JAC-Antimicrobial Resistance最新文献

{"title":"Phenotypic and genomic analysis of bacteria from war wounds in Dnipro, Ukraine.","authors":"Dmytro Stepanskyi, Oksana Ishchenko, Ting Luo, Francois Lebreton, Jason W Bennett, Iryna Kovalenko, Patrick McGann","doi":"10.1093/jacamr/dlae090","DOIUrl":"10.1093/jacamr/dlae090","url":null,"abstract":"<p><strong>Objectives: </strong>To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine.</p><p><strong>Methods: </strong>Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro.</p><p><strong>Results: </strong>The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases.</p><p><strong>Conclusions: </strong>Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of screening algorithms to detect rectal colonization with carbapenemase-producing Enterobacterales in a resource-limited setting.","authors":"Thi Anh Mai Pham, Tung Xuan Nguyen, Troung Nhat My, Lan Thi Le, Huyen Thi Vu, Ngoc Thi Bich Hoang, Dien M Tran, Linh Viet Nguyen, Phuc D Pham, Dennis Nurjadi, Flavie Goutard, Thirumalaisamy P Velavan, Van Anh Thi Dinh, Y M Gildas Hounmanou, Bent Jörgensen, Le Huu Song, Nhung T T Nguyen, Etienne Loire, Åse Östholm, Lennart E Nilsson, Tuyet Hanh T Tran, Phuc H Phan, Anders Dalsgaard, Mattias Larsson, Linus Olson, Håkan Hanberger","doi":"10.1093/jacamr/dlae089","DOIUrl":"10.1093/jacamr/dlae089","url":null,"abstract":"<p><strong>Objectives: </strong>To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources.</p><p><strong>Methods: </strong>A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i> and <i>Enterobacter cloacae</i> complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases.</p><p><strong>Conclusions: </strong>These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic prescribing and bacterial infection in COVID-19 inpatients in Southeast Asia: a systematic review and meta-analysis.","authors":"Achiraya Chanapal, Hung-Yung Cheng, Helen Lambert, Wenjuan Cong","doi":"10.1093/jacamr/dlae093","DOIUrl":"10.1093/jacamr/dlae093","url":null,"abstract":"<p><strong>Background: </strong>The prescribing of antibiotics to treat COVID-19 patients has been observed to occur frequently, often without clear justification. This trend raises concerns that it may have exacerbated antimicrobial resistance (AMR). Despite longstanding concerns over AMR in Southeast Asian countries, data on this issue are notably lacking.</p><p><strong>Objectives: </strong>To explore the impact of COVID-19 on antibiotic prescribing, bacterial infection prevalence and common resistant pathogens in COVID-19 inpatients.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, Web of Science and ThaiJO (a Thai academic database) to identify studies conducted in ASEAN member countries and published between December 2019 and March 2023. Screening and data extraction were done by two independent reviewers, with results synthesized using random-effects meta-analyses and descriptive statistical analyses. This review was registered with PROSPERO (CRD42023454337).</p><p><strong>Results: </strong>Of the 29 studies (19 750 confirmed COVID-19 cases) included for final analysis, the antibiotic prescribing rate was 62.0% (95%CI: 46.0%-76.0%) with a prescribing rate of 58.0% (21.0%-91.0%) in mild/moderate cases versus 91.0% (82.0%-98.0%) in severe/critical cases. Notably, 80.5% of antibiotics prescribed fall under the WHO AWaRe 'Watch' list, followed by 'Access' at 18.4% and 'Reserve' at 1.0%. The reported bacterial infection prevalence was 16.0% (7.0%-29.0%), with <i>Acinetobacter baumannii</i> being the most common resistant bacterium at 7.7%. Singapore was notable for its lower antibiotic prescribing rate of 17.0% and a lower bacterial infection rate of 10.0%.</p><p><strong>Conclusions: </strong>High antibiotic prescribing rates, disproportionate to bacterial infections and varying practices for COVID-19 inpatients across countries highlight the urgent need for this region to collaborate to tackle and mitigate AMR.