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.

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.

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.

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.

Antibiotic exposure and IBD development among children: a population-based cohort study.

OBJECTIVE: To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD). METHODS: This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥ 2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/ß-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin. RESULTS: A total of 1072426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25) and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13-10.68) versus 3.33 (95% CI: 1.69-6.58). CONCLUSIONS: Childhood antianaerobic antibiotic exposure is associated with IBD development.

Disseminated Mycobacterium avium subspecies infection in a cat.

An 18-month-old neutered male domestic shorthair cat, domiciled in the southwest of France, was first presented having suffered for a few days from dysorexia and vomiting. Abdominal palpation revealed lymph node enlargement. Cytological examinations of a fine needle aspirate demonstrated granulomatous inflammation with many non-staining elements consistent with mycobacteria. Diagnosis was confirmed by culture and polymerase chain reaction and Mycobacterium avium subspecies was isolated. Treatment was initiated with marbofloxacin, rifampicin and cefoxitin. There was a rapid clinical improvement. The cat suddenly died 2 months later. The main hypothesis is the administration of an inappropriate combination therapy that leads to the development of mycobacterial resistance. A volvulus and acute peritonitis secondary to the significant enlargement of a mesenteric lymph node were present at necropsy. Histopathological analysis of mesenteric lymph node, liver and spleen revealed multicentric granulomatous and severely necrotic lesions with numerous Ziehl-Neelsen positive intracytoplasmic elements.

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.

Treatment of fistulas-in-ano with fibrin sealant in combination with intra-adhesive antibiotics and/or surgical closure of the internal fistula opening.

PURPOSE: The treatment of fistulas-in-ano with fibrin sealant injection has been moderately successful. Failures can be caused by persistent infection within the tract or early expulsion of the clot. In an attempt to improve the success rate, we examined three modifications of the sealant procedure: the addition of cefoxitin to the sealant, surgical closure of the primary opening, or both. METHODS: A prospective, randomized, clinical trial was performed in which patients were treated with Tisseel-VH fibrin sealant according to previously published procedures. In addition, patients were randomized to receive intra-adhesive cefoxitin, surgical closure of the primary opening, or both modifications. Cefoxitin, 100 mg, was added to the sealant for patients randomized to receive intra-adhesive antibiotics. For the appropriate patients, the primary fistula opening was closed with a 3-0 absorbable suture. If fistulas failed to heal, patients were offered a single retreatment with sealant. RESULTS: Twenty-four patients were treated in the cefoxitin arm, 25 in the closure arm, and 26 in the combined arm. Median duration of fistulas was 12 months. Patients were followed for a mean of 27 months postoperatively. There was no postoperative incontinence or complications related to the sealant itself. Initial healing rates were 21 percent in the cefoxitin arm, 40 percent in the closure arm, and 31 percent in the combined arm (P = 0.35). One of five patients in the cefoxitin arm, one of seven patients in the closure arm, and one of six patients in the combined arm were successfully retreated; final healing rates were 25, 44, and 35 percent respectively (P = 0.38). CONCLUSIONS: Treatment of fistula-in-ano with fibrin sealant with closure of the internal opening was somewhat more successful than sealant with cefoxitin or the combination, however this did not achieve statistical significance. None of the three modifications were more successful than historic controls at our institution treated with sealant alone. Therefore, the addition of intra-adhesive cefoxitin, closure of the internal opening, or both are not recommended modifications of the fibrin sealant procedure.

Molecular ecological analysis of dietary and antibiotic-induced alterations of the mouse intestinal microbiota.

A cultivation-independent approach, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), was used to characterize changes in fecal bacterial populations resulting from consumption of a low residue diet or oral administration of a broad-spectrum antibiotic. C57BL/6NHsd mice were weaned to either a standard nonpurified diet (LC-diet) or a low residue diet (LR-diet) and at 17 wk of age were randomly assigned to receive drinking water with or without 25 ppm cefoxitin for 14 d. On d 1, 2, 7 and 14, microbial DNA was extracted from feces, and the V3 region of the 16S rDNA gene was amplified by PCR and analyzed by DGGE. The diversity of fecal microbial populations, assessed using Shannon's index (H'), which incorporates species richness (number of species, or in this case, PCR-DGGE bands) and evenness (the relative distribution of species), was not affected by cefoxitin. However, use of Sorenson's pairwise similarity coefficient (C(s)), an index that measures the species in common between different habitats, indicated that the species composition of fecal bacterial communities was altered by cefoxitin in mice fed either diet. Dietary effects on fecal microbial communities were more pronounced, with greater H' values (P < 0.05) in mice fed the LR-diet (1.9 +/- 0.1) compared with the LC-diet (1.6 +/- 0.1). The C(s) values were also greater (P < 0.05) in fecal bacterial populations from mice fed the LR-diet (C(s) = 69.8 +/- 2.0%) compared with mice fed the LC-diet (C(s) = 50.1 +/- 3.8%), indicating greater homogeneity of fecal bacterial communities in mice fed the LR-diet. These results demonstrate the utility of cultivation-independent PCR-DGGE analysis combined with measurements of ecological diversity for monitoring diet- and antibiotic-induced alterations of the complex intestinal microbial ecosystem.

