Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment.

BACKGROUND: Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. METHODS: We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. RESULTS: Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. CONCLUSIONS: The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.

Observation on Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section.

This paper aims to observe the effect of Shenqi Fuzheng Injection combined with cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were retrospectively analyzed. They randomized into control group and treatment group, and there were 63 cases in each group. Patients in control group were given Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi Fuzheng Injection on the basis of control group. After 7 days of treatment, the clinical curative effect of the two groups was observed and compared. The body temperature of the patients in treatment group was significantly decreased when compared with control group on the 2nd and 3rd day after operation (P<0.05); the first exhaust time and defecation time of patients in treatment group were significantly shortened when compared with control group (P<0.05); the postoperative hemoglobin and red blood cell count in both groups were all significantly increased when compared with before treatment (P<0.05), and the treatment group were evidently higher than control group (P<0.05); the postoperative neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in both groups were all significantly lowered when compared with before treatment (P<0.05), and the neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in treatment group were significantly lowered when compared with control group (P<0.05). Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section can effectively reduce the postoperative maternal body temperature and promote the recovery of maternal gastrointestinal function, which is conducive to the repair of uterus, further correct anemia after cesarean section and prevent postpartum infection. Its clinical curative effect is ideal, with certain clinical application value.

A severe case of cefoxitin-induced immune hemolytic anemia.

Drug-induced immune hemolytic anemia is a rare but underdiagnosed and potentially fatal condition. We report a case of severe hemolytic anemia induced by cefoxitin in a 45-year-old woman admitted with menometrorrhagia. Hemoglobin levels reached a nadir of 4.7 g/dl approximately 72 h after cefoxitin initiation, and hemolysis resolved when cefoxitin was discontinued and prednisone 1 mg/kg was initiated. A transfusion reaction workup revealed no abnormalities. Direct antiglobulin testing was weakly positive with anti-C3. The patient's plasma and RBC eluate reacted with cefoxitin-treated RBCs but not with untreated RBCs in the presence or absence of cefoxitin.

Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients.

RATIONALE: The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established. OBJECTIVES: To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease. METHODS: Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization. MEASUREMENTS AND MAIN RESULTS: Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days. CONCLUSIONS: Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

Cephalosporin-induced leukopenia following rechallenge with cefoxitin.

OBJECTIVE: To describe a case of cefazolin-induced leukopenia in a critically ill patient who developed this adverse reaction upon rechallenge with cefoxitin. CASE SUMMARY: A 22-year-old male was admitted after a motor vehicle crash. beta-Lactam therapy was initiated with vancomycin, cefepime, and metronidazole and, upon identification of methicillin-sensitive Staphylococcus aureus bacteremia 4 days later, therapy was narrowed to cefazolin 1 g every 12 hours. The dose was adjusted to 1 g every 12 hours during continuous venovenous hemodialysis. Imipenem was given for 2 days, resulting in a total of 18 days of beta-lactam treatment, at which time he developed significant leukopenia (white blood cell [WBC] count 0.9 x 10(3)/microL). Antimicrobial treatment was changed to tigecycline and continued for suspected pleural space infection. The patient's WBC count recovered within 4 days after the change in therapy. He was taken to surgery 8 days after cefazolin was discontinued and received perioperative prophylaxis with cefoxitin (total dose 3 g). Subsequently, the patient again became severely leukopenic (WBC count 2.4 x 10(3)/microL). Within a week after surgery, the patient developed septic shock secondary to multidrug-resistant Escherichia coli bacteremia and died. DISCUSSION: beta-Lactam-induced leukopenia is a rare but well-described adverse drug reaction. It is a cumulative dose-dependent phenomenon reported to occur most often after 2 weeks of therapy. The mechanism of leukopenia is thought to be secondary to either an immune-mediated response or direct bone marrow toxicity. Rechallenge with a different beta-lactam antibiotic has not been shown to consistently cause recurrent leukopenia. The case described here suggests an immune-related mechanism for the development of leukopenia. Use of the Naranjo probability scale determined the association between cephalosporin use and leukopenia to be probable. CONCLUSIONS: Cefazolin was a probable cause of this patient's leukopenia. It is important for clinicians to recognize beta-lactam-induced leukopenia and maybe recommend use of a drug from a different antibiotic class if continued treatment is indicated.

Higher versus Lower Dose of Cefotetan or Cefoxitin for Surgical Prophylaxis in Patients Weighing One Hundred Twenty Kilograms or More.

