High prevalence of<i>Neisseria gonorrhoeae</i>with high-level resistance to azithromycin in Hangzhou, China: Table 1.

Ni, Chunshan; Xue, Juan; Zhang, Chuanling; Zhou, Haiyong; Veen, Stijn van der

doi:10.1093/jac/dkw131

Cited by 30 publications

(35 citation statements)

References 10 publications

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“…Furthermore, through the implementation of MLST and NG-MAST genotyping, it could be inferred that the AZM-HLR isolates circulating in Taiwan may originate from an internationally successful clone that evolved with spontaneous genetic events to the current variation observed in our study. China reported that AZM-HLR N. gonorrhoeae isolates belonging to NG-MAST 1866 in Hangzhou city in 2011 and 2012 carried identical AZM resistance determinants to our isolates, including the A2059G mutation, Ϫ35A deletion, and G45D mutation (18). Furthermore, in early 2018, the United Kingdom and Australia reported CRO-and AZM-resistant isolates G97687 and A2735, respectively, and they were typed as the same genotype, MLST 12039 and NG-MAST 16848 (7,8).…”

Section: Discussionmentioning

confidence: 63%

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Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018

Liu

Wang

Liao

et al. 2019

Antimicrob Agents Chemother

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A total of 598 Neisseria gonorrhoeae isolates obtained from patients in Taiwan from 2001 to 2018 were evaluated. The MICs of ceftriaxone (CRO) and azithromycin (AZM) against the isolates were determined by the agar dilution method. N. gonorrhoeae isolates with AZM MICs of ≥1 μg/ml were identified and characterized by the presence of AZM resistance determinants. For high-level AZM-resistant (AZM-HLR) isolates (MIC ≥ 256 μg/ml), genotyping was performed using multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Among the N. gonorrhoeae isolates studied, 8.7% (52/598) exhibited AZM MICs of ≥1 μg/ml. Thirteen of the 52 isolates contained A2059G (23S rRNA NG-STAR type 1) or C2611T (23S rRNA NG-STAR type 2) mutations. The prevalence of the A2059G mutation was higher in AZM-HLR isolates (P < 0.001). The −35A deletion in the promoter region of the mtrR gene did not differ between AZM-HLR isolates (100%, 10/10) and the isolates with AZM MICs of 1 μg/ml to 64 μg/ml (95.2%, 40/42) (P = 1.000). The presence of mutations in the mtrR coding region was significantly different between these two groups at 90% (9/10) and 26.2% (11/42), respectively (P < 0.001). The AZM-HLR isolates, all carrying four mutated A2059G alleles, a −35A deletion, and G45D, were classified as MLST 12039/10899 and NG-MAST 1866/16497. In conclusion, Taiwan is among the countries reporting gonococci with high-level resistance to AZM so that a single dose of 1 g ceftriaxone intramuscularly as the first choice for management of N. gonorrhoeae infection should be evaluated.

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Section: Discussionmentioning

confidence: 63%

“…Emergence of AZM-HLR N. gonorrhoeae has been described in many countries, including Argentina in 2009 (15), the United States in 2012 (16), Australia in 2015 (17), Canada in 2016 (11), China in 2016 (18), and the United Kingdom in 2018 (12). In this study, we first report the emergence and clustering of AZM-HLR N. gonorrhoeae in Taiwan.…”

Section: Discussionmentioning

confidence: 71%

Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018

Liu

Wang

Liao

et al. 2019

Antimicrob Agents Chemother

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“…The UK HL-AziR isolates from 2014 onwards were distinct from those seen previously in the UK, from the international HL-AziR N gonorrhoeae sequences available from the studies that we have previously described, [17][18][19] and also from a cluster of seven cases of HL-AziR N gonorrhoeae reported in Hawaii in 2016. 16 A retrospective prevalence study 26 from Hangzhou, China, in 2012, found HL-AziR in 21 of 118 isolates tested, suggesting that HL-AziR might be widespread in this region. These isolates belonged to seven different NG-MAST sequence types, although some of the sequence types were more than 99% similar; 26 these were different sequence types to those found in our study.…”