[Efficacy and safety of two cephalosporins in the perioperative prophylaxis in patients undergoing abdominal or vaginal hysterectomies or gynaecological laparotomies: a prospective randomized study]. / Wirksamkeit und Verträglichkeit zweier Zephalosporine in der perioperativen Antibiotikaprophylaxe bei abdominalen und vaginalen Hysterektomien und gynäkologischen Laparotomien. Eine prospektiv randomisierte Studie.

The aim of this study was to compare efficacy and safety of perioperative antibiotic prophylaxis in patients undergoing abdominal or vaginal hysterectomy or gynaecological laparotomy to improve the prevention of surgical wound infections. One hundred and ninety-nine patients were prospectively randomized into two groups: the first group (n = 100) received perioperative prophylaxis using 1 g cefotiam (Spizef) and 0.5 g metronidazole (Clont) intravenously 30 min before surgery, whereas the second group (n = 99) was treated with 2 g cefoxitin (Mefoxitin) intravenously, also 30 min before surgery. The efficacy of the perioperative antibiotic prophylaxis was assessed clinically and on the basis of laboratory parameters. No wound infections were observed in 97 patients (97%) of the cefotiam-treated group and in 94 patients (94%) of the cefoxitin-treated group. No systemic postoperative infections were observed in 81% of the patients treated with cefotiam combined with metronidazole and in 85% of the patients treated with cefoxitin. The good tolerability of the drugs administered was proven in 98% of the patients treated with cefotiam and metronidazole and in 97% of the patients treated with cefoxitin. In both groups 3 patients developed nausea and/or vomiting, respectively, due to the antibiotic prophylaxis. A low infection rate after gynaecological surgery was observed. Cefotiam as a low dosage combined with metronidazole was as effective as cefoxitin. Cephalosporins of the second generation in combination with metronidazole can, therefore, be considered effective and safe drugs in the prevention of postsurgical infections.

Clostridium difficile infection in obstetric and gynecologic patients.

We reviewed hospital records of women on the obstetrics and gynecologic services with a diagnosis of antibiotic-associated diarrhea, pseudomembranous colitis, or Clostridium difficile infection to better characterize the incidence and course of women with C difficile infection. Cases were included if there was identification of C difficile by culture or toxin or endoscopic verification of pseudomembranous colitis. Between January 1985 and June 1995, there were 74,120 admissions to the obstetrics and gynecology services at two tertiary level hospitals. Eighteen women were found to have documented C difficile infection (0.02%)--3 from the obstetric services, 10 from the benign gynecologic services, and 5 from the gynecologic/oncology services. Diarrhea developed from 2 days to 30 days after antibiotics had been given (mean, 10 days). Nine patients had fever, six had nausea and vomiting, and five had abdominal pain. Antimicrobial agents given before infection included cephalexin, cefoxitin, imipenem, ciprofloxacin, trimethoprim/sulfamethoxazole, ampicillin, gentamicin, and clindamycin. All patients were treated successfully with inpatient antimicrobial agents-15 with metronidazole and 3 with vancomycin. There was one possible recurrence.

Comparison of single-dose cefotetan and multidose cefoxitin as intravenous prophylaxis in elective, open biliary tract surgery: a multicentre, double-blind, randomized study.

