The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis

Background: <i>Neisseria gonorrhoeae (N. gonorrhoeae)</i> is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of <i>N. gonorrhoeae</i> has become a serious public health problem. The accuracy of molecular detection for de...

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Main Authors: Qian Zhou, Jingwei Liu, Shaochun Chen, Wenqi Xu, Yan Han, Yueping Yin
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/10/9/1027
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author Qian Zhou
Jingwei Liu
Shaochun Chen
Wenqi Xu
Yan Han
Yueping Yin
author_facet Qian Zhou
Jingwei Liu
Shaochun Chen
Wenqi Xu
Yan Han
Yueping Yin
author_sort Qian Zhou
collection DOAJ
description Background: <i>Neisseria gonorrhoeae (N. gonorrhoeae)</i> is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of <i>N. gonorrhoeae</i> 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 <i>N. gonorrhoeae</i> 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 <i>N. gonorrhoeae</i> 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 2–128 mg/L or 4–128 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’ test. We included 20 studies in our study: 20 studies have data of <i>N. gonorrhoeae</i> with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of <i>N. gonorrhoeae</i> with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2–128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6–74%), the pooled specificity rate was 98.7% (95% CI, 98.2–99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4–128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9–94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1–96.6%), 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 <i>N. gonorrhoeae</i>, especially when the moderate level is set at 4–128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.
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spelling doaj.art-87cf0fdb29234adeadf4d4c79253beb62023-11-22T11:45:08ZengMDPI AGAntibiotics2079-63822021-08-01109102710.3390/antibiotics10091027The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-AnalysisQian Zhou0Jingwei Liu1Shaochun Chen2Wenqi Xu3Yan Han4Yueping Yin5National 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaBackground: <i>Neisseria gonorrhoeae (N. gonorrhoeae)</i> is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of <i>N. gonorrhoeae</i> 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 <i>N. gonorrhoeae</i> 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 <i>N. gonorrhoeae</i> 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 2–128 mg/L or 4–128 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’ test. We included 20 studies in our study: 20 studies have data of <i>N. gonorrhoeae</i> with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of <i>N. gonorrhoeae</i> with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2–128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6–74%), the pooled specificity rate was 98.7% (95% CI, 98.2–99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4–128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9–94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1–96.6%), 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 <i>N. gonorrhoeae</i>, especially when the moderate level is set at 4–128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.https://www.mdpi.com/2079-6382/10/9/1027<i>Neisseria gonorrhoeae</i>23S rRNAazithromycin resistance
spellingShingle Qian Zhou
Jingwei Liu
Shaochun Chen
Wenqi Xu
Yan Han
Yueping Yin
The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
Antibiotics
<i>Neisseria gonorrhoeae</i>
23S rRNA
azithromycin resistance
title The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
title_full The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
title_fullStr The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
title_full_unstemmed The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
title_short The Accuracy of Molecular Detection Targeting the Mutation C2611T for Detecting Moderate-Level Azithromycin Resistance in <i>Neisseria gonorrhoeae</i>: A Systematic Review and Meta-Analysis
title_sort accuracy of molecular detection targeting the mutation c2611t for detecting moderate level azithromycin resistance in i neisseria gonorrhoeae i a systematic review and meta analysis
topic <i>Neisseria gonorrhoeae</i>
23S rRNA
azithromycin resistance
url https://www.mdpi.com/2079-6382/10/9/1027
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