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The biochemical bonding of cefoxitin to a microporous polytetrafluoroethylene surface.

Cefoxitin was bound to a microporous polytetrafluoroethylene (PTFE) surface with tridodecylmethylammonium chloride (TDMAC). Bactericidal concentrations of cefoxitin were achieved with very small doses of the antibiotic. Elution of cefoxitin from microporous PTFE occurs by two concurrent first-order processes, each occurring at a different rate constant. Bound cefoxitin inhibits the growth of Staphylococcus aureus in a bioassay. Finally, cefoxitin can be adsorbed to TDMAC-treated microporous PTFE in vivo when the antibiotic is administered locally or intravenously. The application of antibiotic bonding to the prevention of vascular prosthetic infections is discussed.

Animals↗

Six-year retrospective survey of the resistance of Bacteroides fragilis group species to clindamycin and cefoxitin.

Two hundred and forty-six strains of the Bacteroides fragilis group, all clinical isolates, collected at the Wadsworth Veterans Administration Medical Center from 1977 to 1982, were tested for susceptibility to clindamycin and cefoxitin. There was no significant change in resistance to either clindamycin or cefoxitin over the time period tested for any individual species, nor for the B. fragilis group in toto. Striking differences in susceptibility to the two drugs were seen among species of the B. fragilis group. B. fragilis displayed resistance to cefoxitin (32 micrograms/ml) and clindamycin (8 micrograms/ml) of 0.0% and 0.8%, respectively, whereas B. thetaiotaomicron showed resistances of 12.7% to cefoxitin (32 micrograms/ml) and 9% to clindamycin (8 micrograms/ml). B. thetaiotaomicron, B. distasonis, and B. ovatus are distinctly more resistant to cefoxitin than B. fragilis and B. vulgatus. Similarly B. thetaiotaomicron and B. distasonis are much more resistant to clindamycin than are the other B. fragilis group species. It is apparent that determination of species within the B. fragilis group is important in evaluating a potential therapeutic regimen.

Bacteroides fragilis↗

Comparative antimicrobial activity of aminothiazolyl methoxyimino cephalosporins against anaerobic bacteria, including 100 cefoxitin-resistant isolates.

Three aminothiazolyl methoxyimino cephalosporins (ceftizoxime, ceftriaxone, and cefotaxime with and without its metabolite) were tested against 500 strains of anaerobic bacteria using the NCCLS reference agar dilution procedure. Eighty-seven percent of all strains tested were from the Bacteroides fragilis group. When tested against a collection of 100 cefoxitin-resistant isolates, ceftizoxime and the cefotaxime/desacetyl-cefotaxime combination were the most active in vitro, inhibiting 32-38% of strains. Ceftriaxone inhibited the greatest number (87%) of cefoxitin-susceptible anaerobes at less than or equal to 32 micrograms/ml. A regional variation in the activity of these drugs was confirmed when an additional 300 isolates were examined from three medical centers. Cefotaxime, ceftizoxime, and ceftriaxone were essentially equal in overall antimicrobial activity, although each drug was judged the best at one of the three locations. Cefoxitin resistance (MIC greater than or equal to 32 micrograms/ml) was consistent among the institutions at a 25% incidence for all organisms tested, and 28% cefoxitin resistance among the B. fragilis group strains. Cefoxitin resistance was not determined to be associated with a beta-lactamase mechanism, but ceftriaxone and other aminothiazolyl cephems were hydrolyzed, thus elevating their MICs. Regional variation in anaerobic organism susceptibility to cephamycins and cephalosporins in company with the variable beta-lactam resistance mechanisms seems to require periodic, epidemiologic monitoring of in vitro drug activity by appropriate methods to assure continued antimicrobial efficacy.

Bacteria, Anaerobic↗

Cefmenoxime versus cefoxitin in the treatment of serious bacterial infections.

