Antimicrobial Agents and Chemotherapy最新文献

{"title":"Adaptive evolution of extensive drug resistance and persistence in epidemic ST11 KPC-producing <i>Klebsiella pneumoniae</i> during antimicrobial chemotherapy.","authors":"Tinghua Li, Yiwei Zhu, Guoxiu Xiang, Ziyang Xu, Haihui Yang, Min Li, Zhen Shen","doi":"10.1128/aac.01235-24","DOIUrl":"https://doi.org/10.1128/aac.01235-24","url":null,"abstract":"<p><p>The global rise of carbapenem-resistant <i>Klebsiella pneumoniae</i>, including strains producing <i>K. pneumoniae</i> carbapenemase (KPC) types, poses a significant public health challenge due to their resistance to critical antibiotics. Treatment options for infections caused by KPC-producing <i>K. pneumoniae</i> (KPC-KP) are increasingly limited, particularly as these strains develop resistance to last-line antibiotics such as ceftazidime/avibactam and colistin. This study investigates the evolution of antibiotic resistance and persistence in a series of clonally related ST11 KPC-KP strains isolated from a single patient undergoing extended antimicrobial treatment. The patient, a 47-year-old male with a history of kidney transplantation, developed multiple KPC-KP lung infections during his hospital stay. Resistance to colistin and ceftazidime/avibactam emerged during treatment with these antibiotics. Key resistance mechanisms identified included the integration of IS<i>Kpn26</i> into <i>mgrB</i> gene, leading to <i>mgrB</i> inactivation and colistin resistance, and the emergence of novel <i>bla</i>_KPC-2 variants (<i>bla</i>_KPC-71 and <i>bla</i>_KPC-179) that confer resistance to ceftazidime/avibactam. Despite the development of colistin resistance in a ceftazidime/avibactam-resistant KPC-KP strain following combination therapy, the patient's clinical condition significantly improved. Phenotypic assays showed that <i>mgrB</i> disruption in KPC-KP resulted in increased biofilm formation and higher susceptibility to phagocytosis. In mouse models, KPC-KP strains with <i>mgrB</i> disruption showed reduced virulence, increased lung colonization and persistence, and a lower inflammatory response, suggesting that <i>mgrB</i> disruption facilitates the transition from acute infection to colonization. This study highlights the complex interplay between antibiotic resistance and bacterial fitness, offering insights into why some patients experience clinical improvement despite severe drug resistance and incomplete bacterial clearance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0123524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in the type A <i>blaZ</i> gene as determinants of the cefazolin inoculum effect in <i>Staphylococcus aureus</i>.","authors":"Shinwon Lee, Sohee Park, Jeong Nam Kim, Soon Ok Lee, Jeong Eun Lee, Sun Hee Lee","doi":"10.1128/aac.01106-24","DOIUrl":"https://doi.org/10.1128/aac.01106-24","url":null,"abstract":"<p><p>Plasmids containing the wild-type (WT) or mutant type A <i>blaZ</i> (<i>blaZ</i>_A) gene (mutations at codons 226, 229, or both 226 and 229) were constructed and transformed into <i>Staphylococcus aureus</i> RN4220, yielding the strains WT-blaZ, M226-blaZ, M229-blaZ, and MB-blaZ. The high-inoculum cefazolin MIC was significantly lower in MB-blaZ and M226-blaZ than in WT-blaZ but not in M229-blaZ, suggesting that the single nucleotide polymorphism at codon 226 in <i>blaZ</i>_A contributes to the cefazolin inoculum effect.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0110624"},"PeriodicalIF":4.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants.","authors":"Michael Watkins, Yali Zhu, David C Griffith, Jeffery S Loutit, David Margolis, Peidi Gu","doi":"10.1128/aac.01288-24","DOIUrl":"https://doi.org/10.1128/aac.01288-24","url":null,"abstract":"<p><p>BRII-693 is a next-generation intravenous (IV)-administered synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This single-center, randomized, double-blind, placebo-controlled phase 1 study investigated the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of BRII-693 in 104 healthy participants. In single-dose cohorts, 10-400 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort. In the 7-day repeat-dose cohorts, 100-200 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort. In two 14-day repeat-dose cohorts, 150 mg of BRII-693 was evaluated in 12 participants (10 active, two placebo) each of non-Chinese and Chinese descent. No participant reported a severe or serious adverse event (AE) or an AE leading to