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.

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.

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.

[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.

[Perioperative use of ampicillin/sulbactam, cefoxitin and piperacillin/ metronidazole in elective colon and rectal surgery. A prospective randomized quality assurance study of 422 patients]. / Perioperative Anwendung von Ampicillin/Sulbactam, Cefoxitin und Piperacillin/Metronidazol in der elektiven Colon- und Rectumchirurgie. Eine prospektive randomisierte Qualitätssicherungsstudie bei 422 Patienten.

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.

Prospective alterations in therapy for penetrating abdominal trauma.

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.

Comparative study of single-dose cefotaxime and multiple doses of cefoxitin and cefazolin as prophylaxis in gynecologic surgery.

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.

Detection of antibiotic-induced platelet dysfunction in whole blood using flow cytometry.

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%.

Therapeutic interchange of ampicillin-sulbactam for cefoxitin.

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.

A comparative evaluation of the safety and efficacy of cefotetan and cefoxitin in surgical prophylaxis.

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.

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

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

Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery.

One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for the prevention of postoperative wound infection. Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation. Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery. For operations that exceeded 2-4 h duration an additional dose of each agent was administered. Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation. Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%). The operative site infection rate was 6.5% for cefmetazole and 7.7% for cefoxitin (P greater than 0.05). Serious drug related adverse effects were not observed. This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations.

Cefmetazole versus cefoxitin in prevention of infections after abdominal surgery.

Patients undergoing elective abdominal surgery were randomized to receive cefmetazole or cefoxitin in a three-dose perioperative prophylactic regimen. There were three infections in 89 evaluable patients receiving cefmetazole. There were six infections in 39 patients receiving cefoxitin. Both regimens were acceptable with minimal toxicity.

Comparative efficacy and safety of cefmetazole or cefoxitin in the prevention of postoperative infection following vaginal and abdominal hysterectomy.

We evaluated three 1-g doses of cefmetazole in comparison with the standard three 2-g doses of cefoxitin for prophylaxis in vaginal or abdominal hysterectomy to determine efficacy and safety. The antibiotics were administered intravenously 30-90 min before the incision and were followed with additional intravenous doses 8 and 16 h or 6 and 12 h later, respectively. The patients received povidone-iodine vaginal preparations before surgery; vaginal packs, when used, contained no antibiotic agents. Vaginal cultures were obtained before the vaginal preparation, at the time of discharge from hospital and when there was a suggestion of operative site infection. The activity of both antibiotics against these organisms was tested. Patient demographic characteristics and surgical procedures were similar in each treatment group. The difference between the primary failure rates with the two antibiotics (2 of 35 (5.7%) with cefmetazole and 2 of 16 (12.5%) with cefoxitin) did not reach statistical significance, and results were similar for the two routes of hysterectomy. Cefmetazole was more active than cefoxitin against the majority of the aerobic and anaerobic organisms recovered, although approximately 20-30% of the isolates showed resistance, or intermediate sensitivity, generally to both antibiotics.