Li Qianxue, Bi Xingming, Diao Youjiang, Deng Xuming
Department of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, PR China.
Am J Vet Res. 2007 Aug;68(8):812-5. doi: 10.2460/ajvr.68.8.812.
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.
15 chicken-derived E coli isolates.
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.
In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 microg/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 microg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 microg/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.
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 microg/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.
通过测定突变预防浓度（MPC）来研究从鸡分离得到的大肠杆菌中恩诺沙星耐药性的发展情况，并对选定分离株的gyrA和parC基因的喹诺酮耐药决定区（QRDR）进行测序。
15株鸡源大肠杆菌分离株。
对所有分离株测定恩诺沙星的MPC和最低抑菌浓度（MIC）。比较MPC与推荐用于治疗鸡大肠杆菌感染的恩诺沙星剂量所达到的最大血清药物浓度。还测定了gyrA和parC的突变频率及QRDR序列变化。
在15株大肠杆菌菌株中，2株的MPC较低（0.016和0.062μg/mL），MPC:MIC比值为2和4，GyrA和ParC蛋白无突变。在9株有GyrA点突变的敏感分离株中，MPC范围为2至16μg/mL。对于GyrA有双突变和ParC有单突变的分离株，MPC>32μg/mL（比鸡体内恩诺沙星的最大血浆浓度高几倍）；与单突变分离株相比，突变频率也低得多。
对于鸡的大肠杆菌感染，MPC似乎有助于确定恩诺沙星给药策略。尽管某些野生型gyrA大肠杆菌分离株对恩诺沙星敏感（MIC为0.125至1μg/mL），但高MPC:MIC比值可能导致感染这些分离株的鸡的恩诺沙星治疗失败。对于涉及高MPC分离株的感染，尤其是那些gyrA和parC基因有突变的分离株，应采用联合抗菌药物治疗。
