收稿日期: 2025-08-18
修回日期: 2025-09-12
录用日期: 2025-09-30
网络出版日期: 2026-04-13
基金资助
广东省科技计划项目(2020B1111170014);广东省感染性疾病（结核病）临床医学研究中心(2020B1111170014);广东省医学科学技术研究基金项目(A2023059)
Mechanisms of drug resistance， clinical drug susceptibility testing， and advances in treatment of Mycobacterium abscessus
Received date: 2025-08-18
Revised date: 2025-09-12
Accepted date: 2025-09-30
Online published: 2026-04-13
脓肿分枝杆菌复合群（Mycobacterium abscessus complex，MABC）是临床最常见的致病性快速生长非结核分枝杆菌，尤其易累及呼吸道，其快速生长和显著的亚种间耐药差异导致耐药感染治疗困难。本文综述MABC分子耐药机制，包括erm（41）基因介导的诱导性大环内酯耐药、rrl基因突变导致的获得性大环内酯耐药，以及氨基糖苷类药物耐药的靶点突变、修饰酶灭活及外排泵等机制，阐述亚种耐药差异及地理分布特点；总结临床药敏检测原则，强调亚种鉴定与表型、分子分型的整合应用；结合研究进展介绍耐药性MABC感染的多药联合治疗策略及试验性治疗手段，为临床精准诊断与个体化治疗提供参考，助力提升耐药性MABC感染诊治水平。
赖晓宇 , 陈珣珣 , 廖庆华 , 余美玲 , 郭卉欣 , 王嘉雯 , 陈瑜晖 , 温文沛 . 脓肿分枝杆菌耐药机制、临床药敏检测及治疗研究进展[J]. 实用医学杂志, 2026 , 42(7) : 1134 -1141 . DOI: 10.3969/j.issn.1006-5725.2026.07.003
The Mycobacterium abscessus complex （MABC） stands as the most prevalent clinically pathogenic rapidly-growing nontuberculous mycobacterium， with a distinct preference for the respiratory tract. Its rapid growth and substantial disparities in drug resistance among subspecies make the treatment of drug-resistant infections arduous. This article conducts a comprehensive review of the molecular mechanisms of drug resistance in MABC. These mechanisms include erm（41）-mediated inducible macrolide resistance， acquired macrolide resistance resulting from rrl gene mutations， and the mechanisms behind aminoglycoside resistance， such as target mutations， inactivation by modifying enzymes， and efflux pumps. It further details the subspecies-specific differences in drug resistance and the characteristics of geographical distribution. Moreover， it summarizes the principles of clinical drug susceptibility testing， highlighting the integrated application of subspecies identification， phenotypic detection， and molecular typing. Integrating the latest research advances， it presents multidrug combination therapy strategies and experimental therapeutic approaches for drug-resistant MABC infections. The aim is to offer references for clinical precision diagnosis and individualized treatment， and to contribute to enhancing the level of diagnosis and treatment of drug-resistant MABC infections.
