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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/m 2 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/m 2 .

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.

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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

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/β-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.

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., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2010 S. Karger AG, Basel.)

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.

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.

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.

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.

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., (Copyright 2001 S. Karger AG, Basel)

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.

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.

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.

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.

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.

Generalized pustular eruptions with fever present a diagnostic challenge. A history of preceding drug exposure, and rapid disappearance of the eruption after the drug is stopped, suggest a drug-induced aetiology rather than pustular psoriasis. We describe and evaluate the clinical and histological features of four patients who developed a generalized pustular eruption following drug administration. The history of preceding drug exposure and the presence of a variable number of eosinophils in the inflammatory infiltrate in the lesions of these cases suggested that the generalized pustular eruptions were drug-induced.

Clostridium difficile and/or toxin B were isolated from the faeces of 3 (1.6%) of 184 patients within the first two days of hospitalisation in the University of Tübingen, Gynaecological Clinic. With following stool samples from a total of 117 patients the isolation rate of C. difficile was examined in relation to the treatment with antibiotics. From the first group of 61 patients, who had had gynaecological operations and were not treated with any antibiotic, the isolation rate of C. difficile rose statistically but not significantly from 0% at the time of admission up to 3.3% during hospitalisation. Amongst the second group of 17 patients, who had had gynaecological operations and were treated with various antibiotics for at least three days, the isolation rate was also found to rise insignificantly from 0 to 11.8% (p < 0.1). The third group of 33 patients, who had had gynaecological operations and perioperative prophylaxis with cefoxitin (one to three doses 2 g each), the isolation rate rose significantly from 0 to 12.1% (p < 0.05). The result of this study shows that the bacterial flora of the gut was probably altered even after a very brief application of cefoxitin. In two environmental examinations on the wards of the patients of this study, C. difficile was not isolated in any case.

As has been proved before, antibiotic prophylaxis is highly effective in lowering wound infection rates in colorectal surgery. In order to establish quality control, we checked the effectiveness of three different prophylactic antibiotic regimes in 422 patients in a prospective and randomized trial. Between the three groups were no significant differences as regards age, type of operation and risk factors like adipositas and diabetes. The wound infection rate according to CDC-criteria was from 7.0 to 9.5%. We did not find a significant difference between the three antibiotic regimes. It is therefore our conclusion, that in our setting each of the three different types of antibiotics is of equal value. This means, on the other hand, that the cheapest one is enough.

A multicenter randomized comparative trial was done to assess the safety and efficacy of oral ofloxacin (400 mg twice daily for 10 days) versus cefoxitin (2 g intramuscularly) followed by doxycycline (100 mg twice daily orally for 10 days) for the outpatient treatment of uncomplicated pelvic inflammatory disease (PID). Neisseria gonorrhoeae (GC) grew on pretreatment endocervical cultures from 43 of 268 women (16%), and in 30 of 247 women (12%) cultures were positive for Chlamydia trachomatis (Ct). Ninety-five percent (122/128) of the women treated with the ofloxacin regimen and 93% (112/121) of those treated with the cefoxitin/doxycycline regimen had cure or improvement on examination at a minimum of one follow-up visit. All GC species were eradicated by both ofloxacin and cefoxitin. Among women who returned for follow-up, the eradication of C trachomatis was 88% (15/17) for the cefoxitin/doxycycline group and 100% (18/18) for ofloxacin. Side effects were more prevalent in the cefoxitin/doxycycline group (15%) than in the ofloxacin group (7%), nausea/vomiting being the most frequent adverse effect. In this study, it appears that ofloxacin and cefoxitin/doxycycline have similar clinical effectiveness for the outpatient treatment of uncomplicated pelvic inflammatory disease.

