«ECDC SPECIAL REPORT Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe This report of the ...»
Response plan to control and
manage the threat of multidrugresistant gonorrhoea in Europe
ECDC SPECIAL REPORT
Response plan to control and manage the
threat of multidrug-resistant gonorrhoea
This report of the European Centre for Disease Prevention and Control (ECDC) was coordinated and produced by Gianfranco
Spiteri and Marita van de Laar, Programme for STIs, including HIV/AIDS and blood-borne infections.
Acknowledgements We wish to thank the members of the ECDC expert group for the multidrug-resistant gonorrhoea response plan who have
contributed to excellent discussions at the expert group meeting on 18 October 2011 and to the preparations of this report:
Experts in the STI microbiology project: Stephanie Chisholm; Michelle Cole; Cathy Ison (all Health Protection Agency, • United Kingdom); Steen Hoffmann, Statens Serum Institute, Denmark; Magnus Unemo, Örebro University Hospital, Sweden;
Members of the STI coordination group: Osamah Hamouda, Robert Koch Institute, Germany; Gwenda Hughes, Health • Protection Agency, United Kingdom; Vasileia Konte, Hellenic Center for Disease Control and Prevention, Greece; Angelika Stary, Ambulatorium für Pilzinfektionen und andere infektiöse venerodermatologische Erkrankungen, Austria; Paola Stefanelli, Istituto Superiore di Sanità, Italy; Inga Velicko, Swedish Institute for Infectious Disease Control, Sweden;
Invited experts: Chris Bignell, International Union against Sexually Transmitted Infections; Francis Ndowa, World Health • Organization, Geneva; Airi Poder, International Union against Sexually Transmitted Infections.
We also wish to thank the members in the European STI Network for fruitful discussions during the annual STI/HIV network meeting, Stockholm, Sweden, 15 to 16 February 2012.
Contributing ECDC staff: Aino-Maija Aikkinen, Dominique Monnet; Otilia Sfetcu; Marc Struelens Suggested citation: European Centre for Disease Prevention and Control. Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe. Stockholm: ECDC; 2012.
Stockholm, June 2012 ISBN 978-92-9193-375-4 doi 10.2900/60053 Cover photo: © Nathan Reading © European Centre for Disease Prevention and Control, 2012 Reproduction is authorised, provided the source is acknowledged.
SPECIAL REPORT Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe Contents Abbreviations
Resistance in gonorrhoea
European Gonococcal Antimicrobial Surveillance Programme
Public health response
Objectives of the response plan
Components of the response plan
1 Strengthening antimicrobial surveillance
1.1 A strategy for expanding Euro-GASP
1.2 National antimicrobial surveillance
1.4 Improving data completeness and timeliness
2 Clinical management and treatment failure monitoring
2.1 Clinical management
2.2 Case definitions for antibiotic treatment failure
2.3 Mechanisms for reporting of treatment failures
3 Communication strategy
4 Monitoring the effectiveness of the response plan
Annex 1. Template for report of treatment failure
Annex 2. Letter to clinicians
Annex 3. Facts in brief
Annex 4: Fact sheet
iv SPECIAL REPORT Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe Background Resistance in gonorrhoea With 32 028 cases, gonorrhoea was the second most commonly reported bacterial STI in Europe in 2010 .
Gonorrhoea is a serious public health problem as untreated infections may lead to severe secondary sequelae, including pelvic inflammatory disease, first trimester abortions, ectopic pregnancy, and infertility .
N. gonorrhoeae infections also play a role in facilitating HIV transmission . The average cost per case of gonorrhoea has been estimated to be 266 USD for women and 53 USD for men . Successful treatment of cases reduces the risk of complications, but also serves as the main public health strategy for reducing transmission.
Over the past decades, N. gonorrhoeae has developed resistance to several antimicrobial drugs such as sulphonamides, penicillin, tetracyclines and quinolones. Current treatment guidelines in most European countries recommend the use of single-dose injectable (ceftriaxone) or oral (cefixime) third-generation cephalosporins .
The first treatment failures connected to less potent third-generation cephalosporins were reported in Japan in 2000 . Subsequently, further cases of treatment failure were reported from other countries . A recent report described the first two treatment failures with cefixime in the EU/EEA (2010 in Norway ), followed by three cases of treatment failure in England [9, 10] and one case in Austria in 2011 . The recent report of a highly ceftriaxone-resistant N. gonorrhoeae strain H041 in Japan  triggered worldwide concerns as ceftriaxone is the last remaining option for empirical first-line treatment. Ceftriaxone treatment failure of pharyngeal gonorrhoea  has been recently reported in Sweden; the first case of genital infection of highly ceftriaxone-resistant N. gonorrhoeae in Europe was reported in France in 2011 . A suspected ceftriaxone-resistant strain has also been reported from Spain . The in vitro susceptibility to cefixime has also rapidly decreased, and results from the European gonococcal antimicrobial surveillance programme (Euro-GASP) show that susceptibility to ceftriaxone is decreasing [16-19]. N. gonorrhoeae also seems to retain resistance to several classes of antimicrobials, even when the antimicrobials in question were discontinued.
In recent years, nucleic acid amplification tests (NAATs) have increasingly been replacing culture as a diagnostic test for gonorrhoea across Europe. Although NAATs are generally more sensitive and quicker than culture, this has resulted in the loss of expertise and capacity in a number of countries to perform culture and antimicrobial resistance (AMR) testing. This move towards an increased use of NAATs has therefore resulted in a lack of AMR data in a number of EU/EEA countries. The lack of use of commercially available transport medium which is suitable both for NAAT and culture retrieval is of serious concern and jeopardises the possibility of producing national AMR profiles for gonococci to inform treatment guidelines.
