Previous studies have found that ciprofloxacin showed a higher number of resistant strains than levofloxacin among the clinical isolates of Enterobacteriaceae[5–7, 9–11, 17]. In the present investigation, we also observed similar data among the clinical isolates of K. pneumoniae and E. coli. Moreover, we found that resistance difference to ciprofloxacin and levofloxacin was of statistical significance among the isolates with QRDR mutations. Such differences might be mainly addressed in terms of the different CLSI resistant breakpoints (4 μg/ml for ciprofloxacin and 8 μg/ml for levofloxacin), which are supposed to integrate more strains with an elevated MIC for ciprofloxacin into the resistant bacterial population.
Nevertheless, a cluster of studies have shown that gyrase had different sensitivity and affinity to ciprofloxacin and levofloxacin, owing to the molecular structural difference of the two fluoroquinolones [1, 21–23]. One can postulate that different amino acid substitution in QRDR might play different roles in resistance to the two agents. In the present work, we investigated the relationship between the drug-resistance between ciprofloxacin and levofloxacin and specific mutations of gyrA gene. In combination with relevant studies reported in PubMed, we analyzed the relationship between QRDR mutations and the resistance to ciprofloxacin and levofloxacin. Of the 14 patterns of QRDR mutations found in 327 Enterobacteriaceae isolates, 5 patterns of mutations were related to ciprofloxacin and levofloxacin resistance. Two single mutations (Ser83Phe and Ser83Leu) were related to ciprofloxacin resistance but not to levofloxacin resistance. None of the remaining 7 patterns of mutation were found to be related to resistance to any one of the two FQs. Further study about the interactions between various amino acid substitutions and different FQs molecules would give a comparison of amino acid preference for FQ, and that a certain amino acid substitution may bring about a varied resistance to different FQs.
In our study, among 5 QRDR mutations in the gyrA gene related to both ciprofloxacin and levofloxacin resistance, isolates with Ser83Leu+Asp87Asn mutation were shown to have statistically different drug resistance between ciprofloxacin and levofloxacin. It could be inferred that such resistance difference between the two drugs was mainly due to Ser83Leu+Asp87Asn mutation. As for the other types of effective mutations, no statistically significant difference was found in drug resistance difference between the two FQs among the isolates with these mutations.
Additionally, there were four resistant isolates without gyrA mutations in this study. None of them were found to harbor plasmid-mediated quinolone resistance genes. Further examination about the active efflux or permeability changes for the four strains is needed.
Taken together, we found that there is a statistical difference in antimicrobial resistance between ciprofloxacin and levofloxacin among clinical isolates of Enterobacteriaceae. Based upon the effectiveness of resistance, mutation patterns of QRDR can be divided into effective mutation and neutral mutation. Ser83Leu+Asp87Asn mutation, as an effective mutation, caused the drug resistance difference between ciprofloxacin and levofloxacin in Enterobacteriaceae isolates.