{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:54:31Z","timestamp":1788814471479,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Clinical Research Center","award":["2019060001"],"award-info":[{"award-number":["2019060001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Neisseria gonorrhoeae (N. gonorrhoeae) is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of N. gonorrhoeae has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the N. gonorrhoeae 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance. Methods and Findings: In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each N. gonorrhoeae isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2\u2013128 mg\/L or 4\u2013128 mg\/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks\u2019 test. We included 20 studies in our study: 20 studies have data of N. gonorrhoeae with MICs between 2 and 128 mg\/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of N. gonorrhoeae with MICs between 4 and 128 mg\/L (3367 samples). In the group with the moderate level of 2\u2013128 mg\/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6\u201374%), the pooled specificity rate was 98.7% (95% CI, 98.2\u201399.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4\u2013128 mg\/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9\u201394.2%), the pooled specificity rate was 95.9% (95% CI, 95.1\u201396.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6). Conclusion: Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in N. gonorrhoeae, especially when the moderate level is set at 4\u2013128 mg\/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.<\/jats:p>","DOI":"10.3390\/antibiotics10091027","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:43:43Z","timestamp":1629780223000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in Neisseria gonorrhoeae: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-1062","authenticated-orcid":false,"given":"Qian","family":"Zhou","sequence":"first","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-141X","authenticated-orcid":false,"given":"Jingwei","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6447-928X","authenticated-orcid":false,"given":"Shaochun","family":"Chen","sequence":"additional","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Xu","sequence":"additional","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Han","sequence":"additional","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueping","family":"Yin","sequence":"additional","affiliation":[{"name":"National Center for STD Control, Chinese Center for Disease Control and Prevention, Department of Reference STD Lab, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro.2017.169","article-title":"Neisseria gonorrhoeae host adaptation and pathogenesis","volume":"16","author":"Quillin","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","first-page":"168","article-title":"Guidelines for diagnosis and treatment of syphilis, gonorrhea and genital Chlamydia trachomatis infection (2020)","volume":"53","author":"Wang","year":"2020","journal-title":"Chin. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41572-019-0128-6","article-title":"Gonorrhoea","volume":"5","author":"Unemo","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/CMR.00010-14","article-title":"Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: Past, evolution, and future","volume":"27","author":"Unemo","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","unstructured":"World Health Organization (1990). Global Surveillance Network for Gonococcal Antimicrobial Susceptibility, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Centers for Disease Control and Prevention (2012). Update to CDC\u2019s Sexually transmitted diseases treatment guidelines, 2010: Oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR. Morb. Mortal. Wkly. Rep., 61, 590\u2013594.","DOI":"10.1016\/j.annemergmed.2012.10.014"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1258\/ijsa.2011.011267","article-title":"UK National guideline for the management of gonorrhoea in adults, 2011","volume":"22","author":"Bignell","year":"2011","journal-title":"Int. J. STD AIDS"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yin, Y.P., Han, Y., Dai, X.Q., Zheng, H.P., Chen, S.C., Zhu, B.Y., Yong, G., Zhong, N., Hu, L.H., and Cao, W.L. (2018). Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China: A retrospective study of national surveillance data from 2013 to 2016. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002499"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liang, J.Y., Cao, W.L., Li, X.D., Bi, C., Yang, R.D., Liang, Y.H., Li, P., Ye, X.D., Chen, X.X., and Zhang, X.B. (2016). Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009\u20132013): Coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1469-3"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ijantimicag.2019.08.015","article-title":"Changing antimicrobial susceptibility and molecular characterisation of Neisseria gonorrhoeae isolates in Guangdong, China: In a background of rapidly rising epidemic","volume":"54","author":"Qin","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.45.1.1-12.2001","article-title":"Macrolide resistance conferred by base substitutions in 23S rRNA","volume":"45","author":"Vester","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.7326\/0003-4819-143-2-200507190-00012","article-title":"Meta-analysis: The value of clinical assessment in the diagnosis of deep venous thrombosis","volume":"143","author":"Goodacre","year":"2005","journal-title":"Ann. