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Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

ABSTRACT: The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs.

SUBMITTER: Cristillo AD

PROVIDER: S-EPMC6370498 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

Cristillo Anthony D AD Bristow Claire C CC Torrone Elizabeth E Dillon Jo-Anne JA Kirkcaldy Robert D RD Dong Huan H Grad Yonatan H YH Nicholas Robert A RA Rice Peter A PA Lawrence Kenneth K Oldach David D Shafer William Maurice WM Zhou Pei P Wi Teodora E TE Morris Sheldon R SR Klausner Jeffrey D JD

Sexually transmitted diseases 20190301 3

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG gl ...[more]

PMID: 30363025

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Project description:BackgroundAntimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia.MethodsA cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset.ResultsThe most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates.ConclusionThis study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.

Project description:BackgroundNeisseria gonorrhoeae, the causative agent for sexually transmitted infection (STI) gonorrhoea, has emerged with a significant public health impact on acquiring resistance to antimicrobials available for treatment. The resistance of N. gonorrhoeae limit treatment options and contributed to high morbidity associated with gonorrhoea. Data on antimicrobial resistance (AMR) profiles in N. gonorrhoeae is scares in Zambia. This study aimed to determine the antibiotic susceptibilities in N. gonorrhoeae isolates from Lusaka, Zambia.MethodsA prospective cross-sectional study was conducted on 630 STI patients who presented with urethral or vaginal discharge from 2019 to 2020. Urethral and endocervical secretions were cultured on Modified Thayer Martin agar and incubated at 36 °C ± 1 °C in 5% CO2 for 24 h. Identification of N. gonorrhoeae isolates was achieved by Gram stain, oxidase, nitrocefin disk, BactiCard Neisseria, and Viteck® Compact. The AMR profiles were determined using E-test. Statistical significant was determined by Pearson's Chi-square test, Mann-Whitney U test, or logistic regression with p-values of < 0.05 indicating significance.ResultsA total of 630 patients were recruited of which 46% (290/630) with the median of 29 years and interquartile range (IQR) of 19-39 years were male. The median of the females was 26 years and IQR of 15-37 years. Neisseria gonorrhoeae was isolated from 19.4% (122/630) patients of which 72.9% (89/122) were male, with highest prevalence of isolation in the age category of 25-34 years. The prevalence of resistance was high to penicillin (85.2%), tetracycline (68.9%) and ciprofloxacin (59.8%) with MIC90 of 32 µg/mL, 8 µg/mL, and 8 µg/mL respectively. The isolates had reduced susceptibility to cefixime (1.6%), spectinomycin (4.9%) and (4.9%) for azithromycin. All isolates were susceptible to ceftriaxone. Risk factors associated with AMR were douching in females (AOR 6.69, 95% CI; 1.11-40.31, p = 0.039), female gender (AOR 7.64, 95% CI; 1.11-52.33, p = 0.048), HIV-positivity (AOR 26.59, 95% CI; 3.67-192.7, p = 0.005), no condom use or unprotected sex (AOR 5.48, 95% CI; 1.17-22.75 p = 0.026), sex trading (AOR 4.19, 95% CI; 1.55-11.33, p = 0.010), and over-counter treatment of ciprofloxacin (AOR 3.44, 95% CI; 1.17-22.75, p = 0.023).ConclusionThe N. gonorrhoeae resistance to penicillin, tetracycline and ciprofloxacin was high necessitating revision of the treatment guidelines. However, no resistance to ceftriaxone was detected. Therefore, monitoring of antibiotic resistance remains critical in Zambia.

Project description:BackgroundEvolving gonococcal antimicrobial resistance (AMR) poses a serious threat to public health. The aim of this study was to: update antimicrobial susceptibility data of Neisseria gonorrhoeae recently isolated in Nanjing, China and identify specific deteminants of antimicrobial resistance and gentoypes of isolates with decreased sensitivity to ceftriaxone.Methods334 N. gonorrhoeae isolates were collected consecutively from symptomatic men attending the Nanjing STD Clinic between April 2011 and December 2012. The minimum inhibitory concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone were determined by agar plate dilution for each isolate. Penicillinase-producing N. gonorrhoeae (PPNG) and tetracycline-resistant N. gonorrhoeae (TRNG) were examined and typed for β-lactamase and tetM encoding plasmids respectively. Isolates that displayed elevated MICs to ceftriaxone (MIC ≥0.125 mg/L) were also tested for mutations in penA, mtrR, porB1b, ponA and pilQ genes and characterized by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST).Results98.8% (330/334) of N. gonorrhoeae isolates were resistant to ciprofloxacin; 97.9% (327/334) to tetracycline and 67.7% (226/334) to penicillin. All isolates were susceptible to ceftriaxone (MIC ≤0.25 mg/L) and spectinomycin (MIC ≤32 mg/L). Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid. Elevated MICs for ceftriaxone were present in 15 (4.5%) isolates; multiple mutations were found in penA, mtrR, porB1b and ponA genes. The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type.ConclusionsN. gonorrhoeae isolates in Nanjing generally retained similar antimicrobial resistance patterns to isolates obtained five years ago. Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent. Ceftriaxone and spectinomycin remain treatments of choice of gonorrhea in Nanjing, however, decreased susceptibility to ceftriaxone and rising MICs for spectinomycin of N. gonorrhoeae isolates underscore the importance of maintaining surveillance for AMR (both phenotypic and genotypic).

Dataset Information

Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

Publications

Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

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