In a double-blind, randomized study, 170 patients with traumatic perforation of the gastrointestinal tract were administered an advanced-generation cephalosporin. Patients were divided into infection risk groups (< or = 40%, low; 40% to 70%, mid; and > 70%, high) at surgical closure using a logistic regression formula based on four proved risk factors--age, blood replacement, ostomy, and the number of organs injured. Patients in the low group received 2 days of antibiotic therapy; those in the mid to high group received 5 days of antibiotic therapy. Those patients in the low to mid group had primary wound closure; those in the high group had their wounds packed open and closed later. Most of the patients (144 [85%]) were in the low group. Their major and minor infection rates (10% and 12%, respectively) were not significantly different from 145 historic control subjects receiving 5 days of antibiotic therapy (9% major; 14% minor). Patients in the mid to high group showed a greater incidence of major infections (46%) but a similar incidence of minor infections (12%). The results indicate that risk factors can be used to identify low-risk patients who require only short-term antibiotic therapy and primary wound closure. The remaining patients are at greater risk for infection despite prolonged antibiotic therapy and delayed wound closure.

In this comparative, randomized, multicenter trial, 273 patients scheduled for gynecologic surgery were studied: 87 received a single 1-g dose of cefotaxime 30 minutes before surgery; 81 were given a 1-g dose of cefoxitin 30 minutes before surgery and 1 g every 6 hours for 24 hours after surgery (total dose 4 g); and 105 received a 1-g dose of cefazolin 30 minutes before surgery, followed by 1 g every 8 hours for 48 hours (total dose 6 g). Patients who received cefotaxime had a significantly lower incidence of postoperative fever compared with those treated with cefoxitin or cefazolin (p < 0.01). The incidence of positive urinary cultures was lower in the cefotaxime and cefazolin groups when compared with the cefoxitin group (p < 0.01 and p < 0.05, respectively). The results of this study confirm the efficacy of cefotaxime as prophylaxis in surgical infections and demonstrate that single-dose cefotaxime is more effective than a four-dose regimen of cefoxitin.

Objective: The hypothesis of the study is that cefotetan and cefoxitin will be equally efficacious and safe in the treatment of post-cesarean section endometritis., Study Design: In a double-blind, randomized manner 140 patients with post-cesarean section endometritis were treated with cefotetan, 2 gm intravenously every 12 hours, or cefoxitin, 2 gm intravenously every 6 hours. They were followed prospectively for clinical response and side effects. Cure rates between the two groups were compared with the chi 2 test., Results: The cure rates were 83% for cefotetan and 79% for cefoxitin (p = 0.56). No patient required a change in therapy due to adverse effects, and no abnormal bleeding occurred., Conclusion: In this study cefotetan and cefoxitin appeared equally effective in treating endometritis with no difference in side effects or complications.

In a randomized, prospective study, single-drug antibiotic therapy with cefoxitin (CFX) was compared to combination therapy with gentamicin and clindamycin (G/C) as definitive treatment for acute colonic diverticulitis. Excluding individuals requiring immediate operation, 51 patients with a clinical diagnosis of diverticulitis, who were hospitalized at five different medical centers, were randomized to receive CFX (30 patients) or G/C (21 patients). Age, sex, and the severity of diverticulitis were similar in the two groups. The cure rates of 90% and 85.7% observed for CFX and G/C, respectively, did not differ significantly. Leukocytosis resolved in a shorter time period in patients treated with CFX than in those treated with G/C (2.5 +/- 0.4 vs 4.1 +/- 0.6 days, respectively) (P = 0.03, Student's t test, unpaired data). Two cases of possibly antibiotic-related toxicity occurred in the CFX group versus three cases in the G/C group. The average cost of a course of CFX therapy was $417 compared with $488 for G/C. In this study, cefoxitin demonstrated efficacy and tolerability similar to that of gentamicin-clindamycin in the treatment of acute colonic diverticulitis and may be preferred in view of its narrower antimicrobial spectrum and lower cost.