A comparative study was conducted using cefmenoxime, a new extended spectrum cephalosporin, versus cefoxitin. Entry into the study was based on a computer-generated randomization (two cefmenoxime to one cefoxitin). An intravenous dose of cefmenoxime (0.5 to 1 g every six hours) or cefoxitin (1 to 2 g every six hours) was administered to patients suspected of having serious bacterial infections. Six patients had urinary tract infections. Four who received cefmenoxime, including two with positive blood cultures, had eradication of bacteremia. One of the two who received cefoxitin had significant bacteriuria, and the urine was clear after treatment. Twenty-four patients were treated for lower respiratory tract infections. All 15 patients who received cefmenoxime had clinical and bacteriologic cures. Two of the nine patients who received cefoxitin continued to have the pathogens at the end of the treatment period. Both patients had a neoplasm of the lung. All 11 patients who had soft tissue infections (nine of whom received cefmenoxime) responded well. Both antibiotics were well tolerated.

Bacterial Infections↗

Results of a randomized, multicenter, comparative trial of a single dose of cefotetan versus multiple doses of cefoxitin as prophylaxis in cesarean section.

In a multicenter, open, randomized, comparative trial, 308 women undergoing cesarean section were given a single 1 gm dose of cefotetan or three 2 gm doses of cefoxitin after cord clamping to reduce the incidence of postoperative infectious morbidity. Of the 286 evaluable patients, 195 received cefotetan and 91 received cefoxitin. Most patients were in active labor and one third had ruptured membranes. Microorganisms cultured from the endocervix or intraoperatively from the endometrium or abdominal wall operative sites were comparable for the two groups. In this multicenter study, the difference between the percentage of patients receiving cefotetan who did not develop clinical signs and symptoms of infection (93%) and the percentage of patients receiving cefoxitin (85%) considered clinical successes was statistically significant (p = 0.02, chi 2). The bacteriologic response rate for patients taking cefotetan was also significantly higher than that for patients taking cefoxitin (93% versus 85%, p = 0.03). Isolates recovered from the endocervix, endometrium, or operative site were comparable for the two groups. Both drugs were well tolerated. In this evaluation, cefotetan administered in a single dose of 1 gm was more effective as a prophylactic agent than multiple 2 gm doses of cefoxitin in the reduction of infectious morbidity in this large series of patients undergoing cesarean section.

Adolescent↗

Comparison of cefotetan and cefoxitin prophylaxis for abdominal and vaginal hysterectomy.

The safety and efficacy of parenteral prophylaxis with either cefotetan or cefoxitin were evaluated in a prospective, randomized study of 355 subjects undergoing abdominal or vaginal hysterectomy. Each subject received either a single 1 gm dose of cefotetan intravenously 30 to 60 minutes before operation or three 2 gm doses of cefoxitin, the first 30 to 60 minutes before operation and subsequent doses 6 and 12 hours later. Prophylaxis was successful in 69 of 70 (98.6%) receiving cefotetan and 32 of 33 (97.0%) receiving cefoxitin who underwent vaginal hysterectomy. Prophylaxis was successful in 160 of 169 (94.7%) receiving cefotetan and in 79 of 83 (95.2%) receiving cefoxitin who underwent abdominal hysterectomy. Both drugs were well tolerated and without serious side effects or complications. On the basis of these findings, we conclude that a single 1 gm dose of cefotetan given before operation is as safe and effective as a multiple-dosing regimen of cefoxitin in subjects undergoing vaginal hysterectomy and in those undergoing abdominal hysterectomy at institutions where prophylaxis is indicated.

Abdomen↗

Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and cefoxitin plus doxycycline.

Acute pelvic inflammatory disease remains the major medical and economic consequence of sexually transmitted diseases among young women. The polymicrobial origins of pelvic inflammatory disease have been well documented and the major organisms recovered from the upper genital tract in patients with pelvic inflammatory disease include Chlamydia trachomatis, Neisseria gonorrhoeae, and mixed anaerobic and aerobic bacteria. This study was undertaken to compare the efficacy and safety of cefotetan plus doxycycline with that of cefoxitin plus doxycycline in the treatment of hospitalized patients with acute pelvic inflammatory disease. A total of 68 hospitalized patients with acute pelvic inflammatory disease were entered and randomized into two treatment groups: cefotetan (n = 32) and cefoxitin (n = 36). There were six tuboovarian abscesses in each group. C. trachomatis was recovered from 7 (10%) and N. gonorrhoeae from 48 (71%) of the patients. Anaerobic and aerobic bacteria were recovered from the upper genital tract in 53 (78%) of the patients. Cefotetan plus doxycycline and cefoxitin plus doxycycline demonstrated high rates of initial clinical response in the treatment of acute pelvic inflammatory disease. Clinical cure was noted in 30 (94%) of the cefotetan plus doxycycline group and 33 (92%) of the cefoxitin plus doxycycline group. Four failures were sonographically diagnosed tuboovarian abscesses that responded to clindamycin plus gentamicin therapy. The fifth failure was an uncomplicated case that did not respond to cefoxitin and doxycycline and required additional therapy. At 1 week and 3 weeks, respectively, the posttreatment cultures demonstrated eradication, in all instances, of N. gonorrhoeae and C. trachomatis. These regimens also were very effective in eradicating anaerobic and aerobic pathogens from the endometrial cavity. Both regimens were well tolerated by the patients, and few adverse drug affects were noted.

