| 1. |
- Pitt, Rachel, et al.
(författare)
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Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population
- 2020
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 96:6, s. 464-468
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mycoplasma genitaliumis a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations inM. genitaliumamong the sexually-active British general population.Methods: The third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16-74 years in Britain conducted during 2010-12. Urine test results forM. genitaliumwere available for 4507 participants aged 16-44 years reporting>1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA andparCgenes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively.Results: 94% (66/70) of specimens were re-confirmed asM. genitaliumpositive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) forparCgenes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and inparC(encodingParCD87N/D87Y) in 3.3% (0.9%-11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%-73.3%) vs 10.6% (4.6%-22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%-66.8%) vs 5.0% (1.4%-16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms.Conclusions: This study highlights challenges inM. genitaliummanagement and control. Macrolide resistance was present in one in six specimens from the general population in 2010-2012, but no participants with AMRM. genitaliumreported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended.
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| 2. |
- Cole, Michelle J., et al.
(författare)
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Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data
- 2019
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.RESULTS: dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.
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| 3. |
- Ison, Catherine A., et al.
(författare)
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Current and future treatment options for gonorrhoea
- 2013
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Ingår i: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 89:4, s. 52-56
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Tidskriftsartikel (refereegranskat)abstract
- The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give > 95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.
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| 4. |
- Ison, Catherine A., et al.
(författare)
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Evolution of Neisseria gonorrhoeae is a continuing challenge for molecular detection of gonorrhoea : false negative gonococcal porA mutants are spreading internationally
- 2013
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 89:3, s. 197-201
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Identification of genetic targets specific to Neisseria gonorrhoeae for use in molecular detection methods has been a challenge. The porA pseudogene in N gonorrhoeae has been commonly used but recently gonococcal isolates giving a negative result in these PCRs have been reported. Here we describe the characterisation of two such gonococcal isolates received by the reference service at the Health Protection Agency, London, England.Methods: Phenotypic characterisation was achieved using conventional biochemical and immunological tests, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), antimicrobial susceptibility testing, serovar determination and detection of meningococcal PorA using monoclonal antibody 4BG4-E7. Genetic species confirmation was determined using commercial and in house PCRs and 16S rRNA gene sequencing. Molecular typing using the N gonorrhoeae multi-antigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) was performed. The DNA sequence of the full-length gonococcal porA pseudogene was determined and compared with published sequences.Results: Both isolates were confirmed, biochemically and immunologically as N gonorrhoeae, but repeatedly gave negative results with two in house real-time PCR assays for the porA pseudogene. Further characterisation of these isolates identified the presence of a meningococcal porA sequence and showed these isolates belong to serovar Bropyst, and to NG-MAST sequence type (ST) 5967 and MLST ST1901.Conclusions: Gonococcal isolates that give false negative results with porA pseudogene PCR assays have now been identified in four countries, three of which are in Europe, and do not appear clonal. This report highlights the genetic diversity of N gonorrhoeae, which remains a challenge for the molecular detection methods.
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| 5. |
- Seth-Smith, Helena M. B., et al.
(författare)
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Whole-genome sequences of Chlamydia trachomatis directly from clinical samples without culture
- 2013
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press (CSHL). - 1088-9051 .- 1549-5469. ; 23:5, s. 855-866
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Tidskriftsartikel (refereegranskat)abstract
- The use of whole-genome sequencing as a tool for the study of infectious bacteria is of growing clinical interest. Chlamydia trachomatis is responsible for sexually transmitted infections and the blinding disease trachoma, which affect hundreds of millions of people worldwide. Recombination is widespread within the genome of C. trachomatis, thus whole-genome sequencing is necessary to understand the evolution, diversity, and epidemiology of this pathogen. Culture of C trachomatis has, until now, been a prerequisite to obtain DNA for whole-genome sequencing; however, as C trachomatis is an obligate intracellular pathogen, this procedure is technically demanding and time consuming. Discarded clinical samples represent a large resource for sequencing the genomes of pathogens, yet clinical swabs frequently contain very low levels of C trachomatis DNA and large amounts of contaminating microbial and human DNA. To determine whether it is possible to obtain whole-genome sequences from bacteria without the need for culture, we have devised an approach that combines immunomagnetic separation (IMS) for targeted bacterial enrichment with multiple displacement amplification (MDA) for whole-genome amplification. Using IMS-MDA ill conjunction with high-throughput multiplexed Illumina sequencing, we have produced the first whole bacterial genome sequences direct from clinical samples. We also show that this method can be used to generate genome data from nonviable archived samples. This method will prove a useful tool in answering questions relating to the biology of many difficult-to-culture or fastidious bacteria of clinical concern.
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| 6. |
- Spiteri, Gianfranco, et al.
(författare)
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The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP)-a sentinel approach in the European Union (EU)/European Economic Area (EEA)
- 2013
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 89:4, s. 16-18
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance in Neisseria gonorrhoeae is monitored in the European Union/European Economic Area through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) coordinated by the European Centre for Disease Prevention and Control. Euro-GASP includes a sentinel surveillance programme which aims to detect in a timely manner changes in resistance patterns and inform treatment guidelines. The programme aims to test a representative number of isolates from each European Union/European Economic Area member state per year for a range of therapeutically relevant antimicrobials through a biannual hybrid centralised/decentralised system. Testing is supported by an External Quality Assurance programme and a laboratory training programme. Participation in the programme has increased to 21 countries in 2012. Euro-GASP has been able to detect the rapid spread of isolates with decreased susceptibility to cefixime across Europe in 2010 and 2011. Results from the programme have informed changes in European treatment guidelines for gonorrhoea and led to the development of the 'Response plan to control and manage the threat of multidrug resistant gonorrhoea in Europe'. Future challenges for Euro-GASP include supporting countries to participate in Euro-GASP through decentralised testing, improving timeliness and epidemiological data quality, and increasing participation from Eastern Europe.
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| 7. |
- Unemo, Magnus, et al.
(författare)
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Gonorrhoea and gonococcal antimicrobial resistance surveillance networks in the WHO European Region, including the independent countries of the former Soviet Union
- 2013
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 89:4, s. 42-46
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) in Neisseria gonorrhoeae has emerged for essentially all antimicrobials following their introduction into clinical practice. During the latest decade, susceptibility to the last remaining options for antimicrobial monotherapy, the extended-spectrum cephalosporins (ESC), has markedly decreased internationally and treatment failures with these ESCs have been verified. In response to this developing situation, WHO and the European Centre for Disease Prevention and Control (ECDC) have published global and region-specific response plans, respectively. One main component of these action/response plans is to enhance the surveillance of AMR and treatment failures. This paper describes the perspectives from the diverse WHO European Region (53 countries), including the independent countries of the former Soviet Union, regarding gonococcal AMR surveillance networks. The WHO European Region has a high prevalence of resistance to all previously recommended antimicrobials, and most of the first strictly verified treatment failures with cefixime and ceftriaxone were also reported from Europe. In the European Union/European Economic Area (EU/EEA), the European gonococcal antimicrobial surveillance programme (Euro-GASP) funded by the ECDC is running. In 2011, the Euro-GASP included 21/31 (68%) EU/EEA countries, and the programme is further strengthened annually. However, in the non-EU/EEA countries, internationally reported and quality assured gonococcal AMR data are lacking in 87% of the countries and, worryingly, appropriate support for establishment of a GASP is still lacking. Accordingly, national and international support, including political and financial commitment, for gonococcal AMR surveillance in the non-EU/EEA countries of the WHO European Region is essential.
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