BACKGROUND: Clinical practice guidelines recommend a 2-g dose of cefotetan and cefoxitin for surgical prophylaxis. Pharmacokinetic data suggest benefit from higher cefotetan and cefoxitin dosing in obese patients. However, clinical studies examining higher dosing strategies in this at-risk population are lacking. The purpose of this study was to determine whether 3 g of cefotetan or cefoxitin administered pre-operatively for patients who weigh 120 kg or more is associated with a lower proportion of surgical site infection (SSI) compared with 2 g. PATIENTS AND METHODS: Medical records of patients weighing 120 kg or more who had received cefotetan or cefoxitin (2 or 3 g) as surgical prophylaxis for intra-abdominal procedures between July 2012 and August 2015 were reviewed for the development of an SSI (primary outcome), study drug-related adverse events, and re-admissions attributed to SSIs (secondary outcomes). Relative risk calculations were performed for analysis of the primary and secondary outcomes. RESULTS: One-hundred seventy-five procedures in 169 patients were included in the study. Cefotetan was used in 81% (141/175) of procedures. Three grams of cefotetan or cefoxitin was used in 20% (35/175) of procedures. The median body mass index (BMI) in both dosing groups was 42 kg/m2 and patients who received 3 g more often weighed more than 130 kg (relative risk [RR] 1.36, 1.01-1.76; p = 0.04). Surgical site infections occurred in 20.7% within the 2-g group and 22.9% in the 3-g group (RR 1.10, 0.55-2.20; p = 0.78). There was no difference in the number of study drug-related adverse effects in the 3-g compared with the 2-g group. Thirty-day re-admissions because of SSI also did not differ between the 2-g and 3-g groups (7.9% vs. 17.1%, respectively; p = 0.11). CONCLUSION: This small retrospective study did not find a difference in SSI rates between 3-g and 2-g surgical prophylaxis dosing for patients 120 kg or more with a median BMI >40 kg/m2.

Cefoxitin: An alternative to carbapenems in urinary tract infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae.

BACKGROUND AND OBJECTIVES: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL. PATIENTS AND METHODS: We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria. RESULTS: We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment. CONCLUSION: Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients.

Most cases of beta-lactam-associated coagulopathy occur in patients with other risk factors. This study analyzed temporally related clinical bleeding events in 1493 patients who received one antibiotic for at least three days. Univariate and multivariate analyses controlled for condition variables (nutritional status, renal, hepatic, or hematologic dysfunction, intensive care unit stay) and treatment variables (use of antiplatelet agents, anticoagulants, vitamin K, antitumor chemotherapy or antiulcer therapy, steroids) that could have been associated with bleeding independently. Rates of bleeding ranged from 0% (chloramphenicol sodium succinate, vancomycin hydrochloride, erythromycin lactobionate) to 8.2% (cefoxitin) to 22.2% (moxalactam disodium). Multiple logistic regression analyses revealed that only moxalactam (odds ratio, 9.9) and cefoxitin (odds ratio, 2.1) exhibited significantly higher likelihoods of bleeding than other agents. This study statistically confirms increased risk of bleeding with moxalactam, heretofore reported only anecdotally. Cefoxitin may carry risks greater than previously believed.

Exfoliative dermatitis during cefoxitin therapy.

An 84-year-old man was admitted to the hospital with a diabetic foot ulcer and osteomyelitis of the calcaneum. While being treated with cefoxitin sodium, he experienced generalized exfoliative dermatitis, which subsided on discontinuation of therapy. To our knowledge, this is the first report of exfoliative dermatitis with a cephalosporin or related drug.

Combination amdinocillin and cefoxitin therapy of multiply-resistant Serratia marcescens urinary tract infections.

Amdinocillin has previously been shown to be synergistic with other beta-lactam antibiotics against many gram-negative bacteria. We evaluated the safety, efficacy, and microbiologic activity of combination amdinocillin and cefoxitin treatment in 17 patients with complicated urinary tract infections caused by multiply-resistant Serratia marcescens. Patients were treated with amdinocillin, 40 mg/kg per day, and cefoxitin, 100 mg/kg per day, for five to 14 days. In vitro synergistic activity was observed for 17 isolates using broth checkerboard testing and for nine isolates using combination disc diffusion testing. Of the 17 patients treated, 11 were bacteriologically cured, one failed to respond, and five patients had a relapse after initial improvement. Relapses followed short-duration therapy. Amdinocillin with cefoxitin was well tolerated. Combination amdinocillin and cefoxitin therapy was efficacious and safe in treating complicated urinary tract infections caused by multiply-resistant S. marcescens.

