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
Received 13 August 2018
Accepted for publication 14 November 2018
Published 28 December 2018 Volume 2019:12 Pages 95—104
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Joachim Wink
Feng Wang,1,* Jingwei Liu,2,* Hongye Liu,2 Jing Huang,1 Shaochun Chen,2 Xiangsheng Chen,2 Yueping Yin2
1Department of STD Control Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, China; 2Department of Reference STD Lab, National Center for STD Control, Chinese Center for Disease Control and Prevention, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
*These authors contributed equally to this work
Background: Neisseria gonorrhoeae resistance to azithromycin has become a significant public health concern globally, and high-level azithromycin-resistant (HL-AzmR) isolates have emerged frequently. However, high-level azithromycin resistance is considered to be caused by mutated alleles of 23S rRNA gene at position 2059, and identification of HL-AzmR isolates mainly relies on agar dilution method or E-test method. This study aimed to assess the accuracy of the molecular assays targeting the mutation A2059G for identifying HL-AzmR isolates and thereby determine the association between the mutation and high-level azithromycin resistance.
Methods: Two researchers independently searched six databases to identify studies published from the launch of each database to October 15, 2017. The fixed effects model was used to estimate the pooled sensitivity rate, specificity rate, positive predictive value (PPV), and negative predictive value (NPV). Summary receiver operating characteristic curves were generated, and the area under the curve (AUC) was determined to estimate the overall performance of the assays. The Deeks’ test was conducted to evaluate potential publication bias.
Results: Ten relevant studies were included in the meta-analysis to assess the synthetic accuracy of the molecular assays. The molecular assays had the synthetic sensitivity rate of 97.8% and the synthetic specificity rate of 99.1%. And the aggregated PPV and NPV were 96.4% and 99.5%, respectively. AUC was 0.99, suggesting a close relation existing between the mutation A2059G and high-level azithromycin resistance. This indicated that the molecular assays targeting the mutation A2059G have relatively high overall accuracy for identifying HL-AzmR N. gonorrhoeae isolates. Publication bias was statistically significant.
Conclusion: The mutation A2059G is the critical factor causing high-level azithromycin resistance. Hence, molecular methods are recommended to be put into clinical practice by commercialization, which will assist clinicians to prescribe more precisely.
Keywords: Neisseria gonorrhoeae, 23S rRNA, A2059G, azithromycin resistance, systematic review
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