Chong So Young, Lee Kyungwon, Chung Hae-Sun, Hong Seong Geun, Suh Younghee, Chong Yunsop
1 Department of Internal Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Korea.
2 Department of Laboratory Medicine, Yonsei University College of Medicine , Seoul, Korea.
Microb Drug Resist. 2017 Mar;23(2):163-168. doi: 10.1089/mdr.2015.0228. Epub 2016 Jun 13.
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.
复方新诺明是嗜麦芽窄食单胞菌感染的一线抗菌组合。然而，过敏或不耐受以及耐药性增加限制了复方新诺明的使用。喹诺酮类药物可作为替代治疗选择，但治疗期间耐药性可能迅速出现。我们分析了SmeABC和SmeDEF外排泵对嗜麦芽窄食单胞菌临床分离株左氧氟沙星耐药性的影响。2010年从11所大学医院收集了非重复的嗜麦芽窄食单胞菌临床分离株（n = 102）。对55株左氧氟沙星不敏感（最低抑菌浓度[MIC]≥4μg/ml）和47株敏感（MIC≤2μg/ml）的分离株进行外排泵过表达检测。采用实时逆转录PCR对smeB、smeC、smeD和smeF mRNA进行扩增和定量。为了确定哪些抗菌药物受smeD过表达影响，通过测量添加或不添加三氯生的抗菌补充Luria-Bertani肉汤（LB）培养物的吸光度，比较了一株左氧氟沙星敏感的嗜麦芽窄食单胞菌分离株的生长速率。观察到smeD与左氧氟沙星耐药、smeC和smeF与头孢他啶耐药以及smeC与替卡西林-克拉维酸耐药之间存在sme基因过表达与耐药的显著关系。对于有无smeB、smeC和smeF过表达的分离株，莫西沙星和替加环素的平均MIC无显著差异，但smeD过表达的分离株平均MIC显著更高。smeC或smeF过表达的分离株阿米卡星的平均MIC显著更高。在含1/2 MIC左氧氟沙星的LB中，三氯生存在时观察到一株左氧氟沙星敏感分离株的生长增加。这些数据表明，smeD的表达在嗜麦芽窄食单胞菌对左氧氟沙星的耐药性中起作用。