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1128\/AAC.00309-10","article-title":"High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes","volume":"54","author":"Chisholm","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1128\/AAC.02608-13","article-title":"Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in neisseria gonorrhoeae in ontario, Canada","volume":"58","author":"Allen","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1093\/jac\/dkw182","article-title":"Molecular epidemiology and mechanisms of resistance of azithromycin-resistant Neisseria gonorrhoeae isolated in France during 2013\u201314","volume":"71","author":"Belkacem","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1128\/JCM.02589-14","article-title":"Whole-genome phylogenomic heterogeneity of Neisseria gonorrhoeae isolates with decreased cephalosporin susceptibility collected in Canada between 1989 and 2013","volume":"53","author":"Demczuk","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e154","DOI":"10.1016\/S2666-5247(20)30059-8","article-title":"Azithromycin susceptibility of Neisseria gonorrhoeae in the USA in 2017: A genomic analysis of surveillance data","volume":"1","author":"Gernert","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1473-3099(18)30225-1","article-title":"Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: A genomic survey","volume":"18","author":"Harris","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1093\/jac\/dkw279","article-title":"WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC > 2 mg\/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014","volume":"71","author":"Jacobsson","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijantimicag.2016.10.023","article-title":"Use of whole-genome sequencing data to analyze 23S rRNA-mediated azithromycin resistance","volume":"49","author":"Johnson","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/jac\/dkx405","article-title":"Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand","volume":"73","author":"Lee","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00773-19","DOI":"10.1128\/AAC.00773-19","article-title":"Emergence and spread of Neisseria gonorrhoeae strains with high-level resistance to azithromycin in Taiwan from 2001 to 2018","volume":"63","author":"Liu","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1093\/jac\/dkaa360","article-title":"Multiplex real-time PCR assays for the prediction of cephalosporin, ciprofloxacin and azithromycin antimicrobial susceptibility of positive Neisseria gonorrhoeae nucleic acid amplification test samples","volume":"75","author":"Peterson","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","first-page":"84","article-title":"Evaluation of the SpeeDx ResistancePlus\u00ae GC and SpeeDx GC 23S 2611 (beta) molecular assays for prediction of antimicrobial resistance\/susceptibility to ciprofloxacin and azithromycin in Neisseria gonorrhoeae","volume":"76","author":"Ronza","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1007\/s10096-018-3296-5","article-title":"Antimicrobial resistance and molecular epidemiology using whole-genome sequencing of Neisseria gonorrhoeae in Ireland, 2014\u20132016: Focus on extended-spectrum cephalosporins and azithromycin","volume":"37","author":"Ryan","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1093\/infdis\/jiz079","article-title":"Evidence of recent genomic evolution in gonococcal strains with decreased susceptibility to cephalosporins or azithromycin in the United States, 2014\u20132016","volume":"220","author":"Thomas","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_29","first-page":"3244","article-title":"Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S rRNA mutations associated with azithromycin resistance","volume":"70","author":"Trembizki","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1128\/JCM.03195-15","article-title":"Genomic epidemiology and molecular resistance mechanisms of azithromycin-resistant Neisseria gonorrhoeae in Canada from 1997 to 2014","volume":"54","author":"Walter","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e02499-17","DOI":"10.1128\/AAC.02499-17","article-title":"Increasing resistance to azithromycin in Neisseria gonorrhoeae in eastern Chinese cities: Resistance mechanisms and genetic diversity among isolates from Nanjing","volume":"62","author":"Wan","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/jac\/dky017","article-title":"Azithromycin-resistant Neisseria gonorrhoeae spreading amongst men who have sex with men (MSM) and heterosexuals in New South Wales, Australia, 2017","volume":"73","author":"Whiley","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02374-16","DOI":"10.1128\/AAC.02374-16","article-title":"A case-control study of molecular epidemiology in relation to azithromycin resistance in Neisseria gonorrhoeae isolates collected in Amsterdam, the Netherlands, between 2008 and 2015","volume":"61","author":"Wind","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","first-page":"219","article-title":"Antibiotic resistant mechanism and epidemiological characteristics of azithromycin-resistant Neisseria gonorrhoeae strains in Shenzhen","volume":"37","author":"Zhang","year":"2017","journal-title":"Chin. J. Microbiol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/IDR.S183754","article-title":"Evaluation of the accuracy of molecular assays targeting the mutation A2059G for detecting high-level azithromycin resistance in Neisseria gonorrhoeae: A systematic review and meta-analysis","volume":"12","author":"Wang","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jiac.2016.07.012","article-title":"Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility of azithromycin and increase in the failure of azithromycin therapy in male gonococcal urethritis in Sendai in 2015","volume":"22","author":"Yasuda","year":"2016","journal-title":"J. Infect. Chemother."},{"key":"ref_37","first-page":"449","article-title":"Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea: The relationship between antibiotic MIC and clinical outcome","volume":"75","author":"Cole","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Unemo, M., Ross, J., Serwin, A.B., Gomberg, M., Cusini, M., and Jensen, J.S. (2020). 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS.","DOI":"10.1177\/0956462420949126"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/9\/1027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:50:15Z","timestamp":1760165415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/9\/1027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["antibiotics10091027"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10091027","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]}}}