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Antibiotic and antimicrobial resistance
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Building the European Antimicrobial Resistance Surveillance network in veterinary medicine (EARS-Vet)
Rodolphe Mader , Peter Damborg , Jean-Philippe Amat , Björn Bengtsson , Clémence Bourély , Els M Broens , Luca Busani , Paloma Crespo-Robledo , Maria-Eleni Filippitzi , William Fitzgerald , Heike Kaspar , Cristina Muñoz Madero , Madelaine Norström , Suvi Nykäsenoja , Karl Pedersen , Lucie Pokludova , Anne Margrete Urdahl , Alkiviadis Vatopoulos , Christos Zafeiridis , Jean-Yves Madec and on behalf of EU-JAMRAIAntimicrobial resistance (AMR) should be tackled through a One Health approach, as stated in the World Health Organization Global Action Plan on AMR. We describe the landscape of AMR surveillance in the European Union/European Economic Area (EU/EEA) and underline a gap regarding veterinary medicine. Current AMR surveillance efforts are of limited help to veterinary practitioners and policymakers seeking to improve antimicrobial stewardship in animal health. We propose to establish the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) to report on the AMR situation, follow AMR trends and detect emerging AMR in selected bacterial pathogens of animals. This information could be useful to advise policymakers, explore efficacy of interventions, support antimicrobial stewardship initiatives, (re-)evaluate marketing authorisations of antimicrobials, generate epidemiological cut-off values, assess risk of zoonotic AMR transmission and evaluate the burden of AMR in animal health. EARS-Vet could be integrated with other AMR monitoring systems in the animal and medical sectors to ensure a One Health approach. Herein, we present a strategy to establish EARS-Vet as a network of national surveillance systems and highlight challenges of data harmonisation and bias. Strong political commitment at national and EU/EEA levels is required for the success of EARS-Vet.
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Prospective genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) associated with bloodstream infection, England, 1 October 2012 to 30 September 2013
BackgroundMandatory reporting of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) has occurred in England for over 15years. Epidemiological information is recorded, but routine collection of isolates for characterisation has not been routinely undertaken. Ongoing developments in whole-genome sequencing (WGS) have demonstrated its value in outbreak investigations and for determining the spread of antimicrobial resistance and bacterial population structure. Benefits of adding genomics to routine epidemiological MRSA surveillance are unknown.
AimTo determine feasibility and potential utility of adding genomics to epidemiological surveillance of MRSA.
MethodsWe conducted an epidemiological and genomic survey of MRSA BSI in England over a 1-year period (1 October 2012–30 September 2013).
ResultsDuring the study period, 903 cases of MRSA BSI were reported; 425 isolates were available for sequencing of which, 276 (65%) were clonal complex (CC) 22. Addition of 64 MRSA genomes from published outbreak investigations showed that the study genomes could provide context for outbreak isolates and supported cluster identification. Comparison to other MRSA genome collections demonstrated variation in clonal diversity achieved through different sampling strategies and identified potentially high-risk clones e.g. USA300 and local expansion of CC5 MRSA in South West England.
ConclusionsWe demonstrate the potential utility of combined epidemiological and genomic MRSA BSI surveillance to determine the national population structure of MRSA, contextualise previous MRSA outbreaks, and detect potentially high-risk lineages. These findings support the integration of epidemiological and genomic surveillance for MRSA BSI as a step towards a comprehensive surveillance programme in England.
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Antimicrobial resistance of major clinical pathogens in South Korea, May 2016 to April 2017: first one-year report from Kor-GLASS
The Korean government established an antimicrobial resistance (AMR) surveillance system, compatible with the Global AMR Surveillance System (GLASS): Kor-GLASS. We describe results from the first year of operation of the Kor-GLASS from May 2016 to April 2017, comprising all non-duplicated clinical isolates of major pathogens from blood, urine, faeces and urethral and cervical swabs from six sentinel hospitals. Antimicrobial susceptibility tests were carried out by disk diffusion, Etest, broth microdilution and agar dilution methods. Among 67,803 blood cultures, 3,523 target pathogens were recovered. The predominant bacterial species were Escherichia coli (n = 1,536), Klebsiella pneumoniae (n = 597) and Staphylococcus aureus (n = 584). From 57,477 urine cultures, 6,394 E. coli and 1,097 K. pneumoniae were recovered. Bloodstream infections in inpatients per 10,000 patient-days (10TPD) were highest for cefotaxime-resistant E. coli with 2.1, followed by 1.6 for meticillin-resistant Sta. aureus, 1.1 for imipenem-resistant Acinetobacter baumannii, 0.8 for cefotaxime-resistant K. pneumoniae and 0.4 for vancomycin-resistant Enterococcus faecium. Urinary tract infections in inpatients were 7.7 and 2.1 per 10TPD for cefotaxime-resistant E. coli and K. pneumoniae, respectively. Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. A bacterial bank and a database for the collections are under development.