death. Across all cohorts and for non-Chinese and Chinese participants, most AEs were mild. C_max and area under the concentration-time curve (AUC) increased in a dose-proportional manner over the dose range of single- and repeat-dosing. Mean <i>t</i>_1/2 was 2.58-4.37 hours and generally similar across single doses. An accumulation of exposure was observed following multiple doses with an accumulation ratio of 1.5 to 1.7 which was within the expected 1.3 to 2.5 range at steady state. Mean total clearance (CL) was similar between single and multiple dose administration, suggesting time-independent pharmacokinetics (PK). PK exposure was statistically equivalent between non-Chinese and Chinese participants. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of BRII-693 in healthy non-Chinese and Chinese participants.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04808414.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0128824"},"PeriodicalIF":4.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of telacebec to novel drug regimens in a murine tuberculosis model.","authors":"Oliver D Komm, Sandeep Tyagi, Andrew Garcia, Deepak Almeida, Yong Chang, Si-Yang Li, Jennie Ruelas Castillo, Paul J Converse, Todd Black, Nader Fotouhi, Eric L Nuermberger","doi":"10.1128/aac.00962-24","DOIUrl":"https://doi.org/10.1128/aac.00962-24","url":null,"abstract":"<p><p>The clinical efficacy of combination drug regimens containing the first-generation diarylquinoline (DARQ) bedaquiline in the treatment of multidrug-resistant tuberculosis has validated ATP synthesis as a vulnerable pathway in <i>Mycobacterium tuberculosis</i>. New DARQs in clinical development may be even more effective than bedaquiline, including against emerging bedaquiline-resistant strains. Telacebec (T) is a novel cytochrome bc₁:aa₃ oxidase inhibitor that also inhibits ATP synthesis. Based on its demonstrated efficacy as a monotherapy in mice and in a phase 2a clinical trial, we tested the contribution of T to novel combination therapies against two strains of <i>M. tuberculosis</i> (H37Rv and HN878) in an established BALB/c mouse model of tuberculosis in an effort to find more effective regimens. Overall, T was more effective in regimens against the HN878 strain than against the H37Rv strain, a finding supported by the greater vulnerability of the former strain to T and to genetic depletion of QcrB. Against both strains, combinations of a DARQ, clofazimine, and T were highly bactericidal. However, only against HN878 did T contribute synergistically, whereas an antagonistic effect was observed against H37Rv. These results demonstrate the therapeutic potential of T and highlight how differences in the susceptibility of <i>M. tuberculosis</i> strains could lead to different conclusions about a drug's potential contribution to novel drug regimens.CLINICAL TRIALSThis study is registered with Clinicaltrials.gov as NCT04890535 and NCT06058299.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0096224"},"PeriodicalIF":4.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and genomic analysis of the highly virulent <i>Acinetobacter baumannii</i> ST1791 strain dominating in Anhui, China.","authors":"Zhien He, Yi Huang, Wei Li, Huanhuan Zhang, Ruobing Cao, Md Roushan Ali, Yuanyuan Dai, Huaiwei Lu, Wanying Wang, Qiuhong Niu, Baolin Sun, Yujie Li","doi":"10.1128/aac.01262-24","DOIUrl":"https://doi.org/10.1128/aac.01262-24","url":null,"abstract":"<p><p>The multidrug-resistant <i>Acinetobacter baumannii</i> clonal complex 92 is spreading worldwide due to its high-frequency gene mutation and recombination, posing a significant threat to global medical and health safety. Between November 2021 and April 2022, a total of 132 clinical <i>A. baumannii</i> isolates were collected from a tertiary hospital in China. Their growth ability and virulence of these isolates were assessed using growth curve analyses and the <i>Galleria mellonella</i> infection model. The genetic characteristics of the isolates were further examined through whole-genome sequencing. ST1791^O/ST2^P isolates represented the largest proportion of isolates in our collection and exhibited the highest growth rate and strongest virulence among all sequence types (STs) analyzed. Whole-genome sequences from 14,159 clinical isolates were collected from the National Center for Biotechnology Information database, and only nine ST1791^O/ST2^P isolates were detected. Comparative genomic analysis revealed that