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PubMed1986

Transfer of beta-lactamase-associated cefoxitin resistance in Bacteroides fragilis.

A cefoxitin-resistant Bacteroides fragilis isolate, TAL 4170, which inactivates cefoxitin, was able to transfer beta-lactamase-mediated cefoxitin resistance to a susceptible B. fragilis recipient. Cefoxitin-resistant transconjugants acquired a new beta-lactamase with a pI of 8.1 and were able to inactivate cefoxitin and retransfer cefoxitin resistance. No plasmids were detected in the donor or transconjugants.

Ampicillin↗
PubMed1986

Clinical comparison of piperacillin and cefoxitin in patients with bacteriologically confirmed infections.

The objective of this double-blind study was to compare the efficacy and safety of piperacillin with that of cefoxitin in patients with bacterial infections. Seventy hospitalized patients were treated with intravenous piperacillin (18 g/day) or cefoxitin (12 g/day) for a mean period of 11.5 days. Multiple serious underlying conditions were present in 91% of the patients in both treatment groups. The infection sites were the respiratory, urinary, and gastrointestinal tracts, the skin and skin structures, and the bones. Among the patients with evaluated courses of therapy, 87% (20 of 23) of the patients in the piperacillin-treated group and 90% (19 of 21) of the cefoxitin-treated patients were cured or improved. Multiple sites of infection were present in 6 patients given piperacillin and in 11 patients given cefoxitin. Gram-negative aerobic bacteria were the most frequently isolated organisms (56% of isolates). In each treatment group, 91% of the pathogens were eradicated. Three piperacillin-treated patients (9%) and four cefoxitin-treated patients (11%) had adverse clinical effects related to therapy; most of the effects were moderate in intensity. In conclusion, both piperacillin and cefoxitin were clinically safe and effective antibiotics for the treatment of these patients, most of whom had severe underlying conditions.

Adult↗
PubMed1992

Correlation of various in vitro testing methods with clinical outcomes in patients with Bacteroides fragilis group infections treated with cefoxitin: a retrospective analysis.

There is limited information regarding the correlation of anaerobic susceptibility testing and outcome in the treatment of Bacteroides fragilis infections. We retrospectively analyzed the clinical outcomes of B. fragilis infections in patients treated with cefoxitin; the analysis was blinded for susceptibility results. Isolates of B. fragilis were tested by multiple agar dilution methods, disk elution, and commercial broth microdilution methods. Of 19 patients analyzed, 11 were cured and 8 were treatment failures. No significant differences existed between the groups with respect to age, sex distribution, weight, APACHE II score, dose of cefoxitin, or bacteremia. Failure was associated with a longer cefoxitin dosing interval (P = 0.019), a longer duration of hospitalization (P = 0.038), and decreased duration of cefoxitin treatment (P = 0.05). Four agar dilution systems (brucella plus blood, Wilkins-Chalgren, Wilkins-Chalgren plus blood, brain heart infusion plus blood) and two broth systems (Wilkins-Chalgren microdilution and a commercial system [Micromedia; Beckman, Carlsbad, Calif.]) all demonstrated lower geometric mean MICs for isolates from the group of patients that could be cured. Only the commercial broth microdilution medium (Micromedia) demonstrated a significantly reduced geometric mean MIC (P = 0.056). By using a logistic regression analysis, the shorter cefoxitin dosing interval (P = 0.0004) and the lower geometric mean MIC (P = 0.0088) in the commercial broth microdilution system were shown to be independent predictors of treatment success. These data suggest that the time that the concentration of cefoxitin is over the MIC for B. fragilis may be an important predictor of treatment success.

Adult↗
PubMed1996

In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum-cephalosporins.