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Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016
Surveillance plays a pivotal role in overcoming antimicrobial resistance (AMR) in bacterial pathogens, and a variety of surveillance systems have been set up and employed in many countries. In 2015, the World Health Organization launched the Global Antimicrobial Resistance Surveillance System (GLASS) as a part of the global action plan to enhance national and global surveillance and research. The aims of GLASS are to foster development of national surveillance systems and to enable collection, analysis and sharing of standardised, comparable and validated data on AMR between different countries. The South Korean AMR surveillance system, Kor-GLASS, is compatible with the GLASS platform and was established in 2016 and based on the principles of representativeness, specialisation, harmonisation and localisation. In this report, we summarise principles and processes in order to share our experiences with other countries planning to establish a national AMR surveillance system. The pilot operation of Kor-GLASS allowed us to understand the national burden of specific infectious diseases and the status of bacterial AMR. Issues pertaining to high costs and labour-intensive operation were raised during the pilot, and improvements are being made.
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Genomic epidemiology of meticillin-resistant Staphylococcus aureus ST22 widespread in communities of the Gaza Strip, 2009
BackgroundRemarkably high carriage prevalence of a community-associated meticillin-resistant Staphylococcus aureus (MRSA) strain of sequence type (ST) 22 in the Gaza strip was reported in 2012. This strain is linked to the pandemic hospital-associated EMRSA-15. The origin and evolutionary history of ST22 in Gaza communities and the genomic elements contributing to its widespread predominance are unknown. Methods: We generated high-quality draft genomes of 61 ST22 isolates from Gaza communities and, along with 175 ST22 genomes from global sources, reconstructed the ST22 phylogeny and examined genotypes unique to the Gaza isolates. Results: The Gaza isolates do not exhibit a close relationship with hospital-associated ST22 isolates, but rather with a basal population from which EMRSA-15 emerged. There were two separate resistance acquisitions by the same MSSA lineage, followed by diversification of other genetic determinants. Nearly all isolates in the two distinct clades, one characterised by staphylococcal cassette chromosome mec (SCCmec) IVa and the other by SCCmec V and MSSA isolates, contain the toxic shock syndrome toxin-1 gene. Discussion: The genomic diversity of Gaza ST22 isolates is not consistent with recent emergence in the region. The results indicate that two divergent Gaza clones evolved separately from susceptible isolates. Researchers should not assume that isolates identified as ST22 in the community are examples of EMRSA-15 that have escaped their healthcare roots. Future surveillance of MRSA is essential to the understanding of ST22 evolutionary dynamics and to aid efforts to slow the further spread of this lineage.
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Epidemiology and resistance phenotypes of carbapenemase-producing Klebsiella pneumoniae in Greece, 2014 to 2016
Irene Galani , Ilias Karaiskos , Irene Karantani , Vassiliki Papoutsaki , Sofia Maraki , Vassiliki Papaioannou , Polyzo Kazila , Helen Tsorlini , Nikoletta Charalampaki , Marina Toutouza , Helen Vagiakou , Konstantinos Pappas , Anna Kyratsa , Konstantina Kontopoulou , Olga Legga , Efthymia Petinaki , Helen Papadogeorgaki , Efrosini Chinou , Maria Souli , Helen Giamarellou and on behalf of the study collaboratorsBackground and aimA multicentre nationwide surveillance study was conducted in Greek hospitals to evaluate epidemiology of carbapenemase-producing Klebsiella pneumoniae clinical isolates, and their susceptibilities to last-line antibiotics. Methods: Minimum inhibitory concentrations (MICs) were evaluated by Etest, colistin MICs were also evaluated by broth microdilution SensiTest (now known as ComASP) Colistin. Carbapenemase genes were detected by PCR. Clonal relatedness was assessed by PFGE. Isolates were prospectively collected between November 2014 and April 2016, from 15 hospitals. Results: Among 394 isolates, K. pneumoniae carbepenemase (KPC) remained the most prevalent carbapenemase (66.5%). NDM was the second most prevalent (13.7%), identified in 12 hospitals, followed by VIM (8.6%). OXA-48- and double carbapenemase-producers remained rare (3.6%, 6.3%, respectively). Carbapenemase-producing K. pneumoniae isolates showed high resistance to last-line antibiotics. Gentamicin and colistin were the most active in vitro with 61.9% and 59.6% of the isolates to be inhibited at ≤ 2mg/L, followed by fosfomycin (susceptibility (S): 58.4%) and tigecycline (S: 51.5%). Ceftazidime/avibactam inhibited 99.6% of KPC and 100% of OXA-48-like-producing isolates, while temocillin was active against 58% of KPC isolates at urinary breakpoint of ≤ 32mg/L* and only 2.7% at systemic breakpoint of ≤ 8mg/L. NDM-producing isolates belonged mainly to one clone, whereas KPC, VIM, OXA-48 and double carbapenemase-producers were mainly polyclonal. Conclusions: KPC remains the predominant carbapenemase among K. pneumoniae in Greece, followed by NDM, whereas changing trends of resistance rates to last-line antimicrobials against carbapenemase-producing K. pneumoniae with the exception of ceftazidime/avibactam mandates continuing surveillance to support clinical practice.