ST1791^O/ST2^P carried 11 unique genes, 5 of which were located within the capsular polysaccharide synthesis (<i>cps</i>) gene cluster. Single nucleotide polymorphisms (SNPs) between ST1791^O/ST2^P and other isolates were primarily found in the cps gene cluster. Among the other isolates, ST195^O/ST2^P and ST208^O/ST2^P exhibited the smallest SNP differences from ST1791^O/ST2^P, while ST195^O/ST2^P and ST1486^O/ST2^P had high homology. The ST1791^O/ST2^P strain in Anhui, China, displayed significant homology with ST195^O/ST2^P, ST208^O/ST2^P, and ST1486^O/ST2^P isolates. Compared to other isolates in this study, ST1791^O/ST2^P exhibited strong growth ability and virulence. Therefore, preventing the further spread of ST1791^O/ST2^P should be a top public health priority.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0126224"},"PeriodicalIF":4.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel methionyl-tRNA synthetase inhibitor targeting gram-positive bacterial pathogens.","authors":"Nora M R Molasky, Zhongsheng Zhang, J Robert Gillespie, John Domagala, Dawn Reyna, Elke Lipka, Erkang Fan, Frederick S Buckner","doi":"10.1128/aac.00745-24","DOIUrl":"10.1128/aac.00745-24","url":null,"abstract":"<p><p>New antibiotics are needed to treat gram-positive bacterial pathogens. <b>MRS-2541</b> is a novel inhibitor of methionyl-tRNA synthetase with selective activity against gram-positive bacteria. The minimum inhibitory concentrations (MICs) against <i>Staphylococcus aureus, Streptococcus pyogenes,</i> and <i>Enterococcus</i> species range from 0.063 to 0.5 µg/mL. Given orally to mice at 50 mg/kg every 8 hours, <b>MRS-2541</b> shows sustained plasma levels well above these MICs. In the mouse thigh infection model, <b>MRS-2541</b> decreased methicillin-resistant <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i> bacterial loads to the same degree as linezolid. <b>MRS-2541</b> is a promising new antibiotic for development against skin and soft tissue infections.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0074524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different carbapenemase and siderophore production on cefiderocol susceptibility in <i>Klebsiella pneumoniae</i>.","authors":"Chengcheng Yang, Liang Wang, Jingnan Lv, Yicheng Wen, Qizhao Gao, Feinan Qian, Xiangxiang Tian, Jie Zhu, Zhichen Zhu, Liang Chen, Hong Du","doi":"10.1128/aac.01019-24","DOIUrl":"10.1128/aac.01019-24","url":null,"abstract":"<p><p>The resistance mechanism of Gram-negative bacteria to the siderophore antibiotic cefiderocol is primarily attributed to carbapenemase and siderophore uptake pathways; however, specific factors and their relationships remain to be fully elucidated. Here, we constructed cefiderocol-resistant <i>Klebsiella pneumoniae</i> (CRKP) strains carrying different carbapenemases and knocked out siderophore genes to investigate the roles of various carbapenemases and siderophores in the development of cefiderocol resistance. Antimicrobial susceptibility testing revealed that both <i>bla</i>_NDM and <i>bla</i>_KPC significantly increased the minimum inhibitory concentration (MIC) of <i>Klebsiella pneumoniae</i> (KP) to cefiderocol, while <i>bla</i>_OXA-48 showed a modest increase. Notably, KP expressing NDM exhibited a higher cefiderocol MIC compared to KP expressing KPC, although expression of NDM alone did not induce cefiderocol resistance. Laboratory evolutionary experiments demonstrated that combining pNDM with mutations in the siderophore uptake receptor gene <i>cirA</i> and pKPC with a mutation in the two-component system gene <i>envZ</i> led to KP reaching a high level of cefiderocol resistance. Although combining pOXA with mutations in the two-component system gene <i>baeS</i> did not induce cefiderocol resistance, it significantly reduced susceptibility. Moreover, siderophores could influence the development of cefiderocol resistance. Strains deficient in enterobactin exhibited increased susceptibility to cefiderocol, while deficiencies in yersiniabactin and salmochelin showed no significant alterations. In conclusion, carbapenemase gene expression facilitates cefiderocol resistance, but its presence alone is insufficient. Cefiderocol resistance in CRKP typically involves abnormal expression of certain genes and other factors, such as mutations in siderophore uptake receptor genes and two-component system genes. The enterobactin siderophore synthesis gene <i>entB</i> may also contribute to