Four Klebsiella pneumoniae isolates (LB1, LB2, LB3, and LB4) with increased antimicrobial resistance were obtained from the same patient. The four isolates were indistinguishable in biotype, plasmid content, lipopolysaccharide, and DNA analysis by pulse-field gel electrophoresis. Isolate LB1 made TEM-1 and SHV-1 beta-lactamases. Isolates LB2, LB3, and LB4 produced SHV-5 in addition to TEM-1 and SHV-1. MICs of cefoxitin, ceftazidime, and cefotaxime against LB1 were 4, 1, and 0.06 micrograms/ml, respectively. MICs of ceftazidime against K. pneumoniae LB2, LB3, and LB4 were > 256 micrograms/ml, and those of cefotaxime were 2, 4, and 64 micrograms/ml, respectively. MICs of cefoxitin against K. pneumoniae LB2 and LB3 were 4 micrograms/ml, but that against K. pneumoniae LB4 was 128 micrgrams/ml. K. pneumoniae LB4 could transfer resistance to ceftazidime and cefotaxime, but not that to cefoxitin, to Escherichia coli. Isolate LB4 and cefoxitin-resistant laboratory mutants lacked an outer membrane protein of about 35 kDa whose molecular mass, mode of isolation, resistance to proteases, and reaction with a porin-specific antiserum suggested that it was a porin. MICs of cefoxitin and cefotaxime reverted to 4 and 2 micrograms/ml, respectively, when isolate LB4 was transformed with a gene coding for the K. pneumoniae porin OmpK36. We conclude that the increased resistance to cefoxitin and expanded-spectrum cephalosporins of isolate LB4 was due to loss of a porin channel for antibiotic uptake.

Cefoxitin↗
PubMed1974

Effects of rate of infusion and probenecid on serum levels, renal excretion, and tolerance of intravenous doses of cefoxitin in humans: comparison with cephalothin.

Using a randomized crossover design, 1-g intravenous doses of cephalothin and cefoxitin, a cephalosporinase-resistant cephamycin, were infused into 12 normal adult males over periods of 120, 30, and 3 min, the last with and without prior intravenous infusions of probenecid (1 g). Mean peak serum concentrations of antibiotic activity after cephalothin infusions were 23, 56, 103, and 102 mug/ml, respectively, and after cefoxitin infusions they were 27, 74, 115, and 125 mug/ml, respectively. Probenecid treatment prolonged the terminal serum half-life of cephalothin-like activity from 0.52 to 1.0 h, and of cefoxitin from 0.68 to 1.4 h. In contrast to cephalothin, which was found to be metabolized about 25% to the less active desacetyl form, cefoxitin was metabolized less than 2% to the virtually inactive descarbamyl form, as judged from urinary recoveries. Neither antibiotic displayed detectable organ toxicity. Of 300 recent clinical isolates of gram-negative bacilli other than Pseudomonas spp., 83% were susceptible to cephalothin but 95% were susceptible to cefoxitin. Organisms resistant to cephalothin but susceptible to cefoxitin included strains of Escherichia coli, Proteus vulgaris, Klebsiella spp., Serratia marcescens, Enterobacter spp., and Bacteroides spp.

Adult↗
PubMed2006

Accuracy of cefoxitin disk testing for characterization of oxacillin resistance mediated by penicillin-binding protein 2a in coagulase-negative staphylococci.

The Clinical and Laboratory Standards Institute (CLSI) proposed, beginning in 2004, the use of cefoxitin disks to predict resistance mediated by the mecA gene in all species of coagulase-negative staphylococci (CoNS). The aim of this work was to evaluate the efficiency of the cefoxitin disk and of oxacillin-salt agar screening (MHOX) to characterize the oxacillin resistance mediated by the mecA gene in CoNS. One hundred seven CoNS isolates from different clinical samples were studied. Detection of the mecA gene by PCR was considered the "gold standard." The susceptibility to oxacillin and cefoxitin was detected by the disk diffusion and agar dilution tests, as described by the CLSI. MHOX was also performed with 6 microg/ml of oxacillin and 4% NaCl. The sensitivities of the oxacillin and cefoxitin disks for all CoNS species were 88% and 80%, respectively, whereas the specificities were 63% and 100%, respectively. The sensitivities of the agar dilution test for oxacillin and cefoxitin (for proposed breakpoints of > or =4 microg/ml for resistance and < or =2 microg/ml for susceptibility) were 90% and 85%, respectively, whereas the specificities were 76% and 98%, respectively. MHOX showed a sensitivity of 90% and a specificity of 95% for all CoNS species. Both the MHOX and the cefoxitin disk results indicate that these are appropriate methods for the evaluation of oxacillin resistance mediated by the mecA gene in all CoNS species.