Acute Disease↗

Ampicillin/sulbactam and cefoxitin in the treatment of cutaneous and other soft-tissue abscesses in patients with or without histories of injection drug abuse.

A randomized, double-blind trial compared the clinical and bacteriologic efficacy of ampicillin/sulbactam (2 g/1 g) and cefoxitin (2 g) administered intravenously every 6 h to patients with (n=49) or without (n=47) histories of injection drug abuse who presented with cutaneous or other soft-tissue infections. Cure or improvement occurred in 89.8% of ampicillin/sulbactam-treated patients, compared with 93.6% of cefoxitin-treated patients. The median time to resolution of all symptoms was 10.5 days with ampicillin/sulbactam treatment and 15.5 days with cefoxitin treatment. Mixed aerobic-anaerobic infection was encountered frequently in both treatment groups. A significantly higher percentage of Streptococcus species was found in the major abscesses of the patients with histories of injection drug abuse, compared with those without such histories (37% vs. 19%, respectively; P=.0009). Overall, ampicillin/sulbactam eradicated pathogens from the major abscesses in 100% of patients, whereas the eradication rate with cefoxitin was 97.9%. The 2 drugs were well tolerated. Ampicillin/sulbactam and cefoxitin were equally effective for the empirical treatment of cutaneous or other soft-tissue infections in injection drug abusers and patients who did not inject drugs.

Abscess↗

A sheep preparation for studying interactions between blood flow and drug disposition. IV: The effects of general and spinal anaesthesia on blood flow and cefoxitin disposition.

Control measurements of blood flow through and cefoxitin extraction ratios across heart and lungs, liver, kidneys and gut were made under steady-state conditions in awake unrestrained sheep. The studies then were repeated with the same animals anaesthetized with 1.5% halothane or whilst undergoing high thoracic (to approximately T4) subarachnoid blockade with amethocaine. In the control-drug studies, it was shown that cefoxitin was cleared by the kidneys and that the cefoxitin infusion produced no significant changes in haemodynamics or in the kinetics of iodohippurate (the marker substance used for determining renal blood flow). Under general anaesthesia, there were significant reductions in renal blood flow (to 61% of the mean control value), in iodohippurate renal extraction ratio and clearance (to, respectively, 64 and 38% of the mean control values) and in cefoxitin renal extraction ratio and clearance (to, respectively, 48 and 23% of the mean control values). Under spinal anaesthesia there were no significant changes in haemodynamics or in cefoxitin or iodohippurate extraction ratios or clearances.

Anesthesia, General↗

Treatment of significant bacterial infections in adults with cefoxitin.

Cefoxitin is a new antimicrobial agent derived from cephamycin C. Fifty-four hospitalized patients with 63 clinically significant infections were treated with cefoxitin. Fifty-four infections (86%) were cured by therapy with cefoxitin alone or together with local therapy (i.e., heat, elevation, or surgical drainage). Six infections (10%) were not eradicated by the therapy used. Three patients could not be evaluated. Addition of oral probenecid therapy produced increases in levels of cefoxitin in serum and increased the inhibitory and bactericidal levels of cefoxitin in serum to more favorable ratios. Adverse side effects were seen in 19 patients and included positive direct Coombs' tests, increased eosinophil counts, skin rashes, vasculitis, phlebitis, elevation of liver enzymes, and drug-induced fever.

