In vitro Activity of Pentamidine Alone and in Combination With Aminoglycosides, Tigecycline, Rifampicin, and Doripenem Against Clinical Strains of Carbapenemase-Producing and/or Colistin-Resistant Enterobacteriaceae.
In vitro Activity of Pentamidine Alone and in Combination With Aminoglycosides, Tigecycline, Rifampicin, and Doripenem Against Clinical Strains of Carbapenemase-Producing and/or Colistin-Resistant Enterobacteriaceae.
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DOI：
10.3389/fcimb.2018.00363
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发表时间：
2018
影响因子：
5.7
通讯作者：
Pachón-Ibáñez ME
中科院分区：
文献类型：
--
作者：
Cebrero-Cangueiro T;Álvarez-Marín R;Labrador-Herrera G;Smani Y;Cordero-Matía E;Pachón J;Pachón-Ibáñez ME
肠杆菌科引起不同类型的社区和医院获得性感染。此外，耐多药肠杆菌科细菌的传播是一个公共卫生问题，世界卫生组织将其列为寻找新抗生素至关重要的病原体之一。本研究的目的是分析喷他脒单独使用以及与庆大霉素、妥布霉素、阿米卡星、替加环素、利福平或多利培南联合使用对8株产碳青霉烯酶和/或粘菌素耐药肠杆菌科临床菌株的体外活性：5株产碳青霉烯酶肺炎克雷伯菌、1株产碳青霉烯酶大肠埃希菌和2株粘菌素耐药阴沟肠杆菌。MIC和MBC按照标准方案测定。根据EUCAST折点解释所有抗生素的MIC结果，但利福平使用法国FSM折点。通过时间-杀灭曲线测量喷他脒单独和与浓度为1xMIC的抗生素组合的杀菌和协同活性。对其中一个菌株，K.还在喷他脒的1/2xMIC下进行肺炎克雷伯氏菌OXA-48/CTX-M-15时间-杀灭曲线。所有研究均一式三份进行。喷他脒MIC范围为200-800 μg/mL。庆大霉素、妥布霉素、阿米卡星、替加环素和多利培南的敏感率分别为50%、12.5%、62.5%、87.5%和62.5%。只有两个E。梭菌菌株对利福平敏感。喷他脒单独在1xMIC时对除大肠杆菌外的所有菌株均显示杀菌活性。cloestrogen 32菌株。单独的喷他脒的杀菌活性也在组合中观察到。喷他脒的联合用药对大肠杆菌有协同作用。在24 h用阿米卡星和妥布霉素，在8 h用替加环素。喷他脒加利福平的组合显示出对更多菌株的协同活性（八分之五）。喷他脒加多利培南对任何菌株均未显示协同作用。在1/2xMIC下，喷他脒与所有研究的组合对K.肺炎OXA-48/CTX-M-15菌株。总之，喷他脒单独和组合显示出对产碳青霉烯酶和/或粘菌素耐药肠杆菌科的体外活性。喷他脒似乎是治疗这些病原体引起的感染的一个有希望的选择。
Enterobacteriaceae cause different types of community- and hospital-acquired infections. Moreover, the spread of multidrug-resistant Enterobacteriaceae is a public health problem and the World Health Organization pointed them among the pathogens in which the search of new antibiotics is critical. The objective of this study was to analyze the in vitro activity of pentamidine alone and in combination with gentamicin, tobramycin, amikacin, tigecycline, rifampicin, or doripenem against eight clinical strains of carbapenemase-producing and/or colistin-resistant Enterobacteriaceae: five carbapenemase-producing Klebsiella pneumoniae, one carbapenemase-producing Escherichia coli, and two colistin-resistant Enterobacter cloacae. MIC and MBC were determined following standard protocols. MIC results were interpreted for all the antibiotics according to the EUCAST breakpoints but for rifampicin in which the French FSM breakpoint was used. Bactericidal and synergistic activity of pentamidine alone and in combination with antibiotics at concentrations of 1xMIC was measured by time-kill curves. For one selected strain, K. pneumoniae OXA-48/CTX-M-15 time-kill curves were performed also at 1/2xMIC of pentamidine. All studies were performed in triplicate. Pentamidine MIC range was 200–800 μg/mL. The 50, 12.5, 62.5, 87.5, and 62.5% of the strains were susceptible to gentamicin, tobramycin, amikacin, tigecycline, and doripenem, respectively. Only the two E. cloacae strains were susceptible to rifampicin. Pentamidine alone at 1xMIC showed bactericidal activity against all strains, except for the E. cloacae 32 strain. The bactericidal activity of pentamidine alone was also observed in combination. The combinations of pentamidine were synergistic against E. cloacae 32 with amikacin and tobramycin at 24 h and with tigecycline at 8 h. Pentamidine plus rifampicin was the combination that showed synergistic activity against more strains (five out of eight). Pentamidine plus doripenem did not show synergy against any strain. At 1/2xMIC, pentamidine was synergistic with all the studied combinations against the K. pneumoniae OXA-48/CTX-M-15 strain. In summary, pentamidine alone and in combination shows in vitro activity against carbapenemase-producing and/or colistin-resistant Enterobacteriaceae. Pentamidine appears to be a promising option to treat infections caused by these pathogens.
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DOI：
10.1038/nrd3957-c1
发表时间：
2013-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.2
作者：
Pachón-Ibáñez ME;Labrador-Herrera G;Cebrero-Cangueiro T;Díaz C;Smani Y;Del Palacio JP;Rodríguez-Baño J;Pascual A;Pachón J;Conejo MC
通讯作者：
Conejo MC
影响因子：
2.9
作者：
Nguewa, PA;Fuertes, MA;Pérez, JM
通讯作者：
Pérez, JM
影响因子：
14.2
作者：
Magiorakos, A. -P.;Srinivasan, A.;Monnet, D. L.
通讯作者：
Monnet, D. L.
影响因子：
4.9
作者：
Souli, Maria;Galani, Irene;Giamarellou, Helen
通讯作者：
Giamarellou, Helen