Nathália Abichabki, Gilberto Gambero Gaspar, Luísa Vieira Zacharias, Renata Helena Cândido Pocente, Denissani Aparecida Ferrari Santos Lima, Natália Augusta Barbosa de Freitas, Guilherme Thomaz Pereira Brancini, Natália Columbaro Moreira, Gilberto Úbida Leite Braga, Fernando Bellissimo-Rodrigues, Valdes Roberto Bollela, Ana Lúcia Costa Darini, Leonardo Neves Andrade
{"title":"利福平联合多粘菌素 B 的最小有效抗生素浓度 (MEAC) 对广泛耐药、耐碳青霉烯类和耐多粘菌素 B 的肺炎克雷伯菌临床分离株的体外协同作用。","authors":"Nathália Abichabki, Gilberto Gambero Gaspar, Luísa Vieira Zacharias, Renata Helena Cândido Pocente, Denissani Aparecida Ferrari Santos Lima, Natália Augusta Barbosa de Freitas, Guilherme Thomaz Pereira Brancini, Natália Columbaro Moreira, Gilberto Úbida Leite Braga, Fernando Bellissimo-Rodrigues, Valdes Roberto Bollela, Ana Lúcia Costa Darini, Leonardo Neves Andrade","doi":"10.1007/s00284-024-03897-1","DOIUrl":null,"url":null,"abstract":"<p><p>We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In Vitro Synergistic Activity of Rifampicin Combined with Minimal Effective Antibiotic Concentration (MEAC) of Polymyxin B Against Extensively Drug-Resistant, Carbapenem-, and Polymyxin B-Resistant Klebsiella pneumoniae Clinical Isolates.\",\"authors\":\"Nathália Abichabki, Gilberto Gambero Gaspar, Luísa Vieira Zacharias, Renata Helena Cândido Pocente, Denissani Aparecida Ferrari Santos Lima, Natália Augusta Barbosa de Freitas, Guilherme Thomaz Pereira Brancini, Natália Columbaro Moreira, Gilberto Úbida Leite Braga, Fernando Bellissimo-Rodrigues, Valdes Roberto Bollela, Ana Lúcia Costa Darini, Leonardo Neves Andrade\",\"doi\":\"10.1007/s00284-024-03897-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s00284-024-03897-1\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00284-024-03897-1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
In Vitro Synergistic Activity of Rifampicin Combined with Minimal Effective Antibiotic Concentration (MEAC) of Polymyxin B Against Extensively Drug-Resistant, Carbapenem-, and Polymyxin B-Resistant Klebsiella pneumoniae Clinical Isolates.
We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.