| [1] | MATSUMOTO Y， KINJO T， MOTOOKA D， et al. Comprehensive subspecies identification of 175 nontuberculous mycobacteria species based on 7547 genomic profiles［J］. Emerg Microbes Infect， 2019， 8（1）： 1043-1053. doi： 10.1080/22221751.2019.1637702 . |
| [2] | YANG T， BEACH K E， ZHU C， et al. Genomic Analysis of Global Mycobacterium abscessus Isolates Reveals Ongoing Evolution of Drug Resistance-Associated Genes［J］. J Infect Dis， 2025， 231（5）： 1150-1154. doi： 10.1093/infdis/jiae580 . |
| [3] | HOU Y， PI R， JIA J， et al. Limited predictive power of known resistance genes for phenotypic drug resistance in clinical Mycobacterium abscessus complex from Beijing in China［J］. Antimicrob Agents Chemother， 2025， 69（7）： e0184724. doi： 10.1128/aac.01847-24 . |
| [4] | NASH K A， BROWN-ELLIOTT B A， WALLACE R J. A novel gene， erm （41）， confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae［J］. Antimicrob Agents Chemother， 2009， 53 （4）： 1367-1376. doi： 10.1128/AAC.01275-08 . |
| [5] | RICHARD M， GUTIéRREZ A V， KREMER L. Dissecting erm （41）-Mediated Macrolide-Inducible Resistance in Mycobacterium abscessus［J］. Antimicrob Agents Chemother， 2020， 64（2）： e01879. doi： 10.1128/AAC.01879-19 . |
| [6] | CARVALHO N F G， PAVAN F， SATO D N， et al. Genetic correlates of clarithromycin susceptibility among isolates of the Mycobacterium abscessus group and the potential clinical applicability of a PCR-based analysis of erm （41）［J］. J Antimicrob Chemother， 2018， 73（4）： 862-866. doi： 10.1093/jac/dkx476 . |
| [7] | WANG X， SU B， CHEN P， et al. Subspecies distribution and drug-resistance characteristics of Mycobacterium abscessus complex clinical isolates in South China［J］. Microbiol Spectr， 2025， 13（5）： e0410323. doi： 10.1128/spectrum.04103-23 . |
| [8] | YOSHIDA M， CHIEN J Y， MORIMOTO K， et al. Molecular Epidemiological Characteristics of Mycobacterium abscessus Complex Derived from Non-Cystic Fibrosis Patients in Japan and Taiwan［J］. Microbiol Spectr， 2022， 10（3）： e0057122. doi： 10.1128/spectrum.00571-22 . |
| [9] | BUENESTADO-SERRANO S， MARTíNEZ-LIROLA M， HERRANZ-MARTíN M， et al.Microevolution， reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus［J］. Nat Commun， 2024， 15（1）： 2717. doi： 10.1038/s41467-024-46552-w . |
| [10] | SHALLOM S J， ZELAZNY A M. Detection of Mixed Populations of Clarithromycin-Susceptible and Resistant Mycobacterium abscessus Strains［J］. J Clin Microbiol， 2022， 60（4）： e0169421. doi： 10.1128/jcm.01694-21 . |
| [11] | SHARMA M K， LA Y， JANELLA D， et al. A real-time PCR assay for rapid identification of inducible and acquired clarithromycin resistance in Mycobacterium abscessus［J］. BMC Infect Dis， 2020， 20（1）： 944.doi： 10.1186/s12879-020-05686-0 . |
| [12] | MWANGI Z， NAEKU G， MUREITHI M， et al.Mutation patterns of resistance genes for macrolides， aminoglycosides， and rifampicin in non-tuberculous mycobacteria isolates from Kenya［J］. F1000 Res， 2023， 11： 962. doi： 10.12688/f1000research.124002.5 . |
| [13] | LI X， ZHU Y， LU Y， et al. Population genetic analysis of clinical Mycobacterium abscessus complex strains in China［J］. Front Cell Infect Microbiol， 2025， 14： 1496896. doi： 10.3389/fcimb.2024.1496896 . |
