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Mutant-prevention concentrations of enrofloxacin for Escherichia coli isolates from chickens

Qianxue LiDepartment of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, PR China
Military Veterinary Institute, Academy of Military Medicine, Changchun, 130062, PR China

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Xingming BiDepartment of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, PR China

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Youjiang DiaoDepartment of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, PR China

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Xuming DengDepartment of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, PR China

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Abstract

Objective—To investigate the development of enrofloxacin resistance among Escherichia coli isolates obtained from chickens by determining mutant-prevention concentrations (MPCs) and sequence the quinolone resistance–determining regions (QRDRs) of gyrA and parC genes in selected isolates.

Sample Population—15 chicken-derived E coli isolates.

Procedures—For all isolates, MPC and minimal inhibition concentration (MIC) of enrofloxacin were determined. The MPCs and maximum serum drug concentrations attained with enrofloxacin doses recommended for treatment of E coli infections in chickens were compared. Mutation frequencies and QRDR sequence changes in gyrA and parC were also determined.

Results—In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 μg/mL), MPC:MIC ratios were 2 and 4, and the GyrA and ParC proteins had no mutations. In 9 susceptible isolates with a GyrA point mutation, MPCs ranged from 2 to 16 μg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 μg/mL (several fold greater than the maximal plasma concentration of enrofloxacin in chickens); mutation frequencies were also much lower, compared with frequencies for single-mutation isolates.

Conclusions and Clinical Relevance—For E coli infections of chickens, MPC appears to be useful for determining enrofloxacin-dosing strategies. The high MPC:MIC ratio may result in enrofloxacin-treatment failure in chickens infected with some wild-type gyrA E coli isolates despite the isolates' enrofloxacin susceptibility (MICs 0.125 to 1 μg/mL). For infections involving isolates with high MPCs, especially those containing mutations in gyrA and parC genes, treatment with combinations of antimicrobials should be adopted.

Abstract

Objective—To investigate the development of enrofloxacin resistance among Escherichia coli isolates obtained from chickens by determining mutant-prevention concentrations (MPCs) and sequence the quinolone resistance–determining regions (QRDRs) of gyrA and parC genes in selected isolates.

Sample Population—15 chicken-derived E coli isolates.

Procedures—For all isolates, MPC and minimal inhibition concentration (MIC) of enrofloxacin were determined. The MPCs and maximum serum drug concentrations attained with enrofloxacin doses recommended for treatment of E coli infections in chickens were compared. Mutation frequencies and QRDR sequence changes in gyrA and parC were also determined.

Results—In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 μg/mL), MPC:MIC ratios were 2 and 4, and the GyrA and ParC proteins had no mutations. In 9 susceptible isolates with a GyrA point mutation, MPCs ranged from 2 to 16 μg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 μg/mL (several fold greater than the maximal plasma concentration of enrofloxacin in chickens); mutation frequencies were also much lower, compared with frequencies for single-mutation isolates.

Conclusions and Clinical Relevance—For E coli infections of chickens, MPC appears to be useful for determining enrofloxacin-dosing strategies. The high MPC:MIC ratio may result in enrofloxacin-treatment failure in chickens infected with some wild-type gyrA E coli isolates despite the isolates' enrofloxacin susceptibility (MICs 0.125 to 1 μg/mL). For infections involving isolates with high MPCs, especially those containing mutations in gyrA and parC genes, treatment with combinations of antimicrobials should be adopted.

Contributor Notes

Supported by the National Natural Science Foundation of China (No. 30671586).

Address correspondence to Dr. Deng.