Adult↗

Clinical evaluation of cefoxitin in the treatment of respiratory tract and other acute bacterial infections.

A clinical trial was designed for evaluation of the efficacy, safety, and patient tolerance of cefoxitin. Of 26 patients who could be evaluated clinically, 21 had respiratory tract infections; all but one patient responded satisfactorily to therapy with cefoxitin. There were no adverse systemic reactions, nor was any renal or hematologic toxicity noted. In two instances levels of hepatic enzymes became slightly elevated; these changes were possibly related to administration of cefoxitin. About one-third of patients receiving cefoxitin developed minor local reactions at the site of intravenous administration; however, there was only a single instance of true thrombophlebitis. Results of this study suggest that cefoxitin is a safe and well-tolerated antibiotic that is efficacious in therapy of acute respiratory tract infections caused by bacteria that are sensitive to this drug.

Acute Disease↗

Cefoxitin therapy for bacterial endocarditis.

Of 22 patients who were suspected of having bacterial endocarditis and who were treated with cefoxitin intravenously (8-12 g per day), 12 were evaluated for responses to therapy. Ten patients had infections due to a single pathogen, and two had polymicrobial infections. Staphylococci were isolated from eight patients, and streptococci from four; both of these pathogens were susceptible to 2-16 micrograms of cefoxitin/ml. Staphylococcus aureus and four strains of anaerobic bacteria, including Bacteroides fragilis (minimal inhibitory concentration, 32 micrograms/ml), were isolated from one patient. The average level of cefoxitin in serum was 32.8 micrograms/ml (range, 14.5-64 micrograms/ml) at 1 hr after an intravenous dose of 2 g; after 5 hr the average level in serum was 8.5 micrograms/ml (range, 2-20 micrograms/ml). The mean (+/- SD) level of cefoxitin in myocardial tissues from eight rabbits at 1 hr following a 250-mg/kg dose of the antibiotic was 4 +/- 0.5 micrograms/g. On the average, patients were treated for 29 days (range, 14-40 days), and they became afebrile in 6.2 days (range, three to 20 days). Both clinical and microbiologic responses to cefoxitin therapy were excellent in 10 patients with monobacterial infections. Both patients with polymicrobial infections were not cured. One, who was infected with a mixed flora of anaerobes, died; the other was cured after surgical valvectomy. These results suggest that cefoxitin is effective in the treatment of endocarditis due to a single susceptible organism but that this antibiotic should be used with caution in patients whose endocarditis is caused by a mixed population of bacterial pathogens.

Adult↗

Cefoxitin therapy for surgical patients.

Cefoxitin was administered to 25 patients on a general surgical service. In 16 of these patients, a bacteriologic diagnosis was made: four patients had peritonitis, one had ascending cholangitis, seven had cellulitis, and four had abscess. The dosage of cefoxitin varied from 4 to 8 g per day and was generally well tolerated, although there were three cases of phlebitis and one superinfection. There was no evidence of renal, liver, or bone marrow toxicity. All isolates of Bacteroides (eight), Escherichia coli (six), and Staphylococcus aureus (five) were sensitive to cefoxitin. Two of three strains of Pseudomonas aeruginosa were resistant. All patients recovered with cefoxitin and corrective surgery. The results indicate that cefoxitin has the potential of replacing combination therapy in some surgical patients.

Abscess↗

In vitro activity of cefoxitin and parenterally administered cephalosporins against anaerobic bacteria.

The in vitro activity of cefoxitin against 221 recent isolates of anaerobic bacteria was compared with that of cefamandole and cefuroxime by the agar dilution technique. At achievable serum levels of 32 micrograms/ml, all three drugs were active against most groups of anaerobic bacteria tested. Cefoxitin was active against most strains of the Bacteroides fragilis group, whereas cefamandole and cefuroxime were relatively ineffective. Cefoxitin was least active against Clostridium species other than Clostridium perfringens, whereas cefamandole was very active and cefuroxime moderately active. A review of recent in vitro studies with cefoxitin and parenterally administered cephalosporins indicates that cefoxitin is the most active compound against the B. fragilis group and is least active against Clostridium species other than C. perfringens.

Bacteria, Anaerobic↗

Intramuscular cefoxitin.

