Stopped: Not enought inclusion
Escherichia coli is the primary cause of urinary tract infections and Gram-negative bacteremia worldwide. Since the early years of the 21st century, E.coli has acquired a new mechanism of resistance to antibiotics: extended spectrum β-lactamase (ESBL), type CTX-M. These ESBL inactivate most β-lactams, the preferred class of antibiotics for the treatment of severe E.coli infections. Moreover, the strains that produce these ESBL are often resistant to other classes of antibiotics. Their rapid spread constitutes a major public health concern because of a serious risk of therapeutic impasse. Treatment options in cases of infection with ESBL-producing E.coli are often limited to carbapenems, a class of more recently developed β-lactams. Carbapenems have a very wide spectrum of activity but their effectiveness is threatened by the emergence of strains producing carbapenemases. The development of therapeutic alternatives to treat ESBL-producing E.coli infections is therefore essential. Cephamycins, including cefoxitin, are β-lactams marketed in the seventies but their use was practically abandoned when wide spectrum antibiotics became available. They are distinguished by the presence of an α-methoxy group in position 7 which interferes with the action of the extended-spectrum β-lactamase and renders it ineffective against cephamycins. Cefoxitin is therefore active in vitro against ESBL-producing E.coli and offers the advantage of a narrower antibacterial spectrum, thus reducing the selection pressure and the emergence of resistance. However, the in vivo activity of cefoxitin for the treatment of ESBL-producing E.coli infections has never been measured. Furthermore, available pharmacokinetic and pharmacodynamic (PK/PD) data for cefoxitin are dated and incomplete, which raises many questions concerning the optimal dosage regimen. We have shown in a mouse model of ESBL-producing E. coli CTX-M pyelonephritis that cefoxitin efficacy is comparable to that of carbapenems without selecting resistant mutants. Cefoxitin could thus constitute an alternative to carbapenems for the treatment of pyelonephritis caused by ESBL-producing E.coli.
Age range
18 Years
Sex
FEMALE
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The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
To assess Clinical and microbiological response
Timeframe: 10 days