cefoxitin (MIC90 = 4 micrograms/ml) and ampicillin/sulbactam (MIC90 = 32 micrograms/ml) against both bacterial genera. Cefoxitin, therefore, was more active than ampicillin/sulbactam against these organisms. Breakpoints specified in the prescribing information are less than or equal to 4 micrograms/ml for imipenem, less than or equal to 16 micrograms/ml for cefoxitin, and less than or equal to 8 micrograms/ml for ampicillin/sulbactam. At these breakpoints all organisms were susceptible to imipenem and cefoxitin, while 73% of E coli and 78% of K pneumoniae were susceptible to ampicillin/sulbactam. At recommended susceptible MIC breakpoints of the National Committee for Clinical Laboratory Standards (less than or equal to 4 micrograms/ml for imipenem, less than or equal to 8 micrograms/ml for cefoxitin, and less than or equal to 4 micrograms/ml for ampicillin/sulbactam) all the isolates tested were susceptible to imipenem, while 98% and 73% of the E coli isolates were susceptible to cefoxitin and ampicillin/sulbactam, respectively, and 100% and 78% of the K pneumoniae isolates were susceptible to cefoxitin and ampicillin/sulbactam, respectively. Approximately 14% of E coli and 17% of K pneumoniae isolates were resistant to ampicillin/sulbactam (MIC greater than or equal to 32/16 micrograms/ml).

Ampicillin↗
PubMed1979

Cefoxitin sodium compatibility with intravenous infusions and additives.

The compatibility and stability of cefoxitin sodium in solution with a series of frequently used intravenous infusion fluids and injectable additives were studied. Cefoxitin sodium's stability in various solutions was measured by ultraviolet spectrophotometry, iodometry, thin-layer chromatography, high-pressure liquid chromatography, ion-exchange chromatography and microbiological assay. Cefoxitin sodium was shown to maintain 90% of its initial concentration in aqueous solution for 40 hours at room temperature (25 C) and about 30 days at 5 C. The stability of cefoxitin sodium in common i.v. infusion fluids was independent of the concentrations (1 mg/ml to 400 mg/ml) and containers used, and was retained after 30 weeks storage at -20 C. Similar stability patterns were demonstrated for cefoxitin sodium in protein hydrolysate solutions and multivitamin formulations. Cefoxitin sodium was chemically and visually compatible with amikacin sulfate, gentamicin sulfate, kanamycin sulfate and tobramycin sulfate when admixed with normal saline or 5% dextrose in water injections. Cefoxitin sodium (397 mg/ml) in 0.5% lidocaine hydrochloride was stable after 26 weeks of storage at -20 C. Sodium cefoxitin is compatible with a wide variety of commonly used infusion solutions. Its stability is independent of concentration or pH within the ranges studied, and of types of common containers.

Aminoglycosides↗
PubMed1973

Cefoxitin, a new semi-synthetic cephamycin: an in-vitro and in-vivo comparison with cephalothin.

The activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indole-producing Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by beta-lactamases produced by Gram-negative organisms. Against Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood levels.Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.

Adolescent↗
PubMed1988

Single-dose cefotetan versus multiple-dose cefoxitin as prophylaxis in colorectal surgery.

The safety and effectiveness of a single 2 g preoperative dose of cefotetan to reduce postoperative infectious complications after colorectal surgery was compared with multiple 2 g perioperative doses of cefoxitin in 289 patients enrolled in a multicenter trial; of the 239 evaluable patients, 164 received cefotetan and 75, cefoxitin. No statistically significant difference was detected in the successful clinical response rates for cefotetan and cefoxitin (88 percent and 92 percent, respectively). The difference in median increase in oral body temperature before and after the study (2.5 degrees F for cefotetan and 2 degrees F for cefoxitin) was statistically but not clinically significant (p = 0.03). Although nearly four times as many cefotetan patients as cefoxitin patients had surgery lasting 4 hours or more, the satisfactory bacteriologic response rates for cefotetan and cefoxitin were similar (88 percent and 93 percent, respectively). Nonobese patients and patients whose surgical procedures lasted less than 4 hours treated with either drug had significantly higher success rates (p less than 0.01). The incidence of major wound infection was approximately 8 percent for both treatment groups. Mean concentrations of cefotetan in plasma, specimens of colon, and subcutaneous fat were 128 +/- 61.8 micrograms/ml, 57.2 +/- 40.4 micrograms/g, and 26.8 +/- 19.4 micrograms/g, respectively. The incidence of adverse reactions was 12 percent for each group, and no reaction was considered treatment-related, including changes in results of clinical laboratory tests. A single 2 g preoperative dose of cefotetan was as safe and effective as multiple doses of cefoxitin in the reduction of postoperative wound infections after colorectal surgery.