Amdinocillin plus cefoxitin versus cefoxitin alone in therapy of mixed soft tissue infections (including diabetic foot infections).

In a randomized comparative trial, 45 patients were treated with amdinocillin plus cefoxitin or cefoxitin alone for bacterial soft tissue infections. Most patients were diabetic and had polymicrobial foot infections. The combination of amdinocillin plus cefoxitin was active in vitro against 71 percent of the isolates obtained before therapy as compared with 65 percent for cefoxitin alone. The combination demonstrated synergy for 29 percent of the isolates tested. A satisfactory clinical response occurred in 90 percent and 71 percent of patients treated with the combination regimen and cefoxitin, respectively, (p greater than 0.1). An increase in serum creatinine thought to be due to interstitial nephritis occurred in one patient treated with the combination regimen. The combination of amdinocillin and cefoxitin was effective in mixed soft tissue infections including diabetic foot infections.

Reversible acute cardiac injury during cefoxitin-induced anaphylaxis in a patient with normal coronary arteries.

This report describes a 64-year-old patient who had electrocardiographic evidence of acute cardiac injury but no ensuing myocardial infarction as a complication of systemic anaphylaxis from intravenous cefoxitin. Coronary angiography subsequently demonstrated essentially normal findings except for anomalous origin of the right coronary artery from the left sinus of Valsalva. There is believed to be only one previous report of coronary angiography in a patient who had a myocardial infarction complicating an anaphylactoid reaction to radiographic dye; in that patient, angiography showed coronary atherosclerosis. The possible role of coronary vasospasm in cardiac injury complicating anaphylaxis is discussed.

Cefoxitin: a review of its antibacterial activity, pharmacological properties and therapeutic use.

Cefoxitin is a beta-lactam antibiotic derived from cephamycin C, a naturally occurring substance produced by Streptomyces lactamdurans. Its resistance to destruction by beta-lactamases results in a broad spectrum of antibacterial activity which includes anaerobic as well as Gram-positive and Gram-negative aerobic bacteria, including many resistant to cephalothin and other cephalosporins. Given by intravenous or intramuscular injection, cefoxitin is effective against a wide variety of infections caused by Gram-positive or Gram-negative aerobes as well as by anaerobic bacteria. It is generally well tolerated, thrombophlebitis, skin rash and some degree of discomfort after intramuscular injection, being the most commonly reported side effects. Cefoxitin has not been shown to cause adverse effects on renal function.

Sulbactam/ampicillin versus cefoxitin for uncomplicated and complicated acute pelvic inflammatory disease.

In this study, 17 women were treated for uncomplicated acute pelvic inflammatory disease requiring hospitalisation for therapy, and 5 women were treated for the same infection complicated by pelvic abscesses. Treatment regimens were sulbactam 1g plus ampicillin 2g (14 women) or cefoxitin 2g (8 women) given by intravenous infusion every 6 hours. On the third day of therapy, a rash developed in 1 woman who was being successfully treated for uncomplicated disease with sulbactam/ampicillin. The other 21 women were cured. No other adverse clinical reactions and no significant abnormal laboratory results were observed with either regimen. Bacteriological efficacy, 98% for sulbactam/ampicillin and 94% for cefoxitin, closely paralleled clinical efficacy. Sulbactam, a suicide-type beta-lactamase inhibitor, appears to have restored and expanded the antibacterial activity of ampicillin.

Cefoxitin for prophylaxis in premenopausal women undergoing vaginal hysterectomy.

To determine the unbiased incidence and types of postoperative infection and their alteration(s) by antimicrobial prophylaxis, a prospective double-blind study was performed using perioperative intramuscular cefoxitin or placebo given to premenopausal women undergoing vaginal hysterectomy at Parkland Memorial Hospital. The clinical and surgical profiles of the 2 groups of women were similar, but there were marked differences in their postoperative clinical courses. Only 8% of the 50 women given cefoxitin had major postoperative infection, compared to 57% of the 49 women given placebo (P < .001); this was associated with a 2.8-day reduction in the hospital stay for those given cefoxitin (P < .001). No clinically significant side effects were observed.

Comparative efficacy and safety of mezlocillin, cefoxitin, and clindamycin plus gentamicin in postpartum endometritis.