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Comparison of carbapenem MIC for NDM-producing Enterobacterales by different AST methods: considerations for media composition.","authors":"Tomefa E Asempa, David P Nicolau","doi":"10.1093/jacamr/dlae091","DOIUrl":"10.1093/jacamr/dlae091","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-prescription sale and dispensing of antibiotics for prophylaxis in broiler chickens in Lusaka District, Zambia: findings and implications on one health.","authors":"Steward Mudenda, Karen Mubanga Mulenga, Ruth Nyirongo, Billy Chabalenge, Chikwanda Chileshe, Victor Daka, Ethel M'kandawire, Elimas Jere, John Bwalya Muma","doi":"10.1093/jacamr/dlae094","DOIUrl":"10.1093/jacamr/dlae094","url":null,"abstract":"<p><strong>Background: </strong>The irrational use of antibiotics in humans and livestock has contributed to the emergence of antimicrobial resistance (AMR). This study investigated the commonly sold and dispensed antibiotics for prophylaxis in broiler chickens in pharmacy and agro-veterinary shop personnel in the Lusaka District of Zambia.</p><p><strong>Methods: </strong>This cross-sectional study was conducted from August 2023 to October 2023 among 200 veterinary medicine dispensers in the Lusaka District of Zambia using a simulated farmer or mystery shopper approach. Data analysis was performed using IBM Statistical Package for Social Sciences version 23.0.</p><p><strong>Results: </strong>Out of the 200 medicine outlets investigated, 23 (11.5%) were agro-veterinary shops, while 177 (88.5%) were community pharmacies. A total of 165 community pharmacies and agro-veterinary shops provided veterinary services in the Lusaka District and sold medicines without prescription giving a 100% non-prescription sale. Of the 178 medicines dispensed for prophylaxis, 88.5% were antibiotics, while 13.5% were vitamins. The most dispensed antibiotic drug for prophylaxis in broiler chickens was oxytetracycline (30.34%), amoxicillin (17.98%) and gentamicin/doxycycline (10.67%).</p><p><strong>Conclusions: </strong>This study revealed a high sale and dispensing of antibiotics for prophylaxis in broiler chickens of which oxytetracycline, amoxicillin and gentamicin/doxycycline were commonly dispensed. There is a need for increased regulatory enforcement of selling antibiotics without a prescription as this may predispose poultry to the development of AMR and possible transmission of superbugs to humans and the environment. Educational interventions should be provided to community pharmacy and agro-veterinary personnel on adhering to antimicrobial stewardship practices when dispensing poultry antibiotics.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of gaming for information, education and communication of AMR: full review of online education resources.","authors":"Romita Trehan, Raphael Goujet, Tina Sharma, Abhinav Vats, Nidhiben Patel, Anshu Bhardwaj","doi":"10.1093/jacamr/dlae080","DOIUrl":"10.1093/jacamr/dlae080","url":null,"abstract":"<p><strong>Background: </strong>The first objective of the Global Action Plan on antimicrobial resistance (AMR) is to improve awareness and understanding of AMR through effective communication, education and training. Towards this several efforts have been made to create AMR awareness resources. The aim of these resources is to inform the public about responsible antibiotic use and drive positive behavioural change. Digital media and specifically games can serve as unique innovative platforms in public communication programmes.</p><p><strong>Objectives: </strong>This study focuses on compiling and evaluating game-based AMR resources. Recognizing the engaging and creative potential of games as learning tools, the primary objective of this study was to identify games that can be used, individually or in combination depending on their unique focus and gameplay experience, for AMR awareness. Furthermore, games are evaluated on five objective criteria and recommendations are made towards further development of gaming resources towards AMR awareness.</p><p><strong>Methods: </strong>Meticulous curation was performed to mine information, education and communication resources, with a primary focus on games for AMR awareness and evaluating them based on game design and gameplay, AMR content and learning, engagement and replay appeal, learning outcomes, and level of difficulty and challenges.</p><p><strong>Results: </strong>In this study, we selected 12 AMR games. Our evaluations, spanning various gamification elements and interactive parameters, informed recommendations for future AMR resource development, including multilevel game design, varied graphics, simple-to-understand rules, sustained challenge and a sense of reward, among others.