Anti-Bacterial Agents↗
PubMed2002

Evaluation of three techniques for detection of low-level methicillin-resistant Staphylococcus aureus (MRSA): a disk diffusion method with cefoxitin and moxalactam, the Vitek 2 system, and the MRSA-screen latex agglutination test.

Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA). We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMérieux), and the MRSA-screen test (Denka). Detection of the mecA gene by PCR was considered to be the "gold standard." We also determined the sensitivity of the oxacillin disk diffusion method with 5- and 1-microg disks and that of the Oxascreen agar assay with 6 mg of oxacillin liter(-1) for detection of MRSA. We compared the distributions of MICs of oxacillin and cefoxitin by the E-test (AB Biodisk), and those of moxalactam by dilutions in agar, for MRSA and MSSA isolates. The 152 clinical isolates of S. aureus studied were divided into 69 MSSA (mecA-negative) and 83 MRSA (mecA-positive) isolates, including 63 heterogeneous isolates and 26 class 1 isolates (low-level resistance). The cefoxitin and moxalactam disk diffusion tests detected 100% of all the MRSA classes: cefoxitin inhibition zone diameters were <27 mm, and moxalactam inhibition zone diameters were <24 mm. The Vitek 2 system and the MRSA-screen test detected 94 and 97.6% of all MRSA isolates, respectively. The sensitivities of the 5- and 1-microg oxacillin disks were 95.2 and 96.4%, respectively, whereas that of the Oxascreen agar screen assay was 94%. All of the tests except the 1-microg oxacillin disk test were 100% specific. For the class 1 MRSA isolates, the sensitivity of the Vitek 2 test was 92.3%, whereas those of the MRSA-screen test and the disk diffusion method with cefoxitin and moxalactam were 100%. Therefore, the cefoxitin and moxalactam disk diffusion methods were the best-performing tests for routine detection of all classes of MRSA.

Bacterial Proteins↗
PubMed1983

Metronidazole v. cefoxitin in severe appendicitis--a trial to compare a single intraoperative dose of two antibiotics given intravenously.

In severe appendicitis, the effect of a single intravenous dose of metronidazole (500 mg) was compared with cefoxitin (1 g). The antibiotics were given by random allocation once the diagnosis had been established at operation. In the metronidazole group, 5 out of 48 patients developed a wound infection whilst in hospital compared with 13 out of 48 in the cefoxitin group (P = 0.036). However, 57% of wound infections became apparent after the patient went home and the overall infection rates were similar. The mean length of postoperative hospital stay was 5.0 days in the metronidazole group and 6.8 days in the cefoxitin group (P = 0.052), but of those who did develop a wound infection, the length of stay was almost double in the cefoxitin group. Anaerobic organisms were cultured from the wound in 7 out of 15 patients who received cefoxitin but in none of 5 patients in the metronidazole group. Whilst metronidazole only delayed the discharge of pus from the wound, it did seem to reduce the severity of infection. Cefoxitin appeared to be less effective, given as a single intravenous injection at a dose of 1 g.

Adult↗
PubMed1978

Studies of intravenous cefoxitin (MK306).

