Fernández-Cuenca Felipe, Tomás María, Caballero-Moyano Francisco-Javier, Bou Germán, Martínez-Martínez Luis, Vila Jordi, Pachón Jerónimo, Cisneros José-Miguel, Rodríguez-Baño Jesús, Pascual Álvaro
Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain
Servicio de Microbiología, Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain.
J Antimicrob Chemother. 2015 Dec;70(12):3222-9. doi: 10.1093/jac/dkv262. Epub 2015 Sep 10.
The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.
Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.
Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan(®) was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan(®) was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan(®).
Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan(®) may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).
本研究的目的是分析鲍曼不动杆菌对杀菌剂敏感性降低与以下因素之间是否存在关联：（i）抗菌药物耐药性（共同耐药性）、（ii）流行（优势）克隆、（iii）适应性变化或（iv）与外排泵和孔蛋白相关基因的表达。
对49株非克隆相关的鲍曼不动杆菌分离株测定其对杀菌剂和抗菌药物的敏感性。通过分光光度法测定以平均世代时间表示的生物学代价。采用定量实时逆转录聚合酶链反应（qRT-PCR）测定编码几种外排泵和孔蛋白的基因的相对表达。
对葡萄糖酸洗必泰、苯扎氯铵和氯己定（Irgasan®）的敏感性降低与对氨基糖苷类、四环素和环丙沙星的耐药性相关（P<0.05）。暴露于这些杀菌剂的分离株Ab70（流行克隆）对碳青霉烯类、氨基糖苷类、多西环素和环丙沙星的最低抑菌浓度（MIC）增加了≥2倍稀释度。在流行克隆中，对奥山（Orsan®）敏感性降低的情况比非流行克隆更常见（P<0.05）。暴露于苯扎氯铵前后，Ab70的平均世代时间分别为57.8分钟和78.1分钟（P=0.02）。暴露于葡萄糖酸洗必泰后，Ab46和Ab70中abeS和adeB的相对表达增加，但暴露于氯己定（Irgasan®）后，ompA和carO的相对表达降低。
对杀菌剂敏感性降低与对碳青霉烯类、氨基糖苷类、四环素和环丙沙星的共同耐药性相关。对奥山（Orsan®）敏感性降低可能是流行克隆的一个标志。获得对苯扎氯铵敏感性降低具有生物学代价。暴露于杀菌剂会影响与某些外排泵基因（表达增加）或孔蛋白（表达降低）相关基因的相对表达。