</p><p><strong>Conclusions: </strong>This study generated the first-ever comprehensive catalogue of AMR games that may assist public communication programmes for AMR awareness. Evaluation of these games led to actionable design recommendations for future resources towards effective communication of AMR complexity, enhanced learning and awareness.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature dependence of the mutation rate towards antibiotic resistance.","authors":"Timo J B Van Eldijk, Eleanor A Sheridan, Guillaume Martin, Franz J Weissing, Oscar P Kuipers, G Sander Van Doorn","doi":"10.1093/jacamr/dlae085","DOIUrl":"10.1093/jacamr/dlae085","url":null,"abstract":"<p><strong>Objectives: </strong>Environmental conditions can influence mutation rates in bacteria. Fever is a common response to infection that alters the growth conditions of infecting bacteria. Here we examine how a temperature change, such as is associated with fever, affects the mutation rate towards antibiotic resistance.</p><p><strong>Methods: </strong>We used a fluctuation test to assess the mutation rate towards antibiotic resistance in <i>Escherichia coli</i> at two different temperatures: 37°C (normal temperature) and 40°C (fever temperature). We performed this measurement for three different antibiotics with different modes of action: ciprofloxacin, rifampicin and ampicillin.</p><p><strong>Results: </strong>In all cases, the mutation rate towards antibiotic resistance turned out to be temperature dependent, but in different ways. Fever temperatures led to a reduced mutation rate towards ampicillin resistance and an elevated mutation rate towards ciprofloxacin and rifampicin resistance.</p><p><strong>Conclusions: </strong>This study shows that the mutation rate towards antibiotic resistance is impacted by a small change in temperature, such as associated with fever. This opens a new avenue to mitigate the emergence of antibiotic resistance by coordinating the choice of an antibiotic with the decision of whether or not to suppress fever when treating a patient. Hence, optimized combinations of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11154133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations on <i>Enterobacter cloacae</i> complex and <i>Klebsiella aerogenes</i> in Spain (SMART 2016-2022).","authors":"Ángel Rodríguez-Villodres, Esperanza Lepe-Balsalobre, José Manuel Ortiz De La Rosa, Salvador Giner Almaraz, Elisa González De Herrero, Emilia Cercenado, Sergio García-Fernández, Rafael Benito, Ricardo Ponz Mir, Rafael Cantón, José Antonio Lepe","doi":"10.1093/jacamr/dlae087","DOIUrl":"10.1093/jacamr/dlae087","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the susceptibility profile to cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations in <i>Enterobacter cloacae</i> complex and <i>Klebsiella aerogenes</i> isolated from intra-abdominal, urinary, respiratory and bloodstream infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain.</p><p><strong>Methods: </strong>The susceptibilities of 759 isolates (473 <i>E. cloacae</i> complex and 286 <i>K. aerogenes</i>) collected in 11 Spanish hospitals from 2016 to 2022 were analysed following the EUCAST 2023 criteria. Molecular characterization looking for β-lactamase genes was performed through PCR and DNA sequencing analysis.</p><p><strong>Results: </strong><i>E. cloacae</i> complex showed resistance to third-generation cephalosporins in 25% of the cases, whereas <i>K. aerogenes</i> was resistant in 35%. Regarding cefepime, resistance in <i>E. cloacae</i> was higher (10%) than in <i>K. aerogenes</i> (2%). Carbapenems showed >85% activity in both microorganisms. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam had good activity against these microorganisms (>95%). In contrast, the activity of ceftolozane/tazobactam was lower (80%). A high proportion of the isolates resistant to new β-lactam/β-lactamase inhibitor combinations carried a carbapenemase, mainly OXA-48-like and VIM-1.