{"title":"zidebactam/cefepime (WCK 5222)是一种β-内酰胺增强剂/β-内酰胺复方制剂，对耐碳青霉烯类和耐秋水仙碱肺炎克雷伯菌分离物的体外活性。","authors":"Yamuna Devi Bakthavatchalam , Chaitra Shankar , Christo Jeyaraj , Ayyanraj Neeravi , Purva Mathur , Vasant Nagvekar , Sangeetha Nithiyanandam , Kamini Walia , Balaji Veeraraghavan","doi":"10.1016/j.diagmicrobio.2024.116561","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>In vitro activity of β-lactam enhancer/β-lactam combination zidebactam/cefepime was evaluated against carbapenem- and colistin-resistant <em>Klebsiella pneumoniae</em> isolates.</div></div><div><h3>Methods</h3><div>Non duplicate <em>K. pneumoniae</em> (<em>n</em>=185), resistant to colistin as well as non-susceptible to carbapenems were collected (2018-2019) at two large tertiary care hospitals in India. Colistin resistance-conferring genes <em>mcr1</em> and <em>mcr3</em> were screened among 123 of 185 randomly-selected isolates. These isolates were also subjected to multi-locus sequence typing (MLST). Additionally, alterations in <em>mgrB</em> were screened in 109 of these 123 isolates. All the study isolates were screened for presence of carbapenemases genes. MICs of zidebactam/cefepime, colistin, carbapenems, ceftazidime/avibactam, imipenem/relebactam, amikacin and piperacillin/tazobactam were determined by reference CLSI broth dilution method.</div></div><div><h3>Results</h3><div>Among the isolates, 65.4% (121/185) carried <em>bla</em><sub>OXA-48-like</sub> gene and 27.6% isolates (51/185) carried dual carbapenemase genes; <em>bla</em><sub>OXA-48-like</sub> and <em>bla</em><sub>NDM</sub>. Of the remainder, 8 isolates carried <em>bla</em><sub>NDM</sub> and 5 isolates lacked carbapenemases gene despite being carbapenem-resistant. None of the isolates showed presence of <em>mcr1</em> and <em>mcr3</em>. Out of 109 isolates analysed for <em>mgrB</em>, 36 showed mutational changes. The MLST profile revealed at least 14 unique sequence types with ST231 being the dominant clone. All the isolates showed colistin MICs >2 mg/L and were non-susceptible to carbapenems. Zidebactam/cefepime demonstrated potent activity with MIC<sub>50</sub> and MIC<sub>90</sub> of 1 and 2 mg/L, respectively. MIC<sub>90</sub>s of amikacin, ceftazidime/avibactam and imipenem/relebactam were >32 mg/L.</div></div><div><h3>Conclusion</h3><div>Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant <em>K. pneumoniae</em> isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism.</div></div>","PeriodicalId":11329,"journal":{"name":"Diagnostic microbiology and infectious disease","volume":"111 1","pages":"Article 116561"},"PeriodicalIF":2.1000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vitro activity of zidebactam/cefepime (WCK 5222), a β-lactam enhancer/ β-lactam combination against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates\",\"authors\":\"Yamuna Devi Bakthavatchalam , Chaitra Shankar , Christo Jeyaraj , Ayyanraj Neeravi , Purva Mathur , Vasant Nagvekar , Sangeetha Nithiyanandam , Kamini Walia , Balaji Veeraraghavan\",\"doi\":\"10.1016/j.diagmicrobio.2024.116561\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><div>In vitro activity of β-lactam enhancer/β-lactam combination zidebactam/cefepime was evaluated against carbapenem- and colistin-resistant <em>Klebsiella pneumoniae</em> isolates.</div></div><div><h3>Methods</h3><div>Non duplicate <em>K. pneumoniae</em> (<em>n</em>=185), resistant to colistin as well as non-susceptible to carbapenems were collected (2018-2019) at two large tertiary care hospitals in India. Colistin resistance-conferring genes <em>mcr1</em> and <em>mcr3</em> were screened among 123 of 185 randomly-selected isolates. These isolates were also subjected to multi-locus sequence typing (MLST). Additionally, alterations in <em>mgrB</em> were screened in 109 of these 123 isolates. All the study isolates were screened for presence of carbapenemases genes. MICs of zidebactam/cefepime, colistin, carbapenems, ceftazidime/avibactam, imipenem/relebactam, amikacin and piperacillin/tazobactam were determined by reference CLSI broth dilution method.