This lack of AMR data implies that national authorities and professional medical associations may not be able to develop appropriate treatment guidelines for gonorrhoea. This is particularly relevant when alternative therapies for cephalosporin-resistant N. gonorrhoeae are becoming more and more limited.
European Gonococcal Antimicrobial Surveillance Programme The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) has been set up to inform public health and treatment guidelines on AMR testing results in EU/EEA countries and reports on trends in gonococcal AMR across Europe . These data are crucial for optimisation of treatment and to detect emerging resistance.
Euro-GASP is implemented as a sentinel surveillance system through the European STI expert network and involves a network of laboratories in Member States. Euro-GASP includes AMR testing twice a year, an external quality assessment programme, and training for laboratory staff.
Table 1 shows the main results from Euro-GASP 2010. The most worrying result is the increase in the percentage of isolates with decreased susceptibility to cefixime and the increase in the number of countries where this phenotype was identified between 2009 and 2010. Patient characteristics of isolates with decreased susceptibility did not differ greatly when compared to the overall population, except for age: patients with decreased susceptibility to cefixime were more likely to be older. Rates of ciprofloxacin and azithromycin resistance have both decreased since 2009, but remain high across Europe (53% and 7%, respectively). Between 2009 and 2011, the external quality assessment programme has consistently shown high comparability between participants, which in turn gives confidence with respect to gonococcal antimicrobial susceptibility data from Euro-GASP .
Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe SPECIAL REPORT
Figure 1: Decreased susceptibility to cefixime (MIC 0.12mg/L) and reported cefixime treatment failures, 2010 No decreased susceptibility
Reports of treatment failures 2010 (5), 2011 (2) The rapid increase and spread of decreased susceptibility to cefixime is extremely concerning as this is a recommended therapy for gonorrhoea across Europe, as is ceftriaxone. Euro-GASP has also detected increases from 2009 onwards in the higher MIC categories for ceftriaxone, which could be due to the molecular mechanisms that confer decreased susceptibility to cefixime also conferring decreased susceptibility to ceftriaxone. The lack of alternative therapies, decreasing susceptibility to the cephalosporins, and numbers of treatment failures across Europe show that the gonococcal population needs to be monitored carefully, and a European public health response plan needs to be developed, as the loss of both cefixime and ceftriaxone as treatment options for gonorrhoea would have a significant impact on public health.
SPECIAL REPORT Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe Public health response Objectives of the response plan This response plan is designed to contribute to preventing the spread of multidrug-resistant Neisseria gonorrhoeae (MDR NG) in the EU/EEA in the context of the possible emergence of untreatable gonorrhoea. MDR NG is defined as by Tapsall et al . The plan details the response at European level and is designed as a guide for Member States when planning national interventions.
The main goal of the public health response plan is to minimise the impact of MDR NG on the prevention and control of gonorrhoea in Europe.
Specific objectives include:
Strengthening the surveillance of gonococcal antimicrobial susceptibility in the EU/EEA Member States to • inform national treatment guidelines;
Ensuring that a minimum capacity for culture and susceptibility testing in EU/EEA Member States is either • available or developed;
Establishing a strategy to rapidly detect patients diagnosed with gonorrhoea who experience a clinical • treatment failure following treatment with recommended cephalosporins, including the clinical management of affected patients and their sexual partners;
Outlining a set of recommended public health actions to be implemented at the national level, following the • detection of MDR NG cases; and Increasing the awareness of policy makers, clinicians, patients, and key populations.
• Components of the response plan The response plan strives to support Member States to develop and implement national interventions to control the threat of multidrug-resistant gonorrhoea in a multidisciplinary approach. The public health response has the
Strengthening surveillance to obtain AMR profiles in a timely manner and with sufficient epidemiological • information to inform national interventions;
Implementing treatment failure monitoring to inform national and international authorities and professional • societies in order to develop treatment guidelines and design national interventions; and Establishing a communication strategy to increase awareness and disseminate the results from AMR • surveillance in order to inform authorities, professional societies, physicians, and potential patients about the threat of multidrug-resistant gonorrhoea.
Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe SPECIAL REPORT 1 Strengthening antimicrobial surveillance
1.1 A strategy for expanding Euro-GASP It is imperative that AMR testing results for N. gonorrhoeae isolates are obtained from all EU/EEA countries to inform the AMR profiles to be able to develop appropriate treatment guidelines. Given the movement of strains across Europe, a Europe-wide approach is essential in order to detect and monitor resistant strains and thus informs European treatment guidelines. Appropriate treatment must be administered to ensure successful patient management and to interrupt transmission. Without proper N. gonorrhoeae AMR data it is difficult to ascertain whether the correct treatment options are available in a country; inappropriate treatment can lead to the emergence of resistance, increased patient morbidity, increased acquisition of HIV, and an overall bigger cost burden to the healthcare system.
In 2011, 21 out of 30 EU/EEA countries participated in Euro-GASP. The reasons for non-participation are primarily the lack of available cultures to refer to Euro-GASP (due to the use of NAATs), the differences in diagnostic procedures in STI clinics, and the lack of resources for performing culture. Participation from central and eastern EU/EEA countries should be improved, as very limited information is available on the AMR profile in these countries.
In some countries, antimicrobial drugs seem to be easily available without prescription and the use of suboptimal medication as a second-line treatment seems to be common . These factors increase the risk of emergence of MDR NG. Expanding Euro-GASP to more countries is therefore important to further control emergence and spread of MDR NG strains in Europe.