Levofloxacin Efflux and smeD in Clinical Isolates of Stenotrophomonas maltophilia.
Trimethoprim-sulfamethoxazole is the first-line antimicrobial combination for Stenotrophomonas maltophilia infections. However, allergy or intolerance and increasing resistance limit the use of trimethoprim-sulfamethoxazole. Quinolones can be used as an alternative therapeutic option, but resistance can emerge rapidly during therapy. We analyzed the contribution of SmeABC and SmeDEF efflux pumps to levofloxacin resistance in clinical isolates of S. maltophilia. Nonduplicate clinical isolates of S. maltophilia were collected in 2010 from 11 university hospitals (n = 102). Fifty-five levofloxacin nonsusceptible (minimum inhibitory concentration [MIC] ≥4 μg/ml) and 47 susceptible (MIC ≤2 μg/ml) isolates were tested for efflux pump overexpression. Real-time reverse transcription-PCR was performed for amplification and quantification of smeB, smeC, smeD, and smeF mRNA. To determine which antimicrobials were affected by smeD overexpression, the growth rates of a levofloxacin-susceptible S. maltophilia isolate were compared by measuring absorbance of antimicrobial-supplemented Luria-Bertani broth (LB) cultures with or without triclosan. Significant relationships between sme gene overexpression and resistance were observed for smeD against levofloxacin, smeC and smeF against ceftazidime, and smeC against ticarcillin-clavulanate. The mean MICs of moxifloxacin and tigecycline did not significantly differ for isolates with or without overexpression of smeB, smeC, and smeF, but were significantly higher for isolates with smeD overexpression. The mean MICs of amikacin were significantly higher for smeC or smeF overexpressing isolates. Increased growth of a levofloxacin-susceptible isolate was observed in LB with 1/2 MIC levofloxacin in the presence of triclosan. These data suggest that the expression of smeD plays a role in levofloxacin resistance in S. maltophilia.
1 Department of Internal Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Korea.
So Young
SY
Chong
2 Department of Laboratory Medicine, Yonsei University College of Medicine , Seoul, Korea.|3 Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, Korea.
Kyungwon
K
Lee
3 Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, Korea.|4 Department of Laboratory Medicine, Ewha Womans University School of Medicine , Seoul, Korea.
Hae-Sun
HS
Chung
3 Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, Korea.|5 Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Korea.
Seong Geun
SG
Hong
3 Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, Korea.
Younghee
Y
Suh
2 Department of Laboratory Medicine, Yonsei University College of Medicine , Seoul, Korea.|3 Research Institute of Bacterial Resistance, Yonsei University College of Medicine , Seoul, Korea.
Yunsop
Y
Chong
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002442:Ceftazidime / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests / Q000379:methods; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D000077266:Moxifloxacin; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000378:metabolism*; D013982:Ticarcillin / Q000494:pharmacology; D000078304:Tigecycline; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; C417265:SmeD protein, Stenotrophomonas maltophilia; D064704:Levofloxacin; D000078304:Tigecycline; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D002442:Ceftazidime; D013982:Ticarcillin; D008911:Minocycline; D000077266:Moxifloxacin
SmeDEF pump; Stenotrophomonas maltophilia; biocide; levofloxacin resistance