High tetracycline resistance percentages in Neisseria gonorrhoeae in Europe: is doxycycline post-exposure prophylaxis unlikely to reduce the incident gonorrhoea cases?
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ABSTRACT:
SUBMITTER: Unemo M
PROVIDER: S-EPMC10928266 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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High tetracycline resistance percentages in <i>Neisseria gonorrhoeae</i> in Europe: is doxycycline post-exposure prophylaxis unlikely to reduce the incident gonorrhoea cases?
Unemo Magnus M Cole Michelle J MJ Kodmon Csaba C Day Michaela M Jacobsson Susanne S
The Lancet regional health. Europe 20240213
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Project description:Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits doxyPEP effectiveness against gonorrhea, and selection for tetracycline resistant lineages may influence prevalence of resistance to other antimicrobials via selection for multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from 5,644 clinical isolates of N. gonorrhoeae , we assessed the near-term impact of doxyPEP on N. gonorrhoeae antimicrobial resistance. We found that the impact on antimicrobial resistance is likely to be influenced by the strength of selection for plasmid-encoded and chromosomally-encoded tetracycline resistance, as isolates with high-level, plasmid-encoded resistance had lower minimum inhibitory concentrations to other antimicrobials compared to isolates with low-level tetracycline resistance. The impact of doxyPEP may differ across demographic groups and geographic regions within the United States due to variation in pre-existing tetracycline resistance.
| S-EPMC10055447 | biostudies-literature
Project description:BACKGROUND:Treatment of gonorrhea is complicated by the development of antimicrobial resistance in Neisseria gonorrhoeae (GC) to the antibiotics recommended for treatment. Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance in N. gonorrhoeae isolates recovered from Kenya between 2013 and 2018. METHODS:DNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembled de-novo using CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor. RESULTS:Twenty-four (66.7%) isolates had both ?-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaic penA alleles. All the isolates expressing TetM were tetracycline resistant (MIC>?1?mg/L) and had increased doxycycline MICs (up to 96?mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs. CONCLUSION:High-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borne blaTEM and tetM genes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.
| S-EPMC7517623 | biostudies-literature
Project description: Not available
| S-EPMC11283341 | biostudies-literature
Project description:We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST1903, NG-MAST ST3435, NG-STAR233, and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark.
| S-EPMC6152217 | biostudies-literature
Project description:ObjectivesTo (i) describe the nationwide antimicrobial susceptibility of Neisseria gonorrhoeae (NG) isolates cultured across Brazil in 2018-20 and compare it with NG antimicrobial resistance data from 2015-16, and (ii) present epidemiological data of the corresponding gonorrhoea patients in 2018-20.MethodsTwelve representative sentinel sites cultured NG isolates from men with urethral discharge. Susceptibility to eight antimicrobials was examined using agar dilution method, according to WHO standards. The consenting participants were invited to provide epidemiological data.ResultsIn total, 633 NG isolates (one isolate per participant) were analysed, and 449 (70.9%) questionnaires were answered. Heterosexual (68.2%) and homosexual (23.1%) sexual orientations were common, and most prevalent types of unprotected sexual intercourse were vaginal insertive (69.9%), oral giving (56.6%) and anal insertive (47.4%). The levels of in vitro NG resistance to ciprofloxacin, tetracycline, benzylpenicillin, azithromycin, cefixime, gentamicin, spectinomycin and ceftriaxone were 67.3%, 40.0%, 25.7%, 10.6%, 0.3%, 0%, 0% and 0%, respectively. Compliance with the recommended first-line ceftriaxone 500 mg plus azithromycin 1 g therapy was high (90.9%).ConclusionsCompared with 2015-16, ciprofloxacin resistance has remained high and azithromycin and cefixime resistance rates have increased in Brazil. Resistance remained lacking to ceftriaxone, gentamicin and spectinomycin, which all are gonorrhoea treatment options. The increasing azithromycin resistance in Brazil and internationally may threaten the future use of azithromycin in dual regimens for treatment of gonorrhoea. Consequently, continued and enhanced quality-assured surveillance of gonococcal AMR, and ideally also treatment failures and including WGS, is imperative in Brazil and worldwide.
| S-EPMC9252985 | biostudies-literature
Project description:The overall goals and objectives of this study are to investigate the transcriptomics of Neisseria gonorrhoeae using RNA-seq. This work will look at gene expression, start points of transcription, transcriptional termination, and differences between these in different conditions and between strains and growing cultures over time.
