Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia.
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SUBMITTER: Whiley DM
PROVIDER: S-EPMC5572890 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization's Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends.ObjectiveThis study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda.MethodsMen attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization's EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods-disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing.ResultsOf 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity.ConclusionsThis is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.
| S-EPMC7315362 | biostudies-literature
Project description:The emergence of Neisseria gonorrhoeae strains that are resistant to azithromycin and extended-spectrum cephalosporins represents a public health threat, that of untreatable gonorrhea infections. Multivariate regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to the overall antimicrobial MICs for ceftriaxone, cefixime, azithromycin, tetracycline, ciprofloxacin, and penicillin. A training data set consisting of 1,280 N. gonorrhoeae strains was used to generate regression equations which were then applied to validation data sets of Canadian (n?=?1,095) and international (n?=?431) strains. The predicted MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) were fully explained by 5 amino acid substitutions in PenA, A311V, A501P/T/V, N513Y, A517G, and G543S; the presence of a disrupted mtrR promoter; and the PorB G120 and PonA L421P mutations. The correlation of predicted MICs within one doubling dilution to phenotypically determined MICs of the Canadian validation data set was 95.0% for ceftriaxone, 95.6% for cefixime, 91.4% for azithromycin, 98.2% for tetracycline, 90.4% for ciprofloxacin, and 92.3% for penicillin, with an overall sensitivity of 99.9% and specificity of 97.1%. The correlations of predicted MIC values to the phenotypically determined MICs were similar to those from phenotype MIC-only comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics to better monitor the dynamics of N. gonorrhoeae.
| S-EPMC7038236 | biostudies-literature
Project description:In a Policy Forum, Teodora Wi and colleagues discuss the challenges of antimicrobial resistance in gonococci.
| S-EPMC5501266 | biostudies-literature
Project description:Surveillance of gonococcal antimicrobial resistance and the molecular characterization of the mechanisms underlying these resistance phenotypes are essential in order to establish correct empirical therapies, as well as to describe the emergence of new mechanisms in local bacterial populations. To address these goals, 149 isolates were collected over a 1-month period (October-November 2008) at the Ontario Public Health Laboratory, Toronto, Canada, and susceptibility profiles (8 antibiotics) were examined. Mutations in previously identified targets or the presence of some enzymes related to resistance (r), nonsusceptibility (ns) (resistant plus intermediate categories), or reduced susceptibility (rs) to the antibiotics tested were also studied. A significant proportion of nonsusceptibility to penicillin (PEN) (89.2%), tetracycline (TET) (72.3%), ciprofloxacin (CIP) (29%), and macrolides (erythromycin [ERY] and azithromycin; 22.3%) was found in these strains. Multidrug resistance was observed in 18.8% of the collection. Although all the strains were susceptible to spectinomycin and extended-spectrum cephalosporins (ESC) (ceftriaxone and cefixime), 9.4% of them displayed reduced susceptibility to extended-spectrum cephalosporins. PBP 2 mosaic structures were found in all of these ESC(rs) isolates. Alterations in the mtrR promoter, MtrR repressor (TET(r), PEN(ns), ESC(rs), and ERY(ns)), porin PIB (TET(r) and PEN(ns)), and ribosomal protein S10 (TET(r)) and double mutations in gyrA and parC quinolone resistance-determining regions (QRDRs) (CIP(r)) were associated with and presumably responsible for the resistance phenotypes observed. This is the first description of ESC(rs) in Canada. The detection of this phenotype indicates a change in the epidemiology of this resistance and highlights the importance of continued surveillance to preserve the last antimicrobial options available.
| S-EPMC3028768 | biostudies-literature
Project description:Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international populations. This is crucial for developing or refining treatment guidelines. N. gonorrhoeae multiantigen sequence typing (NG-MAST) is beneficial for describing the molecular epidemiology of gonococci at national and international levels. Elucidation of AMR determinants to ?-lactam drugs, is a means of monitoring the development of resistance. In Ghana, little is known about the current gonococcal AMR prevalence and no characterization of gonococcal isolates has been previously performed. In this study, gonococcal isolates (n = 44) collected from five health facilities in Ghana from 2012 to 2015, were examined using AMR testing, NG-MAST and sequencing of penA. High rates of resistance were identified to tetracycline (100%), benzylpenicillin (90.9%), and ciprofloxacin (81.8%). One isolate had a high cefixime MIC (0.75 ?g/ml). Twenty-eight NG-MAST sequence types (STs) were identified, seventeen of which were novel. The isolate with the high cefixime MIC contained a mosaic penA-34 allele and belonged to NG-MAST ST1407, an internationally spreading multidrug-resistant clone that has accounted for most cefixime resistance in many countries. In conclusion, AMR testing, NG-MAST, and sequencing of the AMR determinant penA, revealed high rates of resistance to tetracycline, benzylpenicillin, and ciprofloxacin; as well as a highly diverse population of N. gonorrhoeae in Ghana. It is imperative to continue with enhanced AMR surveillance and to understand the molecular epidemiology of gonococcal strains circulating in Ghana and other African countries.
