Impact of ceftriaxone and temocillin on fecal abundance of extended-spectrum β-lactamase producing Escherichia coli in a mouse model

Background Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice. Methods Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E . coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E . coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E . coli isolates with different temocillin minimum inhibitory concentrations. Results Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E . coli . In contrast, temocillin had no effect or transiently decreased the number of 3GCR E . coli . Results obtained with the two strains were similar. Conclusion Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E . coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.