Shimizu Takae, Harada Kazuki, Kataoka Yasushi
Acta Vet Scand. 2013 May 1;55(1):37. doi: 10.1186/1751-0147-55-37.
The mutant prevention concentration (MPC) is an important parameter to evaluate the likelihood of growth of fluoroquinolone-resistant mutants for antimicrobial-pathogen combinations. The MPCs of fluoroquinolones for different canine pathogens have not been compared. In this study, we compared for the first time orbifloxacin MPCs between susceptible strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus pseudintermedius of canine origin.
More than 1010 CFU/ml of 10 strains of each bacterial species were inoculated onto Muller-Hinton agar supplemented with different concentrations of orbifloxacin from 1× to 64× minimum inhibitory concentration (MIC) and the MPCs were recorded. MICs of original strains and of mutants arising after exposure to sub-MPC concentrations (one per original strain) were determined in the presence or absence of efflux pump inhibitors (EPIs). The effects of quinolone resistance-determining region (QRDR) mutations were also examined.
MPCs were significantly higher for P. aeruginosa (16-128 μg/ml) than for E. coli (0.5-32 μg/ml). MPCs for S. pseudintermedius varied between the low-susceptible (16-128 μg/ml) and the high-susceptible strains (4-16 μg/ml) and were the most broadly distributed among the three species. Regarding resistance mechanisms, only one QRDR mutation in gyrA was found in all of the 10 mutants of E. coli and in 4 of the 10 mutants of P. aeruginosa, whereas mutations in both grlA and gyrA were found in 3 mutants and one mutation in grlA was found in 2 mutants among the 10 mutants of S. pseudintermedius. In the presence of an EPI, the MICs of P. aeruginosa mutants decreased markedly, those of E. coli mutants decreased moderately, and those of S. pseudintermedius mutants were unaffected.
MPCs of orbifloxacin vary between bacterial species of canine pathogens, possibly due to the diversity of the main fluoroquinolone resistance mechanism among these species. Therefore, the type of bacterial species should be taken into consideration when using fluoroquinolone drugs such as orbifloxacin in canines.
突变预防浓度（MPC）是评估抗菌药物 - 病原体组合中氟喹诺酮耐药突变体生长可能性的重要参数。尚未比较氟喹诺酮类药物对不同犬类病原体的MPC。在本研究中，我们首次比较了犬源大肠杆菌、铜绿假单胞菌和中间型葡萄球菌敏感菌株之间奥比沙星的MPC。
将每种细菌的10个菌株，超过1010 CFU/ml接种到补充有不同浓度奥比沙星（从1×至64×最低抑菌浓度（MIC））的Muller-Hinton琼脂上，并记录MPC。在有或没有外排泵抑制剂（EPI）的情况下，测定原始菌株以及暴露于亚MPC浓度后产生的突变体（每个原始菌株一个）的MIC。还检查了喹诺酮耐药决定区（QRDR）突变的影响。
铜绿假单胞菌的MPC（16 - 128μg/ml）显著高于大肠杆菌（0.5 - 32μg/ml）。中间型葡萄球菌的MPC在低敏感菌株（16 - 128μg/ml）和高敏感菌株（4 - 16μg/ml）之间变化，并且在这三个物种中分布最广。关于耐药机制，在大肠杆菌的所有10个突变体和铜绿假单胞菌的10个突变体中的4个中仅发现gyrA中的一个QRDR突变，而在中间型葡萄球菌的10个突变体中的3个中发现grlA和gyrA中的突变，在2个突变体中发现grlA中的一个突变。在存在EPI的情况下，铜绿假单胞菌突变体的MIC显著降低，大肠杆菌突变体的MIC适度降低，而中间型葡萄球菌突变体的MIC不受影响。
奥比沙星的MPC在犬类病原体的细菌物种之间有所不同，这可能是由于这些物种中主要氟喹诺酮耐药机制的多样性。因此，在犬类中使用氟喹诺酮类药物如奥比沙星时应考虑细菌物种类型。