Cefoxitin was administered by the intramuscular route to 102 patients who had infections of mild or moderate severity. The assessment of clinical and bacteriologic outcome was derived from data for 79 patients. Assessments of tolerance and safety were made for all patients who received 1 g of cefoxitin diluted in 1 ml of 0.5% or 1.0% lidocaine four times daily. Cure or improvement occurred in 45 of 47 patients with skin or soft tissue infections, in all of 16 patients with lower respiratory tract infections, and in 10 of 12 patients with urinary tract infections. One patient developed acute tubular necrosis. Eosinophilia was seen in 7% of patients treated with cefoxitin. The intramuscular preparation was not painful to 96% of the patients. Cefoxitin given by the intramuscular route can be used as an alternative to intravenous cefoxitin for treatment of mild or moderate infections, for continuation of treatment when the intravenous route is not appropriate, and for treatment of ulcers of polymicrobial etiology on ischemic extremities or on extremities of diabetic patients.

Abscess↗

Synergistic activity of cefsulodin combined with cefoxitin and sulbactam against Bacteroides species.

The in-vitro activity of cefsulodin combined with sulbactam, cefoxitin or cefotaxime was investigated against 32 strains of beta-lactamase-producing Bacteroides species. Synergy of cefsulodin-sulbactam or cefsulodin-cefoxitin could be demonstrated against 30 of 32 and 32 of 32 strains tested at the concentrations readily achievable in serum. In the presence of 1 mg/l of sulbactam or cefoxitin, more than 90% of the Bacteroides isolated were inhibited by 32 mg/l of cefsulodin. The inhibitory activity of cefsulodin-sulbactam or cefsulodin-cefoxitin combinations was bactericidal against Bact. fragilis and Bact. vulgatus. In contrast, no synergistic inhibitory or bactericidal activities can be observed by the cefsoludin-cefotaxime combination. Both sulbactam and cefoxitin were potent inhibitors of beta-lactamases produced by Bact. fragilis and Bact. melaninogenicus suggesting that this inhibitory activity might be one of the factors contributing to the synergistic combinations.

Bacteroides↗

Cefoxitin versus gentamicin and metronidazole in prevention of post-appendicectomy sepsis: a randomized, prospective trial.

Three hundred and seven patients with appendicitis were randomized to receive cefoxitin or gentamicin and metronidazole. For early appendicitis, a single preoperative dose of antibiotics was given. For late cases, the antibiotics were continued postoperatively for seven days. Both cefoxitin and gentamicin-metronidazole were effective in the reduction of post-appendicectomy septic complications in early or late appendicitis and there was no statistically significant difference between them. Mild transient and reversible nephrotoxicity was detected in 1.9% of patients who received gentamicin-metronidazole for seven days. Nephrotoxicity was not detected in any other patients. The cost of cefoxitin is higher, but this has to be balanced against the costs of monitoring serum gentamicin and creatinine levels, and the need to adjust the gentamicin dosage in 19% of patients when gentamicin-metronidazole was used. Both cefoxitin and gentamicin-metronidazole are effective and safe when used carefully. Cefoxitin has a slight advantage in its lack of potential nephrotoxicity and ototoxicity.

Adolescent↗

Comparative evaluation of safety and efficacy of cefmetazole and cefoxitin in lower respiratory tract infections.

The efficacy and safety of cefmetazole and cefoxitin were compared in a randomized open-label parallel trial in 68 hospitalized adult patients with lower respiratory tract infections. Of 40 patients evaluable for efficacy, 23/25 (92%) in the cefmetazole group and 13/15 (87%) in the cefoxitin group demonstrated a favourable clinical response. The causative bacteria were eradicated in 30/32 (94%) and 13/14 (93%) of isolates in the cefmetazole and cefoxitin groups, respectively. A total of 51 adverse events was noted in 68 patients: 36 in 26 patients (55%) in the cefmetazole group and 15 in 12 patients (57%) in the cefoxitin group. These events were reversible, and except in one patient who was treated for oral candidiasis, did not require any therapeutic intervention or prolonged hospitalization. Cefmetazole appears to be as safe and effective as cefoxitin in the treatment of lower respiratory tract infections of hospitalized patients.

Aged↗