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Risk factors for colistin-resistant Enterobacteriaceae in a low-endemicity setting for carbapenem resistance – a matched case–control study
More LessBackgroundEmergence of colistin resistance has been related to increased use in clinical settings, following global spread of carbapenem-resistant Gram-negative bacteria. Use of colistin in animal production may constitute a further source of spread of resistant strains to humans. We sought to determine risk factors for human colonisation or infection with colistin-resistant Escherichia coli and Klebsiella pneumoniae in a setting where colistin is mainly used for animal production. Methods: This retrospective matched case–control study was performed during a 5-year period at two university-affiliated hospitals in Basel, Switzerland. Conditional univariable logistic regression was used to calculate odds ratios (OR) for colistin resistance. All variables found to be significant in univariable analyses were included in the conditional multivariable regression model using stepwise forward and backward selection. Results: Forty-two cases (33 with colistin-resistant E. coli, 9 with colistin-resistant K. pneumoniae) and 126 matched controls were identified. Baseline characteristics, comorbidities, prior exposure to antibiotics and healthcare settings did not differ between cases and controls, except for prior exposure to carbapenems, hospitalisation and stay abroad during the prior 3 months. In multivariable analyses, only prior exposure to carbapenems remained associated with colistin resistance (OR: 5.00; 95% confidence interval (95% CI): 1.19–20.92; p = 0.028). Conclusion: In a low-endemicity setting for carbapenem resistance, prior exposure to carbapenems was the only risk factor for colonisation or infection with colistin-resistant E. coli or K. pneumoniae. Prior exposure to colistin was not significantly associated with detection of colistin resistance, which mainly occurred in the absence of concurrent carbapenem resistance.
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Outbreak of vancomycin-resistant Enterococcus faecium clone ST796, Switzerland, December 2017 to April 2018
A large outbreak of vancomycin-resistant enterococci (VRE) is affecting four hospitals in the Canton of Bern, Switzerland, since December 2017. Of 89 cases identified as carriers, 77 (86.5%) VRE isolates were virtually indistinguishable using whole genome sequencing, and identified as multilocus sequence type (MLST) ST796. This clone, previously only described in Australia and New Zealand, is characterised by rapid spread and the ability to cause bloodstream infections. It requires a multifaceted infection prevention effort.
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Comparing antibiotic consumption between two European countries: are packages an adequate surrogate for prescriptions?
More LessDefined daily doses (DDD) are the gold standard indicator for quantifying prescriptions. Since 2014, the European Centre for Disease Prevention and Control (ECDC) has also been using the number of packages per 1,000 inhabitants per day (ipd), as a surrogate for prescriptions, to report antibiotic consumption in the community and to perform comparisons between European Union (EU) countries participating in the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In 2015, consumption was reported to range across Europe from 1.0 to 4.7 packages per 1,000 ipd. Our analysis showed that consumption of antibiotics for systemic use per 1,000 ipd was on average 1.3 times greater in France than in Belgium when considering prescriptions in the numerator, 2.5 times greater when considering packages and 1.2 times greater when considering DDD. As long as the same metrics are used over time, antibiotic consumption data aggregated and disseminated by ECDC are useful for assessing temporal trends at the European level and within individual countries; these data may also be used for benchmarking across EU countries. While DDD - although imperfect - are the most widely accepted metric for this purpose, antibiotic packages do not appear suitable for comparisons between countries and may be misleading.
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National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands
An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data.
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Livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) among human MRSA isolates, European Union/European Economic Area countries, 2013
Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa-typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance.