The pharmacokinetics of cefoxitin, a new cephamycin antibiotic, were studied in six patients who were undergoing total hip replacement, and who were given cefoxitin to provide prophylactic cover at the time of operation. Later, the efficacy of cefoxitin was studied in nine patients with severe acute infections. The mean elimination phase half-life of cefoxitin which was obtained in this study (83 to 87 minutes) was significantly longer than that obtained in other studies. Cefoxitin was also found to be effective in lung and urinary tract infections against sensitive organisms. It was well tolerated, and the only side effect was that of phlebitis in long-term therapy. Cefoxitin may be valuable for prophylactic use in bowel and orthopaedic surgery.

Aged↗
PubMed1991

[A utilization review program of cefoxitin].

A drug utilization review program of cefoxitin was conducted in a 714-bed teaching hospital. Health records of all 43 in-patients who received cefoxitin during the month of November 1987 were reviewed retrospectively. The use of cefoxitin (47 courses) was evaluated on the basis of "appropriate use" criteria developed from the literature and the physician's clinical experience. Of the 47 courses evaluated, cefoxitin was prescribed for prophylaxis in 47%, and its use was considered inappropriate in 86% of these. Overall, 66% of total cefoxitin usage was deemed inappropriate in this hospital. The cost associated with inappropriate use was estimated at $2672 for the period of the study. Corrective measures were then implemented to rectify the identified problems. A second study was conducted 2 years later to assess the impact of the corrective measures. This utilization review program of cefoxitin showed that optimal use of a drug requires not only close collaboration between pharmacists and physicians but a continuous and not a sporadic process of surveillance of the prescription for the drug being studied.

Bacterial Infections↗
PubMed1990

Comparison of single-dose ceftizoxime with multidose cefoxitin chemoprophylaxis for patients undergoing hysterectomy.

A single dose of ceftizoxime was comparable to three perioperative doses of cefoxitin as adjunctive antibiotic chemoprophylaxis against infectious morbidity in women undergoing elective abdominal (60% of patients) or vaginal (40% of patients) hysterectomy. In a double-blind, randomized, prospective, controlled trial, patients were randomized to receive either a single 1-gm dose of ceftizoxime, a newer, broadly active cephalosporin, or three 2-gm doses of cefoxitin intravenously. Twenty-nine women treated with ceftizoxime and 33 women treated with cefoxitin were evaluated. Patient groups were similar for age, other demographic factors, indications for surgery, surgical procedures performed, and selected microbiologic findings. Postoperative infectious morbidity requiring antibiotic treatment was similar among women who received ceftizoxime (27.6%) and those receiving cefoxitin (33%) (P = 0.6). Women receiving ceftizoxime also required a similar number of days of hospitalization (ceftizoxime, 4.7 +/- 1.7 days; cefoxitin, 5.6 +/- 4.5 days; P = 0.3). Both study drugs appeared to be safe and well tolerated. Single-dose ceftizoxime appears to be as efficacious as and more cost-effective than multidose cefoxitin when used as adjunctive chemoprophylaxis in patients at risk for postoperative infection after hysterectomy.

Adult↗
PubMed1987

Cefoxitin interferes with the "Clini-Skreen" column method for urinary 17-hydroxycorticosteroids.

Cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids. The apparent concentration of hormone is increased from three- to 10-fold in samples from patients receiving cefoxitin when the Amberlite XAD-2 "Clini-Skreen" column is used. To determine the mechanism of interference, we reacted aqueous solutions of cefoxitin, cortisol, cortisone, and 11-deoxycortisol with phenylhydrazine; recorded the adsorption spectra; and determined the molar absorptivities and the equilibrium and rate constants. Also, we recorded the absorption spectra of phenylhydrazine with eight other cepha antibiotics and benzylpenicillin. Cortisol, cortisone, 11-deoxycortisol, and cefoxitin react with phenylhydrazine and absorb light with superimposable spectra and absorption maxima of 410 nm. The other antibiotics react with phenylhydrazine but absorbance maxima of the products vary, none being at 410 nm. Cortisol, cortisone, and 11-deoxycortisol react with phenylhydrazine 35-fold faster, have equilibrium constants ninefold greater, and have molar absorptivities 1.6 times that of cefoxitin. Thus, cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids by forming a chromophore with the same absorbance maximum and with a molar absorptivity similar to cortisol, but much more slowly.