Section: Discussionmentioning

confidence: 99%

Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study

Fifer

Cole

Hughes

et al. 2018

The Lancet Infectious Diseases

105

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“…Azithromycin resistance and treatment failure has subsequently been reported in a number of geographical locations. [69][70][71][72][73] In the UK, azithromycin-resistant N. gonorrhoeae has been detected intermittently since 2004, 74,75 with an ongoing outbreak of high-level azithromycin-resistant isolates identified in England since 2014. 76 The Gonococcal Resistance to Antimicrobials Surveillance Programme reported that 10% of gonococcal isolates in England and Wales had a MIC of > 0.5 mg/l in 2015, indicating probable resistance.…”

Section: The Role Of Azithromycin In the Treatment Of Gonorrhoeamentioning

confidence: 99%

Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT

Ross

Harding

Duley

et al. 2019

Health Technol Assess

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Background Gonorrhoea is a common sexually transmitted infection that can cause pain and discomfort, affect fertility in women and lead to epididymo-orchitis in men. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance reducing its effectiveness. Gentamicin is a potential alternative treatment requiring further evaluation. Objectives To assess the clinical effectiveness and cost-effectiveness of gentamicin as an alternative treatment to ceftriaxone in the treatment of gonorrhoea. Design A multicentre, parallel-group, blinded, non-inferiority randomised controlled trial. Setting Fourteen sexual health clinics in England. Participants Adults aged 16–70 years with a diagnosis of uncomplicated, untreated genital, pharyngeal or rectal gonorrhoea based on a positive Gram-stained smear on microscopy or a positive nucleic acid amplification test (NAAT). Randomisation and blinding Participants were randomised using a secure web-based system, stratified by clinic. Participants, investigators and research staff assessing participants were blinded to treatment allocation. Interventions Allocation was to either 240 mg of gentamicin (intervention) or 500 mg of ceftriaxone (standard treatment), both administered as a single intramuscular injection. All participants also received 1 g of oral azithromycin. Main outcome measure The primary outcome measure was clearance of Neisseria gonorrhoeae at all infected sites, confirmed by a negative Aptima Combo 2® (Hologic Inc., Marlborough, MA, USA) NAAT, at 2 weeks post treatment. Results We randomised 720 participants, of whom 81% were men. There were 358 participants in the gentamicin group and 362 in the ceftriaxone group; 292 (82%) and 306 (85%) participants, respectively, were included in the primary analysis. Non-inferiority of gentamicin to ceftriaxone could not be demonstrated [adjusted risk difference for microbiological clearance –6.4%, 95% confidence interval (CI) –10.4% to –2.4%]. Clearance of genital infection was similar in the two groups, at 94% in the gentamicin group and 98% in the ceftriaxone group, but clearance of pharyngeal infection and rectal infection was lower in the gentamicin group (80% vs. 96% and 90% vs. 98%, respectively). Reported pain at the injection site was higher for gentamicin than for ceftriaxone. The side-effect profiles were comparable between the groups. Only one serious adverse event was reported and this was deemed not to be related to the trial medication. The economic analysis found that treatment with gentamicin is not cost neutral compared with standard care, with average patient treatment costs higher for those allocated to gentamicin (£13.90, 95% CI £2.47 to £37.34) than to ceftriaxone (£6.72, 95% CI £1.36 to £17.84). Limitations Loss to follow-up was 17% but was similar in both treatment arms. Twelve per cent of participants had a negative NAAT for gonorrhoea at their baseline visit but this was balanced between treatment groups and unlikely to have biased the trial results. Conclusions The trial was unable to demonstrate non-inferiority of gentamicin compared with ceftriaxone in the clearance of gonorrhoea at all infected sites. Clearance at pharyngeal and rectal sites was lower for participants allocated to gentamicin than for those allocated to ceftriaxone, but was similar for genital sites in both groups. Gentamicin was associated with more severe injection site pain. However, both gentamicin and ceftriaxone appeared to be well tolerated. Future work Exploration of the genetic determinants of antibiotic resistance in N. gonorrhoeae will help to identify accurate markers of decreased susceptibility. Greater understanding of the immune response to infection can assist gonococcal vaccine development. Trial registration Current Controlled Trials ISRCTN51783227. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 20. See the NIHR Journals Library website for further project information.

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High prevalence ofNeisseria gonorrhoeaewith high-level resistance to azithromycin in Hangzhou, China: Table 1.

Cited by 30 publications

References 10 publications

Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018

Emergence and Spread of Neisseria gonorrhoeae Strains with High-Level Resistance to Azithromycin in Taiwan from 2001 to 2018

Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study

Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT

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