An Investigation Of Fluoroquinolone Molecular Resistant Mechanism Of Stenotrophomonas Maltophilia

Objective: To survey the antibiotics resistances of Stenotrophomonas maltophilia and guide the rational antibiotics usage in Stenotrophomonas maltophilia infection therapy. To investigate the presence of an active efflux mechanism by the MICs of fluoroquinolones in combination with 0.5mg/L CCCP. To research topoisomerase II and IV quinolone reistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different resistant levels of quinolone susceptibility.Methods: Minimal inhibitory concentrations(MICs) of 9 antibiotics against Stenotrophomonas maltophilia were measured using two-fold agar dilution method. The MICs of four fluoroquinolones were also determined in combination with 0.5mg of CCCP per liter. An efflux mechanism was inferred to be present when the quinolone MIC in the presence of CCCP was at least fourfold less than the corresponding MIC in the absence of CCCP. Five strains which MIC of ciprofloxacin is more than 2mg/L and is negative of efflux mechanism, were amplified their QRDRs of gyrA and pare, purified the fragment and analyzed nucleotide sequences.Results: A total of 144 strains of Stenotrophomonas maltophilia are multi-drug resistant. But the resistant ratio of trimethoprim-sulfamethoxazole, ticarcillin-clavavulanic acid and fluoroquinolones are lower, especially new fluoroquinolones have stronger antimicrobial activities. CCCP may enhance the fluoroquinolones activity in vitro, especially for ciprofloxacin. Active efflux mechanism exist not only in FQNS resistant strains, but also in FQNS susceptible strains. But it affects bigger in FQNS resistant strains. In Stenotrophomonas maltophilia DNA gyrase, the absence of changes at positions 83 and 87 , commonly involved in quinolones resistance in gram-negative bacteria, and there is Gin but not Ser or Thr. Of five strains, one strain show a ParE amino acid change in positions 402, the other is in positions 432, but the mutations are not associated with resistant of FQNS.Conelusions: Clinical isolating rate of Stenotrophomonas maltophilia strains has been rising. In Stenotrophomonas maltophilia infection therapy, the empiric treatment is trimethoprim-sulfamethoxazole and fluoroquinolones. For serious infection antibiotic therapy may choose trimethoprim-sulfamethoxazole combine with ticarcillin-clavavulanic acid or new fluoroquinolones. In vitro, CCCPCCCP may enhance the fluoroquinolones activity, especially for FQNS resistant strains is bigger. FQNS resistance of Stenotrophomonas maltophilia is related to active efflux pump, and may be correlated with a low level of permeability. But it is not clear whether resistance is related to the mutants in DNA gyrase and topoisomerase IV.