| [14] | RUEDAS-LóPEZ A， TATO M， BRONCANO-LAVADO A， et al. Subspecies Distribution and Antimicrobial Susceptibility Testing of Mycobacterium abscessus Clinical Isolates in Madrid， Spain： A Retrospective Multicenter Study［J］. Microbiol Spectr， 2023， 11（3）： e0504122. doi： 10.1128/spectrum.05041-22 . |
| [15] | MAURER F P， RüEGGER V， RITTER C， et al. Acquisition of clarithromycin resistance mutations in the 23S rRNA gene of Mycobacterium abscessus in the presence of inducible erm （41）［J］. J Antimicrob Chemother， 2012， 67（11）： 2606-2611. doi： 10.1093/jac/dks279 . |
| [16] | YOSHIDA S， TSUYUGUCHI K， KOBAYASHI T， et al.Comparison of drug-susceptibility patterns and gene sequences associated with clarithromycin and azithromycin resistance in Mycobacterium abscessus complex isolates and evaluation of the accumulation of intrinsic macrolide resistance［J］. J Med Microbiol， 2021， 70（3）. doi： 10.1099/jmm.0.001326 . |
| [17] | JONG B E， WU T S， CHEN N Y， et al.Impact on Macrolide Resistance of Genetic Diversity of Mycobacterium abscessus Species［J］. Microbiol Spectr， 2022， 10（6）： e0274922. doi： 10.1128/spectrum.02749-22 . |
| [18] | LI H， MULATI G， SHANG Y， et al. Rapid Detection of Clarithromycin and Amikacin Resistance in Mycobacterium abscessus Complex by High-Resolution Melting Curve Analysis［J］. Microbiol Spectr， 2022， 10（3）： e0057422. doi： 10.1128/spectrum.00574-22 . |
| [19] | SUKMONGKOLCHAI S， PETSONG S， OUDOMYING N， et al.Clinical characteristics and drug susceptibility profiles of Mycobacterium abscessus complex infection at a medical school in Thailand［J］. Ann Clin Microbiol Antimicrob， 2023， 22（1）： 87. doi： 10.1186/s12941-023-00637-4 . |
| [20] | CHOI H， KIM S Y， KIM D H， et al. Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease［J］. Antimicrob Agents Ch， 2017， 61（10）： e01146. doi： 10.1128/AAC.01146-17 . |
| [21] | DING J， HAMEED H M A， LONG L， et al.Correlation between rrs gene mutations and amikacin resistance in Mycobacterium abscessus： Implications for fitness cost and clinical prevalence［J］. J Antimicrob Chemother， 2025， 80（3）： 746-751. doi： 10.1093/jac/dkae468 . |
| [22] | ZHANG Z， WANG W， WANG Y， et al.Inducible Resistance to Amikacin in Mycobacterium abscessus Isolated in Beijing， China［J］. Infect Drug Resist， 2022， 15： 2287-2291. doi： 10.2147/IDR.S357887 . |
| [23] | PRAMMANANAN T， SANDER P， BROWN B A， et al.A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae［J］. J Infect Dis， 1998， 177（6）： 1573-1581. doi： 10.1086/515328 . |
| [24] | MAURER F P， BRUDERER V L， CASTELBERG C， et al. Aminoglycoside-modifying enzymes determine the innate susceptibility to aminoglycoside antibiotics in rapidly growing mycobacteria［J］. J Antimicrob Chemother， 2015， 70（5）： 1412-1419. doi： 10.1093/jac/dku550 . |
| [25] | BRYANT J M， GROGONO D M， GREAVES D， et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis： A retrospective cohort study［J］. Lancet， 2013， 381（9877）： 1551-1560. doi： 10.1016/S0140-6736（13）60632-7 . |
| [26] | NESSAR R， CAMBAU E， REYRAT J M， et al. Mycobacterium abscessus： A new antibiotic nightmare［J］. J Antimicrob Chemother， 2012， 67（4）： 810-818. doi： 10.1093/jac/dkr578 . |
| [27] | DALEY C L， IACCARINO J M， LANGE C， et al. Treatment of nontuberculous mycobacterial pulmonary disease： An official ATS/ERS/ESCMID/IDSA clinical practice guideline［J］. Eur Respir J， 2020， 56（1）： 2000535. doi： 10.1183/13993003.00535-2020 . |
