Evaluation of the Non-inferiority of Cefoxitin Versus Imipenem/Cilastatin in the Treatment of Urinary Tract Infections Caused by ESBL-producing Escherichia Coli

• Status: Terminated
• Trial end date: 2017-12-01

Summary

Background Information: Infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are becoming increasingly common owing to incorrect use of antibiotics and cross-transmission in healthcare establishments. These give rise to major problems in standard clinical practice: penicillins and cephalosporins cannot be used, and resistance to the other classes of antibiotics normally used, such as fluoroquinolones or cotrimoxazole, is very frequently observed. The current therapeutic strategy involves the use of a carbapenem, which represents the last effective solution on an individual level. However, the growing use thereof is contributing, collectively, to the development of resistance due to the production of carbapenemases, which will become a major public health problem, with a potential therapeutic dead-end. This observation is particularly worrying due to the very small number of antibiotic agents currently in development.

Infectious disease specialists and microbiologists are thus examining alternative agents to carbapenems in the management of infections caused by ESBL-producing E. coli. One of the avenues which could be developed is the use of known agents, already on the market, which are active in vitro on ESBL-producing E. coli, but which are not currently recommended for this indication in standard practice due to the lack of conclusive studies. Cefoxitin, an antibiotic belonging to the cephamycin group, could thus represent an alternative of particular interest in the treatment of infections caused by ESBL-producing E. coli, and help limit the use of carbapenems.

The implementation of a prospective, randomized, non-inferiority study on ertapenem and cefoxitin is of the most interest from a methodological perspective. It will enable recommendations to be drawn up, with a high level of evidence, very long-awaited in the field.

Primary objective: To evaluate the bacteriological non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin.

Secondary objectives:

• To evaluate the clinical non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin.

• To evaluate the impact of cefoxitin and imipenem on the emergence of multiresistant bacteria in the gut flora.

• Phase: Phase 4

Details

• Lead Sponsor: Central Hospital, Nancy, France
• Treatments: Cefotaxime; Cefoxitin; Cilastatin; Imipenem