resistance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0101924"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural network-based predictions of antimicrobial resistance phenotypes in multidrug-resistant <i>Acinetobacter baumannii</i> from whole genome sequencing and gene expression.","authors":"Huiqiong Jia, Xinyang Li, Yilu Zhuang, Yuye Wu, Shasha Shi, Qingyang Sun, Fang He, Shanyan Liang, Jianfeng Wang, Mohamed S Draz, Xinyou Xie, Jun Zhang, Qing Yang, Zhi Ruan","doi":"10.1128/aac.01446-24","DOIUrl":"10.1128/aac.01446-24","url":null,"abstract":"<p><p>Whole genome sequencing (WGS) potentially represents a rapid approach for antimicrobial resistance genotype-to-phenotype prediction. However, the challenge still exists to predict fully minimum inhibitory concentrations (MICs) and antimicrobial susceptibility phenotypes based on WGS data. This study aimed to establish an artificial intelligence-based computational approach in predicting antimicrobial susceptibilities of multidrug-resistant <i>Acinetobacter baumannii</i> from WGS and gene expression data. Antimicrobial susceptibility testing (AST) was performed using the broth microdilution method for 10 antimicrobial agents. <i>In silico</i> multilocus sequence typing (MLST), antimicrobial resistance genes, and phylogeny based on cgSNP and cgMLST strategies were analyzed. High-throughput qPCR was performed to measure the expression level of antimicrobial resistance (AMR) genes. Most isolates exhibited a high level of resistance to most of the tested antimicrobial agents, with the majority belonging to the IC2/CC92 lineage. Phylogenetic analysis revealed undetected transmission events or local outbreaks. The percentage agreements between AMR phenotype and genotype ranged from 70.08% to 89.96%, with the coefficient of agreement (κ) extending from 0.025 and 0.881. The prediction of AST employed by deep neural network models achieved an accuracy of up to 98.64% on the testing data set. Additionally, several linear regression models demonstrated high prediction accuracy, reaching up to 86.15% within an error range of one gradient, indicating a linear relationship between certain gene expressions and the corresponding antimicrobial MICs. In conclusion, neural network-based predictions could be used as a tool for the surveillance of antimicrobial resistance in multidrug-resistant <i>A. baumannii</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0144624"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice.","authors":"Sabrina Mendes, Lays Cordeiro Guimarães, Pedro Augusto Carvalho Costa, Clara Couto Fernandez, Maria Marta Figueiredo, Mauro Martins Teixeira, Robson Augusto Souza Dos Santos, Pedro Pires Goulart Guimarães, Frédéric Frézard","doi":"10.1128/aac.00835-24","DOIUrl":"10.1128/aac.00835-24","url":null,"abstract":"<p><p>To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0083524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term clinical course of <i>Mycobacterium avium</i> complex pulmonary disease patients with treatment failure.","authors":"Sungmin Zo, Junsu Choe, Dae Hun Kim, Su-Young Kim, Byung Woo Jhun","doi":"10.1128/aac.01055-24","DOIUrl":"10.1128/aac.01055-24","url":null,"abstract":"<p><p>Despite guideline-based therapy, some patients with <i>Mycobacterium avium</i> complex pulmonary disease (MAC-PD) experience treatment failure. We analyzed the clinical courses of 271 patients with treatment-refractory MAC-PD who discontinued therapy after at least 12 months. Patients were categorized into two groups-the retreatment group, who resumed antibiotics due to clinical or radiological deterioration, and the stable group, who did not require antibiotics. Of the study patients, 138 (51%) were in the retreatment group, whereas 133 (49%) were in the stable group. In the multivariate analysis models, an elevated erythrocyte sedimentation rate (adjusted hazard ratio [aHR] =1.01), the presence of a cavity (aHR = 1.75), and the number of lobes affected by bronchiectasis (aHR = 1.21) were associated with the need for retreatment. Our data indicated that approximately 50% of the patients with refractory MAC-PD who discontinued antibiotics eventually required retreatment, which was influenced by the extent of lung destruction or inflammation. These findings can aid in determining treatment strategies for patients with refractory diseases.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0105524"},"PeriodicalIF":4.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}