| [28] | HAWORTH C S， BANKS J， CAPSTICK T， et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease （NTM-PD）［J］. Thorax， 2017， 72（）： ii1-ii64. doi： 10.1136/thoraxjnl-2017-210927 . |
| [29] | BROWN-ELLIOTT B A， VASIREDDY S， VASIREDDY R， et al. Utility of sequencing the erm （41） gene in isolates of Mycobacterium abscessus subsp. abscessus with low and intermediate clarithromycin MICs［J］. J Clin Microbiol， 2015， 53（4）： 1211-1215. doi： 10.1128/JCM.02950-14 . |
| [30] | GRIFFITH D E， Daley C L. Treatment of Mycobacterium abscessus Pulmonary Disease［J］. Chest， 2022， 16（1）： 64-75. doi： 10.1128/JCM.02950-14 . |
| [31] | FLOTO R A， OLIVIER K N， SAIMAN L， et al.US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis： executive summary［J］. Thorax， 2016， 71（1）： 88-90. doi： 10.1136/thoraxjnl-2015-207983 . |
| [32] | NEGATU D A， GONZáLEZ DEL RíO R， CACHO-IZQUIERDO M， et al. Activity of Oral Tebipenem-Avibactam in a Mouse Model of Mycobacterium abscessus Lung Infection［J］. Antimicrob Agents Chemother， 2023， 67（2）： e0145922. doi： 10.1128/aac.01459-22 . |
| [33] | LE MOIGNE V， BITAR M， ARTHUR M， et al. The addition of amoxicillin improves the efficacy of the imipenem-avibactam combination against Mycobacterium abscessus in a mouse model of infection［J］. Antimicrob Agents Chemother， 2025， 69（8）： e0053425. doi： 10.1128/aac.00534-25 . |
| [34] | DOUSA K M， KURZ S G， TARACILA M A， et al. Insights into the l，d-Transpeptidases and d，d-Carboxypeptidase of Mycobacterium abscessus： Ceftaroline， Imipenem， and Novel Diazabicyclooctane Inhibitors［J］. Antimicrob Agents Chemother， 2020， 64（8）： e00098. doi： 10.1128/AAC.00098-20 . |
| [35] | LONGO B M， TRUNFIO M， CALCAGNO A. Dual β-lactams for the treatment of Mycobacterium abscessus： A review of the evidence and a call to act against an antibiotic nightmare［J］. J Antimicrob Chemother， 2024， 79（11）： 2731-2741. doi： 10.1093/jac/dkae288 . |
| [36] | BEECH A J， WEINBERG S E， MORTIMER A E， et al. Mycobacterium abscessus skin and soft tissue infection following autologous fat grafting in Kurdistan treated with an antibiotic combination including Imipenem-Relebactam and Rifabutin［J］. J Clin Tuberc Other Mycobact Dis， 2023， 32： 100381. doi： 10.1016/j.jctube.2023.100381 . |
| [37] | VOGIATZOGLOU A I， HADJI ΜITROVA M， PAPADAKI E， et al.Combination of Imipenem-Cilastatin-Relebactam and Amoxicillin in the Antibiotic Regimen in Two Cases of Mycobacterium abscessus Lung Infection［J］. Cureus， 2024， 16（7）： e65112. doi： 10.7759/cureus.65112 . |
| [38] | YAMATANI I， AONO A， FUJIWARA K， et al.In vitro effects of the new oral β-lactamase inhibitor xeruborbactam in combination with oral β-lactams against clinical Mycobacterium abscessus isolates［J］. Microbiol Spectr， 2024， 12（7）： e0008424. doi： 10.1128/spectrum.00084-24 . |
| [39] | STORY-ROLLER E， GALANIS C， LAMICHHANE G.β-Lactam combinations that exhibit synergy against Mycobacteroides abscessus clinical isolates［J］. Antimicrob Agents Chemother， 2021， 65（10）： e02545-20. doi： 10.1128/AAC.02545-20 . |
| [40] | STORY-ROLLER E， MAGGIONCALDA E C， LAMICHHANE G.Synergistic efficacy of β-lactam combinations against Mycobacterium abscessus pulmonary infection in mice［J］. Antimicrob Agents Chemother， 2019， 63（8）： e00614-19. doi： 10.1128/AAC.00614-19 . |
