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.
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Authors | Maleck V Vasseur, Michel Laurentie, Jean-Guy Rolland, Agnès Perrin-Guyomard, Jérôme Henri, Aude A Ferran, Pierre-Louis Toutain, Alain Bousquet-Mélou |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 58
Issue 3
Pg. 1744-8
( 2014)
ISSN: 1098-6596 [Electronic] United States |
PMID | 24395228
(Publication Type: Journal Article)
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Chemical References |
- Anti-Bacterial Agents
- Cephalosporins
- cefquinome
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Topics |
- Animals
- Anti-Bacterial Agents
(administration & dosage, pharmacology, therapeutic use)
- Bacterial Load
- Cephalosporins
(administration & dosage, pharmacology, therapeutic use)
- Drug Resistance, Bacterial
(drug effects)
- Feces
(microbiology)
- Klebsiella Infections
(drug therapy)
- Klebsiella pneumoniae
(drug effects)
- Male
- Pneumonia, Bacterial
(drug therapy)
- Rats
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