Adult↗
PubMed1988

Multicenter open trial of cefotetan and cefoxitin in elective biliary surgery.

The present study was performed in two phases. In phase I, 112 patients were randomized to either 2 g cefotetan as a single prophylactic dose or 2 g cefoxitin every 6 hours for a maximum of 4 doses; phase II included 148 patients who were randomized to either 1 g cefotetan as a single dose or cefoxitin dosed as in phase I. The randomization was 2:1 cefotetan to cefoxitin in both phases. Nonevaluability rates were 10 percent for the cefotetan patients and 22 percent for the cefoxitin patients, the majority being due to dosing errors. Demographic characteristics demonstrated 88 percent to be female, 81 percent to be less than 65 years of age, and the average weight to be 165 lb. There were no differences in these characteristics among the groups. Common duct exploration was performed in 6 percent of the 2 g cefotetan patients, 9 percent in the 1 g cefotetan patients, and 13 percent in the 2 g cefoxitin patients. There were five clinical failures of prophylaxis: one wound infection in the 2 g cefotetan patients, one wound infection and one drain tract infection in the 1 g cefotetan patients, and one wound infection and one case of cholangitis in the 2 g cefoxitin patients. The clinical success rates were 98 percent in the 2 g cefotetan patients, 98 percent in the 1 g cefotetan patients, and 97 percent in the 2 g cefoxitin patients.

Aged↗
PubMed1988

A multicenter comparative study of cefotetan once daily and cefoxitin thrice daily for the treatment of infections of the skin and superficial soft tissue.

To compare the effectiveness of cefotetan administered at 2 g once a day with cefoxitin at 1 or 2 g three times a day in the treatment of hospitalized patients with skin and superficial soft tissue infections, 194 patients from eight centers were enrolled in an open, randomized trial. Most of the 104 evaluable patients in the cefotetan group and 50 in the cefoxitin group were young men with community-acquired, moderate or severe cellulitis, or abscesses of the upper and lower extremities caused by Staphylococcus aureus, Streptococcus species, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and other species of bacteroides, peptococcus species, and peptostreptococcus species. The mean duration of treatment was 7.5 days for cefotetan and 7.1 days for cefoxitin. A successful clinical response was achieved in 97 percent of the cefotetan patients and in 94 percent of the cefoxitin patients. Of the 88 and 39 bacteriologically evaluable patients in the cefotetan and cefoxitin groups, respectively, a satisfactory bacteriologic response occurred in 96 percent and 87 percent of the patients. No clinically significant changes in clinical laboratory determinations were noted. The incidence of adverse reactions in the cefotetan group (17 percent) was significantly different from that for the cefoxitin group (6 percent) (p less than 0.05); however, the incidence of treatment-related reactions was not significant and the events were mild. Discontinuation of therapy was necessary only in two patients in whom allergic-type reactions developed. A once-daily regimen of cefotetan was as effective as thrice-daily cefoxitin in this study in the treatment of primarily polymicrobial, moderate, or severe infections of the skin and superficial soft tissue.

Abscess↗
PubMed1979

Cefoxitin as a single-dose treatment for urethritis caused by penicillinase-producing Neisseria gonorrhoeae.

Gonococci that resist standard penicillin regimens by production of a penicillinase are now well established in certain areas of the world. Because cefoxitin, a semisynthetic cephamycin, resists gonococcal penicillinase in vitro, we compared procaine penicillin G and cefoxitin in treatment of gonorrhea in an area where 40 per cent of isolates produce penicillinase. One hundred and seven men with culture-proved gonococcal urethritis were given a single dose of either procaine penicillin G, 4.8 million U, or cefoxitin, 2 g, intramuscularly. Both groups took 1 g of probenecid orally; cefoxitin was given with lidocaine to reduce pain at the injection site. In men infected with penicillinase-negative gonococci, both cefoxitin and penicillin were highly effective. Penicillin failed in 77 per cent of men with penicillinase-positive strains, whereas cefoxitin was completely successful. Cefoxitin is an effective alternative to spectinomycin for single-session therapy of urethritis caused by penicillinase-producing Neisseria gonorrhoeae.

Cefoxitin↗