| [41] | DOUSA K M， KURZ S G， TARACILA M A，et al. Insights into the L，D-transpeptidases and D，D-carboxypeptidase of Mycobacterium abscessus： Ceftaroline， imipenem， and novel diazabicyclooctane inhibitors［J］. Antimicrob Agents Chemother， 2020， 64（8）： e00098-20. doi： 10.1128/AAC.00098-20 . |
| [42] | PEARSON J C， DIONNE B， RICHTERMAN A， et al. Omadacycline for the Treatment of Mycobacterium abscessus Disease： A Case Series［J］. Open Forum Infect Dis， 2020， 7（10）： ofaa415. doi： 10.1093/ofid/ofaa415 . |
| [43] | FILE T M， RAMIREZ J A， WILDE A M. New Perspectives on Antimicrobial Agents： Omadacycline for community-acquired pneumonia， skin and soft tissue infections， and nontuberculous mycobacteria （focus on M. abscessus）［J］. Antimicrob Agents Chemother， 2025， 69（2）： e0108724. doi： 10.1128/aac.01087-24 . |
| [44] | 王宇津， 荆玮， 李强， 等. 康替唑胺对脓肿分枝杆菌的抗菌活性研究［J］. 中国医刊， 2024， 59（9）： 1026-1028. doi： 10.3969/j.issn.1008-1070.2024.09.025 . |
| [45] | GAO X， DING C， XIE D， et al. Contezolid-Containing Regimen Successfully Treated Multiple Drug Resistance Mycobacterium Abscessus Complex Infection of Skin： A Case Report and Literature Review［J］. Infect Drug Resist， 2024， 17： 1243-1249. doi： 10.2147/IDR.S453541 . |
| [46] | COMPAIN F， SOROKA D， HEYM B， et al. In vitro activity of tedizolid against the Mycobacterium abscessus complex［J］. Diagn Microbiol Infect Dis， 2017， 90（3）： 186-189. doi： 10.1016/j.diagmicrobio.2017.11.001 . |
| [47] | BURKE A， CARTER R， TOLSON C， et al.In vitro susceptibility testing of imipenem-relebactam and tedizolid against 102 Mycobacterium abscessus isolates［J］. Int J Antimicrob Agents， 2023， 62（4）： 106938. doi： 10.1016/j.ijantimicag.2023.106938 . |
| [48] | SEKI M， KAMIOKA Y， TAKANO K， et al. Mycobacterium abscessus Associated Peritonitis with CAPD Successfully Treated Using a Linezolid and Tedizolid Containing Regimen Suggested Immunomodulatory Effects［J］. Am J Case Rep， 2020， 21： e924642. doi： 10.12659/AJCR.924642 . |
| [49] | KIM T S， CHOE J H， KIM Y J， et al. Activity of LCB01-0371， a Novel Oxazolidinone， against Mycobacterium abscessus［J］. Antimicrob Agents Chemother， 2017， 61（9）： e02752. doi： 10.1128/AAC.02752-16 . |
| [50] | COTRONEO N， STOKES S S， PUCCI M J， et al. Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection［J］. J Antimicrob Chemother， 2024， 79（4）： 875-882. doi： 10.1093/jac/dkae046 . |
| [51] | RUBINO C M， ONUFRAK N J， VAN INGEN J， et al. Population Pharmacokinetic Evaluation of Amikacin Liposome Inhalation Suspension in Patients with Treatment-Refractory Nontuberculous Mycobacterial Lung Disease［J］. Eur J Drug Metab Pharmacokinet， 2021， 46（2）： 277-287. doi： 10.1007/s13318-020-00669-7 . |
| [52] | PEARCE C Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo［J］. J Antimicrob Chemoth， 2020， 75（7）： 1889-1894. doi： 10.1093/jac/dkaa110 . |
| [53] | NICK J A， DEDRICK R M， GRAY A L， et al. Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection［J］. Cell， 2022， 185（11）： 1860-1874. doi： 10.1016/j.cell.2022.04.024 . |
| [54] | DEDRICK R M， GUERRERO-BUSTAMANTE C A， GARLENA R A， et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus［J］. Nat Med， 2019， 25（5）： 730-733. doi： 10.1093/ofid/ofac194 . |
/
| 〈 |
|
〉 |