</div></div><div><h3>Results</h3><div>Among the isolates, 65.4% (121/185) carried <em>bla</em><sub>OXA-48-like</sub> gene and 27.6% isolates (51/185) carried dual carbapenemase genes; <em>bla</em><sub>OXA-48-like</sub> and <em>bla</em><sub>NDM</sub>. Of the remainder, 8 isolates carried <em>bla</em><sub>NDM</sub> and 5 isolates lacked carbapenemases gene despite being carbapenem-resistant. None of the isolates showed presence of <em>mcr1</em> and <em>mcr3</em>. Out of 109 isolates analysed for <em>mgrB</em>, 36 showed mutational changes. The MLST profile revealed at least 14 unique sequence types with ST231 being the dominant clone. All the isolates showed colistin MICs >2 mg/L and were non-susceptible to carbapenems. Zidebactam/cefepime demonstrated potent activity with MIC<sub>50</sub> and MIC<sub>90</sub> of 1 and 2 mg/L, respectively. MIC<sub>90</sub>s of amikacin, ceftazidime/avibactam and imipenem/relebactam were >32 mg/L.</div></div><div><h3>Conclusion</h3><div>Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant <em>K. pneumoniae</em> isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism.</div></div>\",\"PeriodicalId\":11329,\"journal\":{\"name\":\"Diagnostic microbiology and infectious disease\",\"volume\":\"111 1\",\"pages\":\"Article 116561\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diagnostic microbiology and infectious disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0732889324003869\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diagnostic microbiology and infectious disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0732889324003869","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
In vitro activity of zidebactam/cefepime (WCK 5222), a β-lactam enhancer/ β-lactam combination against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates
Objectives
In vitro activity of β-lactam enhancer/β-lactam combination zidebactam/cefepime was evaluated against carbapenem- and colistin-resistant Klebsiella pneumoniae isolates.
Methods
Non duplicate K. pneumoniae (n=185), resistant to colistin as well as non-susceptible to carbapenems were collected (2018-2019) at two large tertiary care hospitals in India. Colistin resistance-conferring genes mcr1 and mcr3 were screened among 123 of 185 randomly-selected isolates. These isolates were also subjected to multi-locus sequence typing (MLST). Additionally, alterations in mgrB were screened in 109 of these 123 isolates. All the study isolates were screened for presence of carbapenemases genes. MICs of zidebactam/cefepime, colistin, carbapenems, ceftazidime/avibactam, imipenem/relebactam, amikacin and piperacillin/tazobactam were determined by reference CLSI broth dilution method.
Results
Among the isolates, 65.4% (121/185) carried blaOXA-48-like gene and 27.6% isolates (51/185) carried dual carbapenemase genes; blaOXA-48-like and blaNDM. Of the remainder, 8 isolates carried blaNDM and 5 isolates lacked carbapenemases gene despite being carbapenem-resistant. None of the isolates showed presence of mcr1 and mcr3. Out of 109 isolates analysed for mgrB, 36 showed mutational changes. The MLST profile revealed at least 14 unique sequence types with ST231 being the dominant clone. All the isolates showed colistin MICs >2 mg/L and were non-susceptible to carbapenems. Zidebactam/cefepime demonstrated potent activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. MIC90s of amikacin, ceftazidime/avibactam and imipenem/relebactam were >32 mg/L.
Conclusion
Zidebactam/cefepime combination was highly active against multi-clonal, carbapenem-non-susceptible and colistin-resistant K. pneumoniae isolates producing OXA-48-like (Ambler class D) or/and NDM (Ambler class B) carbapenemases, thus potentially offering a valuable treatment options for infections caused by such pan-drug resistant resistotypes. Though, zidebactam is not an inhibitor of class B and D β-lactamases, potent activity of zidebactam/cefepime combination is attributable to β-lactam enhancer mechanism.
期刊介绍：
Diagnostic Microbiology and Infectious Disease keeps you informed of the latest developments in clinical microbiology and the diagnosis and treatment of infectious diseases. Packed with rigorously peer-reviewed articles and studies in bacteriology, immunology, immunoserology, infectious diseases, mycology, parasitology, and virology, the journal examines new procedures, unusual cases, controversial issues, and important new literature. Diagnostic Microbiology and Infectious Disease distinguished independent editorial board, consisting of experts from many medical specialties, ensures you extensive and authoritative coverage.
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