| S-EPMC6786528 | biostudies-literature
Project description:BackgroundGonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to a lack of resolution in strain typing methods.MethodsIn this study, we assess how the core genome can be used to improve our understanding of gonococcal population structure compared with current typing schemes.ResultsA total of 1668 loci were identified as core to the gonococcal genome. These were organized into a core genome multilocus sequence typing scheme (N gonorrhoeae cgMLST v1.0). A clustering algorithm using a threshold of 400 allelic differences between isolates resolved gonococci into discrete and stable core genome groups, some of which persisted for multiple decades. These groups were associated with antimicrobial genotypes and non-overlapping NG-STAR and NG-MAST sequence types. The MLST-STs were more widely distributed among core genome groups.ConclusionsClustering with cgMLST identified globally distributed, persistent, gonococcal lineages improving understanding of the population biology of gonococci and revealing its population structure. These findings have implications for the emergence of antimicrobial resistance in gonococci and how this is associated with lineages, some of which are more predisposed to developing antimicrobial resistance than others.
| S-EPMC7653085 | biostudies-literature
Project description:The choice of adequate methods for epidemiological purposes remains a challenging problem in Neisseria gonorrhoeae molecular monitoring. In this study, the collection of geographically unrelated gonococci (n = 103) isolated in Russian clinics was comparably tested by (i) a traditional serotyping scheme, (ii) por typing, (iii) Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST), and (iv) multilocus sequence typing (MLST). It is shown that, according to sequencing data, a third of the strains carried new porB1 alleles, as well as tbpB ones, and more than half of the samples had new sequence types (STs) as determined by NG-MAST or MLST. The discriminatory power for each typing method was calculated by using the Hunter-Gaston discriminatory index, D. Commonly, modern nucleic acid-based typing methods (por typing, NG-MAST, and MLST) appeared to be more efficient than the classical serotyping scheme. While the traditional serotyping gave a D value of 0.82, the por typing, NG-MAST, and MLST approaches yielded D values of 0.97, 0.98, and 0.91, respectively. Each typing technique revealed the distribution of gonococci slightly correlated with their geographical sources. However, only the MLST method STs were highly associated with certain phenotypes. Although ST1594, ST1892, and ST6720 were typical for susceptible gonococci, ST1901 and ST6716 were undoubtedly associated with a multidrug-resistant phenotype. We conclude that every tested nucleic acid-based typing method is suitable for N. gonorrhoeae molecular surveillance. However, the MLST method seems to serve large-scale epidemiological purposes, whereas the NG-MAST and por typing approaches are more appropriate for the investigation of local outbreaks.
| S-EPMC2953076 | biostudies-literature
Project description:The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85?% of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99?% sensitivity and 100?% specificity. Approximately 10?% showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide.
| S-EPMC6159555 | biostudies-literature
Project description:OBJECTIVES:Neisseria gonorrhoeae (NG) is a significant global public health concern due to rising diagnoses rates and antimicrobial resistance. Molecular combined with epidemiological data have been used to understand the distribution and spread of NG, as well as relationships between cases in sexual networks, but the public health value gained from these studies is unclear. We conducted a systematic review to examine how molecular epidemiological studies have informed understanding of sexual networks and NG transmission, and subsequent public health interventions. METHODS:Five research databases were systematically searched up to 31st March 2017 for studies that used sequence-based DNA typing methods, including whole genome sequencing, and linked molecular data to patient-level epidemiological data. Data were extracted and summarised to identify common themes. RESULTS:Of the 49 studies included, 82% used NG Multi-antigen Sequence Typing. Gender and sexual orientation were commonly used to characterise sexual networks that were inferred using molecular clusters; clusters predominantly of one patient group often contained a small number of isolates from other patient groups. Suggested public health applications included using these data to target interventions at specific populations, confirm outbreaks, and inform partner management, but these were mainly untested. CONCLUSIONS:Combining molecular and epidemiological data has provided insight into sexual mixing patterns, and dissemination of NG, but few studies have applied these findings to design or evaluate public health interventions. Future studies should focus on the application of molecular epidemiology in public health practice to provide evidence for how to prevent and control NG.
| S-EPMC5999358 | biostudies-literature
Project description:A multitarget PCR was developed for the direct detection of penicillinase-producing Neisseria gonorrhoeae (PPNG). The assay was validated by testing 342 PPNG isolates and 415 clinical samples. The method is suitable for routine detection of PPNG strains. Its multitarget approach reduces the potential for false-negative results caused by sequence variations.
| S-EPMC4508450 | biostudies-literature