Search

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.

Background: Provider adherence to the national treatment guidelines for gonorrhea is critical to assuring effective treatment. It is also an important means of limiting antibiotic overuse, which can lead to development of resistant bacteria. The Chinese treatment guidelines recommend the monotherapy with ceftriaxone or spectinomycin in accordance with the World Health Organization guidelines for treatment of uncomplicated gonorrhea. We evaluated adherence to the guidelines among treatment providers in China., Methods: The study was a nationwide cross-sectional study. In each of the 6 geographic regions in China, at least 1 province was selected. In each selected province, cities with elevated incidence of reported gonorrhea were purposively selected. Using a questionnaire, 2121 physicians recruited from 512 different categories and levels of health sectors from July to September 2017 were investigated., Results: Of the participants, more than 99% diagnosed gonorrhea using one of the laboratory tests including Gram stain, culture, nucleic acid amplification test, or other tests. Culture was the predominant assay of the choice for the diagnosis. Of the 1890 physicians who provided information on prescription behaviors, 62.2% were not adherent to the regimens for treatment of uncomplicated gonorrhea recommended by the National Sexually Transmitted Disease (STD) Treatment Guidelines (National STD Guidelines). Physicians working in the areas located in Northern China (adjusted odds ratio [AOR], 3.06; 95% confidence intervals [CIs], 1.77-5.31), in general hospitals or departments of urology (AOR, 1.54; 95% CIs, 1.08-2.19), diagnosing more cases in the past 6 months (AOR, 1.82; 95% CIs, 1.25-2.67), or unfamiliar with the treatment regimens in the National STD Guidelines (AOR, 3.48; 95% CIs, 2.76-4.37) were significantly more likely to be nonadherent to the National STD Guidelines., Conclusions: It can be concluded from our study that nonadherence to the national guidelines and empirical treatment with high doses of ceftriaxone occurred frequently in China. Further studies on the impacts of the empirical treatment on antimicrobial resistance of gonorrhea are needed.

Background: Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China., Methods and Findings: In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual., Conclusions: To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.

Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. This is the first nationwide study, performed within the China Gonococcal Antimicrobial Susceptibility Programme (China-GASP), regarding AMR, including ceftriaxone genetic resistance determinants, and molecular epidemiology of gonococci in China., Methods: Gonococcal isolates (n = 1257) from consecutive patients were collected at 11 sentinel sites distributed across China during 2012-13. Susceptibility to ceftriaxone, spectinomycin, ciprofloxacin and tetracycline was determined using the agar dilution method. Ceftriaxone resistance determinants penA and penB were examined using sequencing. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology., Results: Among isolates, 0.2% were resistant to spectinomycin, 4.4% to ceftriaxone, 42.9% to tetracyclines (high-level resistance) and 99.8% to ciprofloxacin. Among 890 sequenced isolates, 16 (1.8%) possessed a penA mosaic allele; 4 of these isolates belonged to the MDR internationally spread NG-MAST genogroup G1407 (first description in China). Non-mosaic penA alleles with an A501T mutation and an A102D alteration in porB1b were statistically associated with decreased susceptibility/resistance to ceftriaxone. NG-MAST G10339, G1424 and G1053 were associated with decreased susceptibility/resistance to ceftriaxone., Conclusions: In China, ceftriaxone and spectinomycin can continue to be recommended for gonorrhoea treatment, with the possible exception of Hainan and Sichuan provinces where ceftriaxone resistance exceeded 5% and AMR surveillance needs to be strengthened. Molecular approaches including genotyping and AMR determinant analysis can be valuable to supplement and enhance conventional surveillance of gonococcal AMR in China., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major problem worldwide. This study investigated the AMR, genetic ceftriaxone resistance determinants and molecular epidemiology of N. gonorrhoeae in Nanjing, China., Methods: N. gonorrhoeae isolates were collected in 2007 (n = 198) and 2012 (n = 80). The susceptibility to ceftriaxone, spectinomycin, ciprofloxacin and tetracycline was determined using an agar-dilution method. The ceftriaxone resistance determinants penA, mtrR and penB were examined using sequencing. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed for molecular epidemiology., Results: All isolates were resistant to ciprofloxacin, 42.4% produced β-lactamase and 34.9% showed high-level resistance to tetracycline (MIC ≥16 mg/L). In total, 5.4% of isolates were resistant to ceftriaxone; however, all of these isolates were obtained in 2007 and the susceptibility to ceftriaxone appeared to have increased. All isolates were susceptible to spectinomycin. No penA mosaic alleles were found. Non-mosaic penA alleles with A501T and G542S alterations, an H105Y alteration in mtrR and an A102D/N alteration in porB1b were statistically associated with decreased susceptibility or resistance to ceftriaxone. The most prevalent NG-MAST sequence types (STs) were ST568 (n = 13), ST270 (n = 9) and ST421 (n = 7). ST270 was the most common ST in isolates with decreased susceptibility or resistance to ceftriaxone., Conclusions: Ceftriaxone, ideally 500 mg and together with azithromycin (1-2 g), should be recommended for treatment of gonorrhoea in Nanjing, China. However, N. gonorrhoeae strains with resistance to ceftriaxone have been found in Nanjing. NG-MAST and ceftriaxone resistance determinant analysis can be valuable to supplement the antimicrobial resistance surveillance in China, which needs to be further strengthened., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Neisseria gonorrhoeae, resistant to the first-line treatment option ceftriaxone, is widespread in China from 2016. Nowadays, diverse reagents of disks and strips for rapid gonococcal antimicrobial susceptibility tests used in clinics are culture-based disks diffusion and gradient strips methods. This study aimed to evaluate the accuracy, quality, and availability of almost all disks and strips acquired in the Chinese market and serve as a reference for clinical selection. Methods: We tested the performance of 15 commercial disks and 9 commercial gradient strips acquired in China, compared with traditional agar dilution method. The overall performance was evaluated by the categorical agreement. The reagent accuracy of gradient strips was assessed by the essential agreement. Results: A total of 167 gonococcal isolates were used to evaluate antimicrobial disks from three brands. The overall categorical agreements were 71.7% to 81.8% for ceftriaxone, less than 58% for cefixime, 100% for spectinomycin, over 98% for ciprofloxacin, below 70.5% for penicillin, and 73.3% to 81.8% for tetracycline. A total of 81 isolates were tested for different gradient strips. Categorical agreements were over 96% for ceftriaxone, 86.2% for azithromycin, 62.3% to 67.1% for penicillin, 41.9% to 67.5% for tetracycline, and 95% for ciprofloxacin. Essential agreements were 57.7% to 87.3% for ceftriaxone, 70% for azithromycin, 64.9% to 68.4% for penicillin, 51.8% to 71.2% for tetracycline, and 91.3% for ciprofloxacin. Conclusion: Rapid test reagents of disks and strips based on gonococcal culture have suboptimal performance. Disk diffusion for spectinomycin or ciprofloxacin can be recommended for clinical individualized prescription. The gradient strips are of great value to identify ceftriaxone-resistant gonococcal strains. Furthermore, abundant improvements are required for many reagents to further optimize their accuracy till the fulfillment of molecular detection. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018. Methods: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected. Results: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤ 0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥ 0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P < 0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = − 0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥ 0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥ 0.25 mg/L for ertapenem. Conclusion: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections. [ABSTRACT FROM AUTHOR]

Background: Ceftriaxone resistance in Neisseria gonorrhoeae has become an imminent threat to effective control of gonorrhoea globally. In recent years, the ceftriaxone-resistant FC428 clone has shown international dissemination. After our first report of the FC428 clone in China in 2016, we now describe another six cases of FC428-related ceftriaxone-resistant N. gonorrhoeae isolates from 2017 and 2018.Objectives: To identify the phenotypic and molecular characteristics of newly reported ceftriaxone-resistant isolates in China and to investigate the relationship between these isolates and FC428 clones reported globally.Methods: Antimicrobial susceptibility to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, ciprofloxacin and tetracycline was determined by the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed for genotyping and SNPs extracted from whole-genome sequences were used for phylogenetic analysis.Results: All isolates were resistant to ceftriaxone, cefixime, penicillin, tetracycline and ciprofloxacin, but were susceptible to azithromycin and spectinomycin. NG-MAST, MLST and NG-STAR genotyping showed that all isolates shared identical or similar STs (<10 bp difference) to FC428 (NG-MAST ST3435, MLST ST1903, NG-STAR ST233) and contained the same mosaic penA allele 60.001. Phylogenetic analysis showed the Chinese isolates spreading in the whole phylogenetic tree and fully mixed with other international isolates. Half of the Chinese isolates were more closely related (<100 SNPs) to Japanese isolates than other international isolates.Conclusions: The newly reported cases in China were related to the internationally spreading FC428 clone. These isolates might have played a central role in international transmission of the FC428 clone. High ceftriaxone doses (1-2 g) still provide effective therapy. [ABSTRACT FROM AUTHOR]