17-Hydroxycorticosteroids↗
PubMed1986

Pharmacokinetics and body fluid and endometrial concentrations of cefoxitin in mares.

Four healthy adult mares were each given a single injection of sodium cefoxitin (20 mg/kg of body weight, IV), and serum cefoxitin concentrations were measured serially during a 6-hour period. The mean elimination rate constant was 1.08/hour and the elimination half-life was 0.82 hour. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.12 L/kg and 259 ml/hr/kg, respectively. Each mare and 2 additional mares were then given 4 consecutive IM injections of sodium cefoxitin (400 mg/ml) at a dosage of 20 mg/kg. Cefoxitin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 23.1 micrograms/ml 30 minutes after the 2nd injection. The highest mean synovial concentration was 11.4 micrograms/ml 1 hour after the 4th injection. The highest mean peritoneal concentration was 10.4 micrograms/ml 2 hours after the 4th injection. The highest mean endometrial concentration was 4.5 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 11,645 micrograms/ml. Cefoxitin did not readily penetrate the CSF. Bioavailability of cefoxitin given IM was 65% to 89% (mean +/- SEM = 77% +/- 5.9%). One of the 6 mares developed acute laminitis during the IM experiment.

Animals↗
PubMed1979

Cefoxitin: single-agent treatment of mixed aerobic-anaerobic pelvic infections.

Cefoxitin (mefoxin), a new semisynthetic cephamycin antibiotic, resistant to degradation by beta-lactamase enzymes produced by bacteria. In vitro, cefoxitin is active against virtually all clinically important gram-negative facultative bacteria other than Pseudomonas and Enterobacter spp., gram-positive aerobic bacteria other than the enterococcus, and clinically important anaerobic organisms, including Bacteroides fragilis. This broad antibacterial spectrum suggested that cefoxitin might be an effective single antibiotic agent for the treatment of mixed aerobic-anaerobic infections in obstetric and gynecologic patients. In this investigation, the efficacy and safety of cefoxitin was evaluated in 109 patients--68 with salpingitis, 25 with endomyometritis, 9 with pelvic cellulitis, and 7 with pelvic abscesses. An average of 2.5 bacteria were isolated from each patient. Aerobic bacteria alone was isolated in 38% of patients, anaerobic bacteria alone in 25%, and a combination of aerobic and anaerobic bacteria was isolated in 37% of patients. Overall, 100 of 109 (92%) infections responded to treatment with cefoxitin alone. The major cause of treatment failure was the presence of abscesses requiring surgical drainage. In addition to being an effective single agent for the management of pelvic infections, cefoxitin proved to be safe and well tolerated by patients.

Abscess↗
PubMed1983

Prophylactic cefoxitin in cesarean section.

The effectiveness of prophylactic cefoxitin in preventing postcesarean section infection was studied in a high risk population. One hundred women were evaluated, and on a random double-blind basis 50 received placebo and 50 received cefoxitin. There were three doses of drug given intravenously, either placebo or 1 gram of cefoxitin at the time of cord clamping and again four and eight hours later. Those receiving cefoxitin had significantly less postoperative infections, fewer had bacteremia and there was less postoperative fever as measured by the fever index. The patient with the most protracted infection in this study received cefoxitin. Problems with the use of systemic antibiotic prophylaxis in preventing postcesarean section infection are discussed. Cefoxitin is an effective agent to use in patients undergoing cesarean section who are at high risk for infection.

Adult↗
PubMed1983

Evaluation of efficacy of cefoxitin in the prevention of abdominal trauma infections.

