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Experimental Therapeutics

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
Maleck V. Vasseur
aINRA, UMR1331 TOXALIM, Toulouse, France
bUniversité de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France
cAnses, Laboratoire de Fougères, Fougères, France
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Michel Laurentie
cAnses, Laboratoire de Fougères, Fougères, France
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Jean-Guy Rolland
cAnses, Laboratoire de Fougères, Fougères, France
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Agnès Perrin-Guyomard
cAnses, Laboratoire de Fougères, Fougères, France
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Jérôme Henri
cAnses, Laboratoire de Fougères, Fougères, France
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Aude A. Ferran
aINRA, UMR1331 TOXALIM, Toulouse, France
bUniversité de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France
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Pierre-Louis Toutain
aINRA, UMR1331 TOXALIM, Toulouse, France
bUniversité de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France
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Alain Bousquet-Mélou
aINRA, UMR1331 TOXALIM, Toulouse, France
bUniversité de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France
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DOI: 10.1128/AAC.02135-13
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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 (105 CFU) or a high (109 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.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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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
Maleck V. Vasseur, Michel Laurentie, Jean-Guy Rolland, Agnès Perrin-Guyomard, Jérôme Henri, Aude A. Ferran, Pierre-Louis Toutain, Alain Bousquet-Mélou
Antimicrobial Agents and Chemotherapy Feb 2014, 58 (3) 1744-1748; DOI: 10.1128/AAC.02135-13

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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
Maleck V. Vasseur, Michel Laurentie, Jean-Guy Rolland, Agnès Perrin-Guyomard, Jérôme Henri, Aude A. Ferran, Pierre-Louis Toutain, Alain Bousquet-Mélou
Antimicrobial Agents and Chemotherapy Feb 2014, 58 (3) 1744-1748; DOI: 10.1128/AAC.02135-13
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