</p><p><strong>Conclusions: </strong>Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam show high activity against both <i>E. cloacae</i> complex and <i>K. aerogenes</i> isolates recovered in the SMART-Spain study. In contrast, differences have been found in the case of cefepime, showing more activity against <i>K. aerogenes</i> than <i>E. cloacae</i> complex. These results are useful for antimicrobial stewardship programmes and for the implementation of local and national guidelines.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11154015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the antimicrobial efficacy of ceftriaxone regimens: 1 g twice daily versus 2 g once daily in a murine model of <i>Streptococcus pneumoniae</i> pneumonia.","authors":"Hideo Kato, Mao Hagihara, Shun-Ichi Hiramatsu, Hiroyuki Suematsu, Naoya Nishiyama, Nobuhiro Asai, Hiroshige Mikamo, Kazuko Yamamoto, Takuya Iwamoto","doi":"10.1093/jacamr/dlae092","DOIUrl":"10.1093/jacamr/dlae092","url":null,"abstract":"<p><strong>Background: </strong>Ceftriaxone is administered in regimens of either 2 g once-daily or 1 g twice-daily for the treatment of pneumonia caused by <i>Streptococcus pneumoniae</i>. Previous clinical study suggests the 2 g once-daily regimen is more effective, but comparison of antimicrobial efficacy between are lacking.</p><p><strong>Objectives: </strong>To assess the antimicrobial efficacy of these two ceftriaxone regimens against <i>S. pneumoniae</i> using a murine model of pneumonia.</p><p><strong>Methods: </strong>The study employed three <i>S. pneumoniae</i> isolates with ceftriaxone MICs of 1, 2 and 4 mg/L and two human-simulated regimens based on the blood concentration of ceftriaxone (1 g twice-daily and 2 g once-daily). Antimicrobial activity was quantified based on the change in bacterial counts (Δlog₁₀ cfu/lungs) observed in treated mice after 24 h, relative to the control mice at 0 h.</p><p><strong>Results: </strong>The human-simulated 2 g once-daily regimen of ceftriaxone exhibited significantly higher antimicrobial activity against <i>S. pneumoniae</i> isolates with MICs of 1 and 2 mg/L compared with the 1 g twice-daily regimen (1 mg/L, -5.14 ± 0.19 Δlog₁₀ cfu/lungs versus -3.47 ± 0.17 Δlog₁₀ cfu/lungs, <i>P</i> < 0.001; 2 mg/L, -3.41 ± 0.31 Δ log₁₀ cfu/lungs versus -2.71 ± 0.37 Δlog₁₀ cfu/lungs, <i>P</i> = 0.027). No significant difference in antimicrobial activity was observed against the <i>S. pneumoniae</i> isolate with a MIC of 4 mg/L between the two regimens (-0.33 ± 0.18 Δlog₁₀ cfu/lungs versus -0.42 ± 0.37 Δlog₁₀ cfu/lungs, <i>P</i> = 0.684).</p><p><strong>Conclusion: </strong>2 g once-daily regimen of ceftriaxone is more effective for treating pneumonia caused by <i>S. pneumoniae,</i> with MICs of ≤2 mg/L.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic resistance in <i>Mycobacterium tuberculosis</i> alters tolerance to cell wall-targeting inhibitors.","authors":"William J Jowsey, Gregory M Cook, Matthew B McNeil","doi":"10.1093/jacamr/dlae086","DOIUrl":"10.1093/jacamr/dlae086","url":null,"abstract":"<p><strong>Background: </strong>A limited ability to eliminate drug-resistant strains of <i>Mycobacterium tuberculosis</i> is a major contributor to the morbidity of TB. Complicating this problem, little is known about how drug resistance-conferring mutations alter the ability of <i>M. tuberculosis</i> to tolerate antibiotic killing. Here, we investigated if drug-resistant strains of <i>M. tuberculosis</i> have an altered ability to tolerate killing by cell wall-targeting inhibitors.</p><p><strong>Methods: </strong>Bacterial killing and MIC assays were used to test for antibiotic tolerance and synergy against a panel of drug-resistant <i>M. tuberculosis</i> strains.</p><p><strong>Results: </strong>Our results demonstrate that vancomycin and thioacetazone exhibit increased killing of diverse drug-resistant strains. Mutations in <i>mmaA4</i> and <i>mmpL3</i> increased vancomycin killing, which was consistent with vancomycin synergizing with thioacetazone and MmpL3-targeting inhibitors. In contrast, mutations in the <i>mce1</i> operon conferred tolerance to vancomycin.</p><p><strong>Conclusions: </strong>Overall, this work demonstrates how drug-resistant strains experience perturbations in cell-wall production that alters their tolerance to killing by cell wall-targeting inhibitors.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}