Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

Maleck V Vasseur; Michel Laurentie; Jean-Guy Rolland; Agnès Perrin-Guyomard; Jérôme Henri; Aude A Ferran; Pierre-Louis Toutain; Alain Bousquet-Mélou

Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

Maleck V Vasseur Michel Laurentie ¹ Jean-Guy Rolland ¹ Agnès Perrin-Guyomard ¹ Jérôme Henri ¹ Aude A Ferran ² Pierre-Louis Toutain ² Alain Bousquet-Mélou ^{2, *}

* Corresponding author

1 ANSES - ANSES - Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail

2 Physiologie et Toxicologie Expérimentales

Abstract : The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10(5) CFU) or a high (10(9) CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals.

Mots-clés : cefquinome klebsiella pneumoniae résistance antibiotique antibiotic resistance flore feces fecal flora

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Pharmaceutical sciences / Medication

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https://hal-anses.archives-ouvertes.fr/hal-00978511
Contributor : Emmanuelle Chiffoleau <>
Submitted on : Monday, April 14, 2014 - 12:09:51 PM
Last modification on : Friday, June 14, 2019 - 6:21:09 PM

Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

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Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

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