OBJECTIVE: To compare the safety, tolerance and prophylactic effectiveness of a single 2-g dose of cefotetan with a standard prophylactic regimen of cefoxitin in reducing the incidence of postoperative infections after elective, open biliary tract surgery. DESIGN: Multicentre, double-blind, randomized comparative study with a 4-week follow-up. SETTING: Five Canadian university centres. PARTICIPANTS: One hundred and eleven patients scheduled to undergo elective, open biliary tract surgery. INTERVENTIONS: The patients were randomly assigned to receive either cefotetan or cefoxitin in a ratio of 2:1; 76 patients received cefotetan and 35 received cefoxitin. MAIN OUTCOME MEASURES: Wound infection as defined by the Centers for Disease Control and Prevention and by clinical evaluation, adverse events and laboratory parameters. RESULTS: Two incisional wound infections were reported by patients in the cefotetan group, for an overall infection rate of 1.8% (2 of 111). No significant differences were found in the failure rate or in any other indicator of efficacy. The incidence of adverse events for cefotetan (12.6%) was not statistically different from that for cefoxitin (10.4%), and none of the 16 adverse events in the cefotetan group and 5 in the cefoxitin group was serious or severe. Only one event (rash) was possibly related to the study drugs. Several hematologic and biochemical parameters were found to be normal preoperatively and abnormal postoperatively, but no relation was found between these variations and the study drugs. These changes were mainly attributable to the operation. CONCLUSION: Cefotetan was found to be effective and comparable to cefoxitin, both in safety and in reducing the incidence of infection after elective, open biliary tract surgery.

[Ciprofloxacin/metronidazole vs. cefoxitin/doxycycline: comparison of two therapy schedules for treatment of acute pelvic infection]. / Ciprofloxacin/Metronidazol vs. Cefoxitin/Doxycyclin: Vergleich zweier Therapieschemata zur Behandlung der akuten pelvinen Infektion.

The efficacy and safety of two antibiotic regimens for the treatment of acute pelvic inflammatory disease (PID) was compared in a prospective and randomised study. 57 patients received either 0.2 gms ciprofloxacin intravenously b.i.d. in combination with 0.5 g metronidazole intravenously t.i.d. (n = 26), or alternatively 2 g cefoxitin intravenously t.i.d. in combination with doxycycline 0.1 g b.i.d. (n = 31). After commencing therapy intravenously, medication with ciprofloxacin, metronidazole and doxycycline was continued orally after two or three days. In the ciprofloxacin/metronidazole group, PID was found to be severe in 7, moderate in 12 and mild in 7 patients. The numbers in the cefoxitin/doxycycline group were 8, 20 and 3 respectively. The clinical result after treatment with ciprofloxacin/metronidazole was resolution of all symptoms in 24 patients and improvement in 2 others. In the cefoxitin/doxycycline treated group, resolution was found in 27 patients, improvement in 2 others. Failure occurred in 2 patients. 53 different microorganisms as the suspected cause of PID were isolated in the ciprofloxacin/metronidazole group and 56 in the cefoxitin/doxycycline group. According to our clinical and bacteriological criteria, treatment for PID was successful in 97% of the ciprofloxacin/metronidazole group and in 87% of the cefoxitin/doxycycline group. Adverse reactions were found in 4 patients in the ciprofloxacin/metronidazole treated group. Therapy had to be terminated in 3 of these patients. In the cefoxitin/doxycycline group 2 patients had adverse reactions, and therapy had to be terminated in one of these patients. According to our results, both antibiotic regimens can be recommended for the treatment of PID.

A comparison of ampicillin/sulbactam and cefoxitin in the treatment of bacterial skin and skin-structure infections.

Seventy-six hospitalized patients with complicated skin/soft-tissue infections were enrolled in this randomized, prospective, third-party-blinded, comparative study of the effectiveness and safety of intravenous or intramuscular administration of ampicillin/sulbactam (1.0 to 2.0 g ampicillin plus 0.5 to 1.0 g sulbactam every 6 hours) and cefoxitin (1.0 to 2.0 g every 6 hours). Twenty-five of 36 ampicillin/sulbactam patients and 33 of 39 cefoxitin patients were evaluable. Clinical and bacteriologic effectiveness did not differ significantly between the two treatment groups (P = .674, P = .118, respectively); neither did duration of hospitalization (P = .894). Twenty-one (84%) ampicillin/sulbactam patients were cured, 2 (8%) were improved, and 2 (8%) were treatment failures. Twenty-eight (85%) cefoxitin patients were cured, 4 (12%) were improved, and 1 (3%) was a treatment failure. All primary pathogens were eradicated in 6 (24%) ampicillin/sulbactam patients; partial eradication occurred in 9 (36%). Primary pathogens were eradicated in 15 (47%) cefoxitin patients and partially eradicated in 8 (25%). Both treatments were well tolerated, with a small number of adverse reactions in each group. The overall incidence of adverse events was similar in the two groups.