The efficacy of mezlocillin versus cefoxitin versus clindamycin plus gentamicin was evaluated in 152 patients with postpartum endometritis. There were no statistically significant differences in rate of cure among the three groups (87% with mezlocillin, 82% with cefoxitin, and 92% with clindamycin-gentamicin). There were no severe adverse reactions observed in any of the three treatment regimens. Mezlocillin is as safe and effective as cefoxitin and clindamycin-gentamicin for treatment of postpartum endometritis.

Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis.

OBJECTIVE: To evaluate the efficacy and safety of ampicillin-sulbactam (3 g every 6 hours) in patients with pelvic inflammatory disease or postpartum endometritis using a randomized, comparative, multicenter study of parallel design. METHODS: Eligible patients with pelvic inflammatory disease were randomized to receive either ampicillin-sulbactam or cefoxitin (2 g every 6 hours) plus doxycycline (100 mg every 12 hours). Those with endometritis were randomized to ampicillin-sulbactam or clindamycin (900 mg every 8 hours) plus gentamicin (1.5 mg/kg every 8 hours). In the ampicillin-sulbactam group, chlamydia-positive patients also received oral doxycycline. RESULTS: For pelvic inflammatory disease, the clinical response rates (cure or improvement) were 85.5% (47 of 55) and 89.6% (43 of 48) in the ampicillin-sulbactam and cefoxitin and doxycycline groups, respectively (chi 2 = 0.10, P = .76). For endometritis, the clinical response rates were 88.7% (141 of 159) and 90.8% (139 of 153) in the ampicillin-sulbactam and clindamycin and gentamicin groups, respectively (chi 2 = 0.15, P = .70). The percentages of patients with pelvic inflammatory disease who had adverse experiences were not significantly different in the cefoxitin and doxycycline group (47% [29 of 62]) than in those receiving ampicillin-sulbactam (33% [22 of 66]) (P = .12). These adverse effects were mostly mild or moderate. In the endometritis subjects, the incidence of adverse experiences in the ampicillin-sulbactam group (11% [20 of 179]) was comparable to that during treatment with clindamycin and gentamicin (12% [22 of 180]). These adverse experiences were also mostly mild to moderate. CONCLUSION: Ampicillin-sulbactam is as effective and well tolerated as combination regimens using cefoxitin plus doxycycline and clindamycin plus-gentamicin for the treatment of pelvic inflammatory disease or endometritis, respectively.

Outpatient treatment of pelvic inflammatory disease with cefoxitin and doxycycline.

Sixty-three women with abdominal pain and adnexal tenderness were enrolled in a study of ambulatory treatment of acute pelvic inflammatory disease. Treatment consisted of 2 g of cefoxitin intramuscularly and 1 g of probenecid orally, followed by doxycycline, 100 mg by mouth twice daily for 14 days. Patients were stratified into groups indicating whether pelvic inflammatory disease was probable, possible, or unlikely, based upon endometrial biopsy and clinical criteria. Among 52 women who were evaluated, Chlamydia trachomatis and/or Neisseria gonorrhoeae were initially recovered from 16 (67%) of 24 with probable pelvic inflammatory disease, three (33%) of 11 with possible pelvic inflammatory disease, and three (18%) of 17 in whom pelvic inflammatory disease was considered unlikely. Of the 24 patients with probable pelvic inflammatory disease, 22 (92%) were clinically cured or improved. Of 22 patients initially infected with C trachomatis and/or N gonorrhoeae, 20 were culture-negative for both organisms after therapy. Both microbiologic failures had been reexposed. This study suggests that the combination of cefoxitin and doxycycline is effective for ambulatory treatment of pelvic inflammatory disease.

A randomized, double-blind, placebo-controlled trial of oral antibiotic therapy following intravenous antibiotic therapy for postpartum endometritis.

One hundred thirty-six patients were enrolled in a randomized, double-blind, placebo-controlled trial of oral antibiotic therapy (amoxicillin) versus placebo following successful intravenous (IV) antibiotic therapy for postpartum endometritis. No subjects were readmitted to the hospital for recurrent endometritis and there were no wound infections or recurrent fevers. Minor side effects were seen in 10% of those taking amoxicillin and 14% of those taking placebo. Compliance was fair; only 52% of those taking amoxicillin and 65% of those taking placebo completed therapy. The lack of infectious complications in this high-risk population suggests that oral antibiotic therapy is unnecessary after successful IV antibiotic therapy for endometritis.