Abstract

Abstract Background Carbapenems are regarded as first-line agents for the treatment of ESBL-producing bacterial infections, even when in vitro activity to other beta lactams is demonstrated. However, overuse is associated with the selection of beta-lactamases that can hydrolyze carbapenems. Patients with isolated urinary tract infections due to ESBL–producing E. coli potentially have a lower burden of infection ("low inoculum"). These patients are frequently less ill and may benefit from non-carbapenem therapy. Cephamycins have in vitro activity against ESBL–producing Enterobacterales, and may be useful in the treatment of ESBL E. coli urinary tract infections as a carbapenem sparing agent. Methods Patients 18 years of age and older, hemodynamically stable with negative blood cultures and who demonstrated signs and symptoms of a urinary tract infection with a urine culture showing ESBL E. coli, were eligible to participate. Patients were started on initial antimicrobial therapy at the discretion of the admitting physician, and if the urine culture showed ESBL E. coli with an MIC of less than 8, the antimicrobial stewardship team requested to switch the patient to Cefoxitin 2 g intravenously every 6 hours, via extended infusion. The dose was renally adjusted as appropriate, and patients with beta-lactam allergies were excluded. Results 46 patients were evaluated between May 2017-April 2022. Patients received antibiotics for 2.6+1 day before the switch to Cefoxitin. The mean duration of therapy with Cefoxitin was 4.5+2.2 days. All 46 patients had resolution of fever and dysuria. Six patients were readmitted within 30 days, but none were due to a urinary tract infection. 30 patients had a repeat urinalysis at 48 hours, and all demonstrated reduction in pyuria. 39 patients had a repeat urine culture following completion of therapy, and 36 had converted to culture-negative status. Conclusion Cefoxitin is a useful agent for the treatment of ESBL E. coli urinary tract infections. The optimal dose appears to be 2 g intravenously every 6 hours, via extended infusion, in patients with normal creatinine clearance. Further larger studies, involving patients with pyelonephritis, are needed to validate these findings. Disclosures Ramesh V. Nathan, MD, Eli Lilly: Grant/Research Support|PPD: Grant/Research Support.

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