Using flow cytometry and activation-dependent monoclonal antibodies, we have developed a technique based on forward angle-light scatter (FALS) and immunofluorescence that simultaneously detects human platelet activation, secretion, and aggregation in whole blood. To detect the effects of cefotetan and latamoxef, both of which contain an N-MTT side chain, and of free N-MTT and cefoxitin, which does not contain the N-MTT side chain, on platelet activation and secretion, platelets were stained by the indirect method using a murine-produced platelet specific activation-dependent monoclonal antibody, S12, and a goat anti-mouse IgG fluorescein-conjugated antibody. S12 binds to a 140kd alpha granule membrane protein (GMP-140) that is expressed during secretion. Single parameter, 256 channel, log integrated green fluorescence histograms were generated, and negative and positive fluorescent populations were defined. Latamoxef and cefotetan reduced the number of platelets expressing S12 by more than 43%. In contrast, cefoxitin reduced the number of platelets expressing S12 by only 13.5%. The inhibition of GMP-140 expression per platelet was calculated by converting the log data to linear fluorescence intensity. Latamoxef and cefotetan inhibited expression of GMP-140 by 88% and 87% respectively. Free N-MTT inhibited its expression by 68%. In contrast cefoxitin reduced GMP-140 expression per platelet by only 45%.

A therapeutic interchange program based on microbial patterns within an institution is described. A change in anaerobic susceptibility patterns, increased prevalence of enterococcal infections, and cost factors provided the rationale for the therapeutic interchange of ampicillin-sulbactam for cefoxitin. Ampicillin-sulbactam was recommended for prophylaxis in intraabdominal or gynecological surgery as well as for treatment for gynecological infections. Cefoxitin was restricted to penicillin-allergic patients and women who were pregnant or breast-feeding. The transition from cefoxitin to ampicillin-sulbactam proceeded smoothly as a result of preliminary education of pharmacists and physicians. Pharmacists participated in continuing-education programs and received concise guidelines for the interchange and follow-up instructions; physicians learned of the program from the drug newsletter published by the pharmacy department. Three months after the program began, only one physician was resistant to the interchange. After the program began, 11 antimicrobials, including cefoxitin, were used less frequently and ampicillin-sulbactam use increased. No adverse clinical consequences from the interchange were detected. A therapeutic interchange program based on institution-specific microbial patterns and educational efforts by the pharmacy department produced a change in physician prescribing.

Use of decision analysis in the formulary evaluation of the second-generation cephamycin derivatives cefoxitin, cefotetan, and cefmetazole is described. The rating system used was adapted from one used for the third-generation cephalosporins. Data on spectrum of activity, pharmacokinetics, adverse reactions, cost, and stability were taken from the published literature and the FDA-approved product labeling. The weighting scheme used for the third-generation cephalosporins was altered somewhat to reflect the more important aspects of the cephamycin derivatives and their potential role in surgical prophylaxis. Sensitivity analysis was done to assess the variability of the final scores when the assigned weights were varied within a reasonable range. Scores for cefmetazole and cefotetan were similar and did not differ significantly after sensitivity analysis. Cefoxitin scored significantly lower than the other two drugs. In the absence of data suggesting that the N-methyl thiotetrazole side chains of cefmetazole and cefotetan cause substantial toxicity, these two drugs can be considered the most cost-efficient members of the second-generation cephamycins.

Ampicillin-sulbactam (750 mg) given orally twice daily for 10 days was evaluated for the treatment of acute pelvic inflammatory disease (PID) in an ambulatory setting in Nairobi, Kenya. The first 26 women received ampicillin-sulbactam in an open-label fashion, and the remaining 75 women were randomly selected to receive either ampicillin-sulbactam (n = 38) or cefoxitin (2 g) intramuscularly and probenecid (1 g) orally, followed by doxycycline (100 mg) orally twice daily for 10 days (n = 37). Women were enrolled in a sexually transmitted disease clinic and were followed for clinical and microbiologic responses at 1 to 2 weeks and 4 to 6 weeks posttreatment. Women had a later follow-up visit to note interim pregnancy or underwent hysterosalpingography for fertility outcome assessment. The short-term clinical response rates were 70% for ampicillin-sulbactam and 72% for cefoxitin-doxycycline (P = 0.47). Among Chlamydia trachomatis-infected women treated with ampicillin-sulbactam, three had microbiologic relapse. The post-PID tubal obstruction rates were similar in the two groups: 18% for ampicillin-sulbactam and 33% for cefoxitin-doxycycline (P = 0.31). Neither regimen was highly effective as a therapy for acute PID. These data strongly argue that primary prevention must be the goal for a reduction of PID morbidity and show that improved therapy for the treatment of PID in the ambulatory setting is needed.