Recent studies showed high populations of both aerobes and anaerobes in penetrating abdominal trauma infections. Combined aminoglycoside-clindamycin therapy has resulted in infection rates of 7 to 10 per cent. However, high side-effect incidences of nephrotoxicity and ototoxicity have been attributed to the aminoglycosides. Cefoxitin is reportedly free of these side effects. In our study, 62 penetrating abdominal trauma patients requiring laparotomy were treated with cefoxitin pre- and postoperatively. The majority of the injuries, 75.8 per cent, involved small bowel and large bowel. Infections occurred in four patients of the total 62 (6.5%). Two side effects, a fever and a rash, subsided immediately after discontinuing cefoxitin; no ototoxicity or nephrotoxicity occurred. The safety and efficacy of cefoxitin alone versus aminoglycoside-clindamycin combination therapy was statistically compared in intestinal injuries only among two historical controls and our subgroup. Our infectious rate, 8.5 per cent, was comparable to 7.4 per cent and 10.4 per cent of the historical controls. We concluded that pre- and postoperative use of cefoxitin alone is as effective in the prevention of penetrating abdominal trauma infections as combined aminoglycoside-clindamycin therapy. Experience to date suggests that the use of a beta-lactam antibiotic such as cefoxitin may allow the physician to avoid the more serious side effects associated with the use of aminoglycosides in these patients.

Abdominal Injuries↗
PubMed1978

[Microbiological evaluation of cefoxitin, a new beta-lactamase resistant cephamycin antibiotic, compared to cephalothin, cephaloridine and cefazolin].

Cefoxitin (Mefoxitin), Cephaloridin, Cephalothin and Cefazolin were tested in vitro against 380 clinical isolates of Staph. aureus and Enterobacteriaceae using the tube dilution procedure. Of the gramnegative microorganisms a selection of 150 strains was examined regarding susceptibility to the antibiotic combinations cefoxitin/gentamicin and cefoxitin/sisomicin in comparison to cephalothin/gentamicin and cephalothin/sisomicin. Cefoxitin has a broad antimicrobial spectrum and a high beta-lactamase-resistance. Cefoxitin was more active than the other antibiotics tested against E. coli, Klebsiella, Serratia, Enterobacter, indole-negative and -positive Proteus species. The high effectiveness of cefoxitin against anaerobic bacteria such as Bacteroides fragilis and Clostridium perfringens is discussed. Cefoxitin has an excellent bactericidal potency. Among the combinations tested cefoxitin/sisomicin was most active and obtained synergistic effects in most species. The resistance rate of cefoxitin of 8.7% was reduced to 0.7% with cefoxitin/sisomicin.

Cefazolin↗
PubMedDate not supplied

Intraoperative serum concentrations of cefazolin and cefoxitin administered preoperatively at different times.

The effect of administration time on the serum concentrations of cefazolin and cefoxitin achieved during surgery was studied. Patients about to undergo elective surgery were randomly selected to receive one of four antibiotic prophylaxis regimens. Two of the regimens consisted of cefazolin 20 mg/kg i.v. (as the sodium salt) administered either "on call" to the operating room or with anesthesia in the operating room. The other two regimens were identical except that cefoxitin 30 mg/kg i.v. (as the sodium salt) was substituted for cefazolin. Intraoperative blood samples for analysis of serum concentrations were obtained at the time of surgical incision, one hour after incision, and at wound closure. Forty patients completed the study (10 patients received each treatment). Mean projected cefazolin concentrations at the time of incision and at wound closure for both two-hour and three-hour operations were significantly higher after administration with anesthesia than after "on-call" administration. For cefoxitin, differences in projected concentrations for "on-call" administration versus administration with anesthesia were significant at the time of incision and at wound closure in a two-hour operation. At times corresponding to initial incision, projected free-cefoxitin concentrations were higher than those of cefazolin; however, projected free-cefazolin concentrations were higher than free-cefoxitin concentrations at wound closure for two-hour and three-hour operations. To ensure that antibiotic is present in serum throughout a two- or three-hour surgical procedure, cefoxitin should probably be administered at the induction of anesthesia. Cefazolin administered "on call" appears to be acceptable for maintaining serum concentrations throughout surgery of this duration.

Adolescent↗