Mutant prevention concentration of orbifloxacin: comparison between Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus pseudintermedius of canine origin

Abstract

BackgroundThe 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.MethodsMore 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.ResultsMPCs 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.ConclusionsMPCs 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.

Pharmacokinetics, milk penetration and PK/PD analysis by Monte Carlo simulation of marbofloxacin, after intravenous and intramuscular administration to lactating goats

“…Based on MIC values, the fact that MIC 90 /MIC 50 and MIC 99 /MIC 90 ratios were approximately 2 and that all strains were susceptible to MFX, there is no evidence of clinically relevant emergence of resistance in the studied CNS strains. MPC/MIC ratios ranged from 2–32 and for CNS strains, with a MPC 90 /MIC 90 =16, similar to those reported in other studies for quinolones (Allen, Kaatz, & Rybak, ; Awji et al., ; Shimizu et al., ). In this study, heterogeneity of MPCs was observed in strains with similar MICs.…”

“…This finding was reported by Shimizu et al. () for Staphylococcus pseudointermedius strains with high and low susceptibility to orbifloxacin.…”

“…(), Gebru, Choi, Lee, Damte, and Park (), Gebru et al. (), Shimizu, Harada, and Kataoka () and Firsov et al. ().…”

Effects of oral orbifloxacin on fecal coliforms in healthy cats: a pilot study

“…In general, the concept of a mutant selection window has considerable implications for the acquisition of FQ resistance, and antimicrobials at concentrations beyond the mutant prevention concentration (MPC) can prevent the development of FQ-resistant mutants [ 5 ]. In our study, the fecal ORB concentration in cats treated with the doses of 2.5 and 5.0 mg/kg far exceeds the MPC value of E. coli (0.5–32 µ g/m l ); this result has been confirmed by another study [ 26 ]. These findings suggest that oral ORB poses a low risk of selection of highly FQ-resistant mutants among fecal E. coli isolates in cats because of high gut levels.…”

Comparative Study of the Mutant Prevention Concentrations of Sulfamethoxazole-Trimethoprim Alone and in Combination with Levofloxacin against <i>Stenotrophomonas maltophilia</i>

“…The lower boundary of the range is the minimum inhibitory concentration (MIC) and the upper is the mutant prevention concentration (MPC) [6] [7] [8]. This concept and hypothesis have been used to study a variety of bacteria to achieve slowing the amplification of resistance mutants [9] [10] [11] [12]. Many studies have suggested that the combined treatments might be an effective regimen to restrict the emergence of drug-resistance mutants [13] [14].…”