The object of this randomized study was to compare the safety and efficacy of oral ofloxacin, 400 mg twice daily for 10 days, versus intramuscular cefoxitin, 2 gm, plus oral probenecid, 1 gm, followed by oral doxycycline, 100 mg twice daily for 10 days, in the outpatient treatment of uncomplicated acute salpingitis. Thirty-eight women (53%) had Neisseria gonorrhoeae from their pretreatment endocervical or endometrial cultures, and 18 had Chlamydia trachomatis (25%). Thirty-five of 37 women (95%) treated with the ofloxacin regimen were clinically cured, and 34 of 35 (97%) were cured with the cefoxitin-doxycycline regimen (p = 0.52). One clinical failure occurred in each group with N. gonorrhoeae infection, and one failure occurred in the ofloxacin group because of side effects. The bacteriologic response for N. gonorrhoeae in both groups was 100%. The eradication of C. trachomatis was 100% (10/10) for the cefoxitin/doxycycline group and 86% (6/7) for ofloxacin. The side effects were similar in both groups of subjects. In this study both regimens were effective for the outpatient treatment of uncomplicated acute salpingitis.

Safety and efficacy were evaluated and compared retrospectively in 77 patients who received cefotetan (CTN) and 51 patients who received cefoxitin (CFX) for surgical prophylaxis. Both groups were similar with respect to age and gender. Surgical procedures were similar between groups (e.g., obstetric/gynecologic, renal transplant, colon, exploratory laparotomy, gastroduodenal, hernia repair). Postoperative infectious complications were more common in the CTN group (11.6 percent [9/77]) than in the CFX (7.8 percent [4/51]) group; however, this difference was not statistically significant. A higher incidence of wound infections was noted in the CTN group (5.2 percent [4/77]) than in the CFX group (2.0 percent [1/51]); this difference was also not significant. Patients receiving immunosuppressive therapy were more likely to develop infectious complications when CTN was used for prophylaxis (p = 0.0001). Clinically significant blood loss was not noted during surgery. Elevations in prothrombin times (greater than 1 sec) occurred in 27.3 percent (3/11) of CTN and 11.1 percent (1/9) of CFX patients (not significant). Except for the small subset of patients receiving concomitant immunosuppressive therapy, CTN appeared to be as safe and effective as CFX when used for surgical prophylaxis. Although not statistically significant, the increased incidence of wound infections in the CTN-treated patients requires further study in a prospective randomized comparison.

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.

The identification of pathogens and the early recognition of pelvic infections in patients after hysterectomy, cesarean delivery and vaginal delivery were analyzed. Criteria for administering cephamycin therapy were established, as were guidelines for evaluating the progress of the infection. In a comparative study of the safety and efficacy of cefmetazole and cefoxitin in 145 hospitalized patients with pelvic infections there were no significant differences between either the bacteriologic or clinical cure rates of the two antibiotics. Both were efficacious and safe for the treatment of obstetric-gynecologic soft tissue infections.

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.

Human serum sickness is a syndrome characterized by fever, malaise, skin rashes, arthralgias, gastrointestinal disturbances, and lymphadenopathy. It is believed to be mediated by circulating immune complexes composed of a foreign antigen and host antibody. Several cephalosporins have been associated with serum sickness. We report the occurrence of serum sickness in a patient who received cefoxitin, a commonly used cephamycin antibiotic, and pentoxifylline, a xanthine derivative that improves the flow properties of blood by decreasing its viscosity. Serum sickness has not been previously reported with the use of cefoxitin or pentoxifylline.