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Use of WHONET-SaTScan system for simulated real-time detection of antimicrobial resistance clusters in a hospital in Italy, 2012 to 2014
More LessResistant pathogens infections cause in healthcare settings, higher patient mortality, longer hospitalisation times and higher costs for treatments. Strengthening and coordinating local, national and international surveillance systems is the cornerstone for the control of antimicrobial resistance (AMR). In this study, the WHONET-SaTScan software was applied in a hospital in Italy to identify potential outbreaks of AMR. Data from San Filippo Neri Hospital in Rome between 2012 and 2014 were extracted from the national surveillance system for antimicrobial resistance (AR-ISS) and analysed using the simulated prospective analysis for real-time cluster detection included in the WHONET-SaTScan software. Results were compared with the hospital infection prevention and control system. The WHONET-SaTScan identified 71 statistically significant clusters, some involving pathogens carrying multiple resistance phenotypes. Of these 71, three were also detected by the hospital system, while a further 15, detected by WHONET-SaTScan only, were considered of relevant importance and worth further investigation by the hospital infection control team. In this study, the WHONET-SaTScan system was applied for the first time to the surveillance of AMR in Italy as a tool to strengthen this surveillance to allow more timely intervention strategies both at local and national level, using data regularly collected by the Italian national surveillance system.
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Risk-adjusted antibiotic consumption in 34 public acute hospitals in Ireland, 2006 to 2014
More LessAs antibiotic consumption rates between hospitals can vary depending on the characteristics of the patients treated, risk-adjustment that compensates for the patient-based variation is required to assess the impact of any stewardship measures. The aim of this study was to investigate the usefulness of patient-based administrative data variables for adjusting aggregate hospital antibiotic consumption rates. Data on total inpatient antibiotics and six broad subclasses were sourced from 34 acute hospitals from 2006 to 2014. Aggregate annual patient administration data were divided into explanatory variables, including major diagnostic categories, for each hospital. Multivariable regression models were used to identify factors affecting antibiotic consumption. Coefficient of variation of the root mean squared errors (CV-RMSE) for the total antibiotic usage model was very good (11%), however, the value for two of the models was poor (> 30%). The overall inpatient antibiotic consumption increased from 82.5 defined daily doses (DDD)/100 bed-days used in 2006 to 89.2 DDD/100 bed-days used in 2014; the increase was not significant after risk-adjustment. During the same period, consumption of carbapenems increased significantly, while usage of fluoroquinolones decreased. In conclusion, patient-based administrative data variables are useful for adjusting hospital antibiotic consumption rates, although additional variables should also be employed.
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Antibiotic prescribing and expenditures in outpatient adults in Greece, 2010 to 2013: evidence from real-world practice
We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad-spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing.
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Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003–2010
This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003–2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003–2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003–2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden.
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Analysis of licensed over-the-counter (OTC) antibiotics in the European Union and Norway, 2012
More LessAntimicrobial resistance is recognised as a growing problem that seriously threatens public health and requires prompt action. Concerns have therefore been raised about the potential harmful effects of making antibiotics available without prescription. Because of the very serious concerns regarding further spread of resistance, the over-the-counter (OTC) availability of antibiotics was analysed here. Topical and systemic OTC antibiotics and their indications were determined across 26 European Union (EU) countries and Norway by means of a European survey. We identified a total of 48 OTC products containing 20 different single antibiotics and three antibiotic combinations as active substances, used mainly as topical preparations in short treatment courses. Given the relevance of these medicines and the increasing risk of antimicrobial resistance, it is important to limit the availability of OTC antibiotics and to monitor their use.
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European Antibiotic Awareness Day: a five-year perspective of Europe-wide actions to promote prudent use of antibiotics
S Earnshaw , G Mancarella , A Mendez , B Todorova , A P Magiorakos , E Possenti , M Stryk , S Gilbro , H Goossens , B Albiger , D L Monnet , collective on behalf of the European Antibiotic Awareness Day Technical Advisory Committee and collective on behalf of the European Antibiotic Awareness Day Collaborative GroupFollowing the European Union (EU) Council Recommendation on prudent use of antimicrobial agents in human medicine in 2001, and the success of national campaigns, i.e. Belgium and France, the European Centre for Disease Prevention and Control (ECDC) decided to establish the European Antibiotic Awareness Day (EAAD) on 18 November as platform to support national campaigns across Europe. This article provides an overview of EAAD tools, materials, and activities developed during the first five years. It shows that EAAD has been successful due to good cooperation between ECDC and national institutions, strong political and stakeholder support and evidence-based development of campaign materials. EAAD has provided a platform for pre-existing national campaigns and encouraged similar campaigns to develop where neither political support had been secured, nor financial support had been available. As a result, participating countries have continuously expressed strong support for ECDC to continue its work on EAAD. This has been endorsed by a steadily increasing number of countries participating and the growing interest of varied professional and stakeholder organisations. We conclude that EAAD should continue to act as catalyst for discussion and as mechanism to raise awareness of the public and prescribers about prudent use of antibiotics.
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Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone
S A Chisholm , M Unemo , N Quaye , E Johansson , M J Cole , C A Ison and M JW Van de LaarTreatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in ≥two isolates. Seven major genogroups of closely related STs (varying by ≤1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.
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