A high dose and continuous infusion of cefoxitin has been associated with clinical success in treating febrile urinary tract infections (UTIs) in men caused by extended spectrum beta-lactamase–producing (ESBL) Escherichia coli, according to research published in the European Journal of Clinical Microbiology and Infectious Diseases.

Researchers conducted a multicenter, retrospective cohort study to compare the clinical and microbiologic efficacy of cefoxitin with that of carbapenem. Data were collected from 6 French acute care teaching hospitals between January 2013 and June 2015. Included patients were men aged >18 who were treated for with either cefoxitin or carbapenem for ≥50% of the course of antimicrobial therapy. Patients were consecutively enrolled without matching; antibiotic exposure was assessed via data from patient medical records and hospital pharmacies.

In total, data from 66 patients were included: 33 were treated with cefoxitin and 33 were treated with carbapenem. At the end of treatment, 16 patients could not be evaluated; the final cohort included 50 assessable patients (n=23, cefoxitin and n=27, carbapenem). Median follow-up time was 63 days (interquartile range 26-114).

The cohort had a mean age of 66 years ±13 years. The majority of patients (78.4%) had a history of uropathy. The etiology of UTI was community-acquired in 36.4% of patients, nosocomial in 31.8% of patients, and healthcare-associated in 31.8% of patients.

Overall, 28.8% of patients had effective empiric therapy (carbapenem, piperacillin-tazobactam, or aminoglycoside); 25.8% had no empiric therapy, and 45.5% had empiric therapy that was not effective. In the latter 2 groups, 15 patients were treated with cefoxitin and 17 with carbapenem. Baseline characteristics were similar across both treatment groups.

In the carbapenem group, all strains of ESBL E coli demonstrated intermediate response or resistance to cefotaxime and ceftazidime, resistance to fluoroquinolones and trimethoprim/sulfamethoxazole, but were susceptible to carbapenem. In the cefoxitin group, all strains were susceptible to cefoxitin therapy. Median doses of 8000 mg/day of cefoxitin, 3000 mg/day of imipenem, and 1000 mg/day of ertapenem were given to patients. The median duration of effective treatment was 22 and 18 days in the cefoxitin and carbapenem groups, respectively.

Results also demonstrated that a higher dose of cefoxitin (8000mg vs 6000mg) and administration via continuous infusion were significantly associated with clinical success. Further, there was no evidence of emergent resistance to cefoxitin, and 614 days of treatment with carbapenem were spared.

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Investigators observed clinical success in 73.9% and 81.5% of patients in the cefoxitin and carbapenem groups, respectively, and microbiologic success in 57.9% and 50% of patients, respectively. In univariate and multivariable analyses, no significant difference was noted for clinical or microbiologic success between the groups (odds ratio 0.90 and 0.85, respectively). In the cefoxitin group, both a higher dose of medication and continuous infusion were significantly associated with clinical success.

Study limitations included those inherent to the retrospective nature of the study, such as residual confounding bias and the small sample size. In addition, the investigators noted that the ecologic effect of cefoxitin is “probably far from negligible” as a result of biliary excretion and antianaerobic activity.

“Our results suggest that cefoxitin therapy is effective [in this patient population], particularly when using high doses and continuous infusion, and can limit the use of carbapenems to avoid spread of resistances,” the researchers concluded. “Larger prospective studies or, ideally, randomized controlled trials are still required to define the exact efficacy of cefoxitin.”

Reference

Senard O, Lafaurie M, Lesprit P, et al. Efficacy of cefoxitin versus carbapenem in febrile male urinary tract infections caused by extended spectrum beta-lactamase–producing Escherichia coli: a multicenter retrospective cohort study with propensity score analysis [published online September 11, 2019]. Eur J Clin Microbiol Infect Dis. doi: 10.1007/s10096-019-03701-0