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indole-producing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

A total of 19 patients who had local or systemic infections with a variety of difficult-to-treat blood disorders were treated with cefoxitin (CFX). The following findings were obtained. 1. Fifteen out of 19 patients' responses were judged "excellent" or "good" with an overall cure rate of 78.9%. 2. As to the side effects of CFX, transient elevations in S-GOT, S-GPT were observed in 3 patients, urine protein in 2 patients, and hematuria in 1 patient. However, these abnormalities cannot be solely attributed to CFX because these patients were treated with either antitumor agents or aminoglycosides, and some had undergone blood transfusions. 3. CFX should be considered for the treatment of severe infections because it is well tolerated, has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative pathogens and is highly resistant to beta-lactamases.

This clinical trial was designed to evaluate the efficacy, safety and patient tolerance of cefoxitin (CFS) in 46 patients who were admitted to the hospitals from June 1983 to April 1984. The daily doses of CFX for 34 patients (ages ranged from 6 to 75 years old) were 2 to 8 g to prevent the infections and for 12 patients (ages ranged from 55 to 81 years old) were 2 to 6 g to treat the infections by intravenous drip infusion 1 or 3 times a day in divided doses. The following results were obtained. All of 34 patients with intracranial operation who received CFX for prevention of postoperative infections showed good results. Of 12 patients with postoperative pneumonia, infections of urinary tract and late meningitis, 11 patients showed good results. One patient was discontinued on the 3 days because of the drug eruption which improved 3 days after. The side effect was noted in only 1 patient. This was eruption which improved 3 days after the stop of the administration. The influences to the laboratory data due to CFX were not recognized. The results of this study demonstrated that CFX was an excellent drug for the prevention and treatment of the postoperative infections in the neurosurgical field because of high efficacy rate and safety.

Using a new cephamycin antibiotic, cefoxitin, clinical studies were carried out, and the following results were obtained: (1) Cefoxitin was administered to 52 children with 38 respiratory tract infections, 2 urinary tract infections, 1 acute otitis media and others, who ranged in age from 2 months to 11 years old. (2) Cefoxitin was given intravenously at a daily dose of 27.3 mg/kg to 110.5 mg/kg. (3) The overall efficacy rate was 80% in 46 cases, i.e., excellent in 10, good in 27, fair in 7 and poor in 2. (4) Clinical side effects were not seen except exanthema in 1 patient. Elevation of GOT and GPT was seen in 2 patients, elevation of A1-P in 1 and eosinophilia in 2 by laboratory tests. However, these findings were alleviated rapidly following the cessation of therapy.

Since the introduction of cephalothin and cephaloridine as the first parenteral cephalosporins and cephalexin as the first member of the group which is absorbed from the gastrointestinal tract, several new cephalosporin derivatives have been developed. Most of these have no major advantages over cephalothin, cephaloridine or cephalexin. Increased knowledge about the importance of beta-lactamases for bacterial resistance against beta-lactam antibiotics has focused interest on development of drugs with increased resistance to degradation by these enzymes. Among the caphalosporins, cefamandole and cefuroxime have been found to be markedly more active against beta-lactamase producing Gram-negative bacteria. A new group of beta-lactam antibiotics, the cephamycins, have been introduced with cefoxitin as the first clinically useful member. Cefoxitin has the spectrum of a beta-lactamase-resistant cephalosporin and is also active against Bacteroides fragilis. The review concentrates on the antibacterial spectrum of these three new antibiotics and on their clinical efficacy.

A total of 20 hospitalized patients underwent orthopedic surgery in the Tokyo Metropolitan Police Hospital during the period from December 1981 to March 1982. These patients were treated with cefoxitin, mainly, for the prevention of postoperative infections. The following clinical findings were obtained. 1. Out of the 20 patients, 14 were judged 'good' and 6 'fair'. 2. No side effects were reported by the patients or were evident in the clinical data. 3. These clinical results indicated that cefoxitin is a very effective antibiotic for the prevention of postoperative infections in orthopedic surgery.