Erdem Fatma, Díez-Aguilar María, Oksuz Lutfiye, Kayacan Cigdem, Abulaila Ayham, Oncul Oral, Morosini María Isabel, Cantón Rafael, Aktas Zerrin
1Department of Medical Microbiology, Adana City Training and Research Hospital, Department of Medical Microbiology, Adana, Turkey.
2Servicio de Microbiología, Hospital Universitario La Princesa, Madrid, Spain.
Acta Microbiol Immunol Hung. 2022 Jun 14;69(3):215-219. doi: 10.1556/030.2022.01785. Print 2022 Sep 16.
Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study.Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-meropenem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as ≥3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as ≥2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, blaKPC and blaCTX-M-1 genes was screened by PCR using specific primers.The blaOXA-48 gene was identified together with blaCTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indifferent effect on the strains.Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism.
治疗由产OXA-48碳青霉烯酶的多重耐药菌株引起的感染通常需要联合治疗。本研究评估了不同抗生素组合对多重耐药（MDR）肺炎克雷伯菌分离株的体外作用。通过时间杀菌试验测试了美罗培南-妥布霉素（MER+TOB）、美罗培南-环丙沙星（MER+CIP）、黏菌素-美罗培南（COL+MER）、黏菌素-环丙沙星（COL+CIP）和黏菌素-妥布霉素（COL+TOB）组合。单独使用每种抗生素以及以其Cmax值组合使用时，在1、2、4、6、8、12和24小时对4株临床肺炎克雷伯菌分离株进行测试。还在30分钟时评估了黏菌素及其联合用药的效果。杀菌活性定义为与初始接种物相比CFU mL-1降低≥3log10。协同作用定义为与最有效的单一药物相比，联合用药使CFU mL-1降低≥2log10。使用特异性引物通过PCR筛选blaOXA-48、blaNDM、blaVIM、blaIMP、blaKPC和blaCTX-M-1基因的存在情况。在所有分离株中均鉴定出blaOXA-48基因与blaCTXM-1组基因。COL+MER显示出协同和杀菌作用。MER+TOB对两株菌株显示出协同和杀菌作用，不过在另外两株菌株上24小时时出现了再生长。MER+CIP对这些菌株表现出无作用。联合治疗可能是治疗MDR肺炎克雷伯菌感染的一种潜在替代方法。这种联合用药可能会防止耐药性的产生以及黏菌素单药治疗的副作用。MER+TOB和MER+CIP可能具有菌株依赖性作用，不一定总能产生协同作用。