Purpose: Injectable ceftriaxone and oral cefixime are the last agents effective against Neisseria gonorrhoeae. In vitro antimicrobial-susceptibility testing (AST) is done to identify the most efficacious antibiotic needed to combat the infection in that particular individual. The objective of this study was to evaluate whether Kirby–Bauer (KB) disk-diffusion tests can detect N. gonorrhoeae isolates that have decreased susceptibility to ceftriaxone and cefixime for appropriate clinical management. Methods: A total of 1,633 consecutive clinical isolates of N. gonorrhoeae were collected from January 1, 2013 to December 31, 2017 from seven dermatology clinics located in five provinces in China. Consistency between KB disk-diffusion tests and the agar-dilution method, as well as sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime, were determined using 1,306 clinical isolates that had been recovered to complete agar-dilution AST. Results: The prevalence of isolates with decreased susceptibility to ceftriaxone and cefixime was 12.1% (198 of 1,633) and 12.7% (208 of 1,633), respectively, using KB disk-diffusion tests. The prevalence of isolates with decreased susceptibility was 9.9% (129 of 1,306) for ceftriaxone and 9.9% (129 of 1,305) for cefixime using agar-dilution AST. The categorical agreement of these two methods was 80.9% for both ceftriaxone and cefixime. Compared to agar-dilution AST, the sensitivity of the KB test for detecting N. gonorrhoeae isolates with decreased susceptibility was 22.5% (29 of 129) for ceftriaxone and 29.5% (38 of 129) for cefixime, and its specificity 87.3% (1,028 of 1,177) for ceftriaxone and 86.7% (1,018 of 1,176) for cefixime. Conclusion: Although KB tests are easy to carry out in clinical practice, their ability to detect cephalosporin-resistant gonorrhoea strains is limited. This method is not an appropriate selection for screening cephalosporin-resistant gonorrhoea strains in clinical practice in China. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. Materials and Methods: A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. Results: The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. Conclusion: We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use. [ABSTRACT FROM AUTHOR]

Purpose: Gentamicin is a promising antimicrobial for the treatment of gonorrhea. The study aimed to evaluate gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates in China. Methods: In this study, the agar dilution method was used to determine the MICs of 470 isolates collected in 2016 to four effective antimicrobials (gentamicin, azithromycin, ceftriaxone, and spectinomycin). Results: Gentamicin MICs ranged from 1 to 8 mg/L. No isolate was resistant to gentamicin. Of seven isolates simultaneously resistant to azithromycin and ceftriaxone, 6 isolates demonstrated MICs of 4 mg/L or less to gentamicin. No cross relationships were found between MICs of gentamicinand susceptibility profiles of azithromycin, ceftriaxone, and spectinomycin. Conclusion: The in vitro results suggest that gentamicin can be a promising treatment option for gonococcal infections in China. Clinical trials to evaluate the therapeutic efficacy of gentamicin are required. [ABSTRACT FROM AUTHOR]

Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. This is the first nationwide study, performed within the China Gonococcal Antimicrobial Susceptibility Programme (China-GASP), regarding AMR, including ceftriaxone genetic resistance determinants, and molecular epidemiology of gonococci in China.Methods: Gonococcal isolates (n = 1257) from consecutive patients were collected at 11 sentinel sites distributed across China during 2012-13. Susceptibility to ceftriaxone, spectinomycin, ciprofloxacin and tetracycline was determined using the agar dilution method. Ceftriaxone resistance determinants penA and penB were examined using sequencing. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology.Results: Among isolates, 0.2% were resistant to spectinomycin, 4.4% to ceftriaxone, 42.9% to tetracyclines (high-level resistance) and 99.8% to ciprofloxacin. Among 890 sequenced isolates, 16 (1.8%) possessed a penA mosaic allele; 4 of these isolates belonged to the MDR internationally spread NG-MAST genogroup G1407 (first description in China). Non-mosaic penA alleles with an A501T mutation and an A102D alteration in porB1b were statistically associated with decreased susceptibility/resistance to ceftriaxone. NG-MAST G10339, G1424 and G1053 were associated with decreased susceptibility/resistance to ceftriaxone.Conclusions: In China, ceftriaxone and spectinomycin can continue to be recommended for gonorrhoea treatment, with the possible exception of Hainan and Sichuan provinces where ceftriaxone resistance exceeded 5% and AMR surveillance needs to be strengthened. Molecular approaches including genotyping and AMR determinant analysis can be valuable to supplement and enhance conventional surveillance of gonococcal AMR in China. [ABSTRACT FROM AUTHOR]