2016-05-24 | GSE73032 | GEO
Project description:BackgroundNeisseria gonorrhoeae poses an urgent public health threat because of increasing antimicrobial resistance; however, much of the circulating population remains susceptible to historical treatment regimens. Point-of-care diagnostics that report susceptibility could allow for reintroduction of these regimens, but development of such diagnostics has been restricted to ciprofloxacin, for which susceptibility can be predicted from a single locus. We aimed to define genetic variants associated with susceptibility to penicillin and tetracycline.MethodsWe collected publicly available global whole-genome sequencing data (n=12 045) from clinical N gonorrhoeae isolates, with phenotypic resistance data for penicillin (n=6935), and tetracycline (n=5727). Using conditional genome-wide association studies, we defined genetic variants associated with susceptibility to penicillin and tetracycline. We excluded isolates that could not be classified as either susceptible or resistant. To validate our results, we assembled 1479 genomes from the US Centers for Disease Control and Prevention (CDC)'s Gonococcal Isolate Surveillance Project, for which urethral specimens are collected at sentinel surveillance sites across the USA. We evaluated the sensitivity and specificity of susceptibility-associated alleles using Clinical & Laboratory Standards Institute breakpoints for susceptibility and non-resistance in both the global and validation datasets.FindingsIn our conditional penicillin genome-wide association study, the presence of a genetic variant defined by a non-mosaic penA allele without an insertion at codon 345 was associated with penicillin susceptibility and had the highest negative effect size (β) of significant variants (p=5·0x10-14, β -2·5). In combination with the absence of blaTEM, this variant predicted penicillin susceptibility with high specificity (99·8%) and modest sensitivity (36·7%). For tetracycline, the wildtype allele at rpsJ codon 57, encoding valine, was associated with tetracycline susceptibility (p=5·6x10-16, β -1·6) after conditioning on the presence of tetM. The combination of rpsJ codon 57 allele and tetM absence predicted tetracycline susceptibility with high specificity (97·2%) and sensitivity (88·7%).InterpretationAs few as two genetic loci can predict susceptibility to penicillin and tetracycline in N gonorrhoeae with high specificity. Molecular point-of-care diagnostics targeting these loci have the potential to increase available treatments for gonorrhoea.FundingNational Institute of Allergy and Infectious Diseases, the National Science Foundation, and the Smith Family Foundation.
| S-EPMC9095990 | biostudies-literature
Project description:We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.
| S-EPMC6152157 | biostudies-literature
Project description:IntroductionAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern and enhanced global gonococcal AMR surveillance is imperative. As in many African countries, regular, representative and quality-assured gonococcal AMR is lacking in Ethiopia. We describe the AMR in gonococcal isolates from five cities across Ethiopia, 2021-22, and patient epidemiological data.MethodsUrethral discharge from males and cervical discharge from females were collected from October 2021 to September 2022. Epidemiological data were collected using a questionnaire. MIC determination (ETEST; eight antimicrobials) was performed on gonococcal isolates and EUCAST breakpoints (v13.1) were used.ResultsFrom 1142 urogenital swab samples, 299 species-identified gonococcal isolates were identified; 78.3% were from males and 21.7% from females. The median age for males and females was 25 and 23 years, respectively. Most isolates (61.2%) were identified in Addis Ababa, followed by Gondar (11.4%), Adama (10.4%), Bahir Dar (10.0%) and Jimma (7.0%). The resistance level to ciprofloxacin, tetracycline and benzylpenicillin was 97.0%, 97.0% and 87.6%, respectively, and 87.6% of isolates were producing β-lactamase. All isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. Recommended therapy [ceftriaxone (250 mg) plus azithromycin (1 g)] was used for 84.2% of patients.ConclusionsWe present the first national quality-assured gonococcal AMR data from Ethiopia. Resistance levels to ciprofloxacin, tetracycline and benzylpenicillin were exceedingly high. However, all isolates were susceptible to ceftriaxone, cefixime, azithromycin and spectinomycin. In Ethiopia, it is essential to strengthen the gonococcal AMR surveillance by including further epidemiological data, more isolates from different cities, and WGS.
| S-EPMC10833647 | biostudies-literature
Project description:Whole genome sequencing (WGS) has been used to investigate transmission of Neisseria gonorrhoeae, but to date, most studies have not combined genomic data with detailed information on sexual behaviour to define the extent of transmission across population risk groups (bridging). Here, through combined epidemiological and genomic analysis of 2,186N. gonorrhoeae isolates from Australia, we show widespread transmission of N. gonorrhoeae within and between population groups. We describe distinct transmission clusters associated with men who have sex with men (MSM) and heterosexuals, and men who have sex with men and women (MSMW) are identified as a possible bridging population between these groups. Further, the study identifies transmission of N. gonorrhoeae between HIV-positive and HIV-negative individuals receiving pre-exposure prophylaxis (PrEP). Our data highlight several groups that can be targeted for interventions aimed at improving gonorrhoea control, including returning travellers, sex workers, and PrEP users.
| S-EPMC6728426 | biostudies-literature