{"title":"针对耐多药和耐碳青霉烯类革兰氏阴性菌的新开发抗生素:作用和耐药机制","authors":"Sena Nur Başaran, Lütfiye Öksüz","doi":"10.1007/s00203-025-04298-z","DOIUrl":null,"url":null,"abstract":"<div><p>Antimicrobial resistance stands as one of the most urgent global health concerns in the twenty-first century, with projections suggesting that deaths related to drug-resistant infections could escalate to 10 million by 2050 if proactive measures are not implemented. In intensive care settings, managing infections caused by multidrug-resistant (MDR) Gram-negative bacteria is particularly challenging, posing a significant threat to public health and contributing substantially to both morbidity and mortality. There are numerous studies on the antibiotics responsible for resistance in Gram-negative bacteria, but comprehensive research on resistance mechanisms against new antibiotics is rare. Considering the possibility that antibiotics may no longer be effective in combating diseases, it is crucial to comprehend the problem of emerging resistance to newly developed antibiotics and to implement preventive measures to curb the spread of resistance. Mutations in porins and efflux pumps play a crucial role in antibiotic resistance by altering drug permeability and active efflux. Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.</p><p>This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"207 5","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms\",\"authors\":\"Sena Nur Başaran, Lütfiye Öksüz\",\"doi\":\"10.1007/s00203-025-04298-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Antimicrobial resistance stands as one of the most urgent global health concerns in the twenty-first century, with projections suggesting that deaths related to drug-resistant infections could escalate to 10 million by 2050 if proactive measures are not implemented. In intensive care settings, managing infections caused by multidrug-resistant (MDR) Gram-negative bacteria is particularly challenging, posing a significant threat to public health and contributing substantially to both morbidity and mortality. There are numerous studies on the antibiotics responsible for resistance in Gram-negative bacteria, but comprehensive research on resistance mechanisms against new antibiotics is rare. Considering the possibility that antibiotics may no longer be effective in combating diseases, it is crucial to comprehend the problem of emerging resistance to newly developed antibiotics and to implement preventive measures to curb the spread of resistance. Mutations in porins and efflux pumps play a crucial role in antibiotic resistance by altering drug permeability and active efflux. Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.</p><p>This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.</p></div>\",\"PeriodicalId\":8279,\"journal\":{\"name\":\"Archives of Microbiology\",\"volume\":\"207 5\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-04-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00203-025-04298-z\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00203-025-04298-z","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms
Antimicrobial resistance stands as one of the most urgent global health concerns in the twenty-first century, with projections suggesting that deaths related to drug-resistant infections could escalate to 10 million by 2050 if proactive measures are not implemented. In intensive care settings, managing infections caused by multidrug-resistant (MDR) Gram-negative bacteria is particularly challenging, posing a significant threat to public health and contributing substantially to both morbidity and mortality. There are numerous studies on the antibiotics responsible for resistance in Gram-negative bacteria, but comprehensive research on resistance mechanisms against new antibiotics is rare. Considering the possibility that antibiotics may no longer be effective in combating diseases, it is crucial to comprehend the problem of emerging resistance to newly developed antibiotics and to implement preventive measures to curb the spread of resistance. Mutations in porins and efflux pumps play a crucial role in antibiotic resistance by altering drug permeability and active efflux. Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.
This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.
期刊介绍:
Research papers must make a significant and original contribution to
microbiology and be of interest to a broad readership. The results of any
experimental approach that meets these objectives are welcome, particularly
biochemical, molecular genetic, physiological, and/or physical investigations into
microbial cells and their interactions with their environments, including their eukaryotic hosts.
Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published.
Theoretical papers and those that report on the analysis or ''mining'' of data are
acceptable in principle if new information, interpretations, or hypotheses
emerge.