Antimicrobial resistance (AMR) in  N. gonorrhoeae  (GC)   - global problem but valid data are lacking in many geographic a...
GC AMR surveillance is crucial for  public health purposes! <ul><ul><li>Gonorrhoea soon untreatable  due to the high and i...
    (  ) GISP EURO- GASP RU- GASP    !  (  ) !  WHO SEARO WHO WPRO   Global surveillance of GC AMR possible? ...
<ul><li>June – August </li></ul><ul><li>110 consecutive gonococcal isolates collected </li></ul><ul><li>Basic Demographics...
Overall incidence of resistant  GC 2004, 2006 and 2007 Recommended threshold  for exclusion:  5% R in general population
Ciprofloxacin resistance in  2004 (n=12 countries) and 2007 (n=14) 2004:  Martin I, et al. 2006. J Antimicrob Chemother: 5...
Ceftriaxone minimum inhibition concentration (MIC) distribution in EURO-GASP 2004 and 2007 2004 2007 <ul><li>Endpoint MIC?...
Problems   -  many different antimicrobials  used for treatment -  poor quality  of many of the antimicrobials - valid  re...
Russian Gonococcal antimicrobial susceptibility program  (RU-GASP):  initiated in 2004 at  CNIKVI, Health Ministry, Moscow...
Resistance in Russia in 2005-2007 2005-2006:  Kubanova A, et al. 2008. Sex Transm Infect. 84:285-9;  2007:  Kubanova A, et...
“ In Russia,  penicillins, ciprofloxacin, or tetracycline should definitively not be used   in empirical treatment  of gon...
<ul><li>Resistance to traditional antimicrobials (penicillins, erythromycin, tetracyclines) and ciprofloxacin is exceeding...
RU- GASP             GC AMR surveillance in Eastern European Sexual and Reproductive Health (EE-SRH) Network c...
N. gonorrhoeae  diagnostic   guidelines for Eastern Europe (Now published in 10 EE-SRH Network countries!) <ul><li>Optimiz...
Possibilities to start in Belarus? <ul><li>Requirements! </li></ul><ul><li>Improved GC culture diagnostics </li></ul><ul><...
GC AMR surveillance in East-European countries, according to WHO protocols, i.e. in collaboration with the International R...
J Antimicrobial Chemother 2009, in press
Methods <ul><li>Phenotypic methods   </li></ul><ul><li>auxotyping, serovar determination, prolyliminopeptidase (PIP)-scree...
Results
<ul><li>The strains are useful for external (distributed as unknown in triplicates) and internal  Quality Assurance and Co...
Similar problems as in Eastern Europe:   - updated quality assured and quality controlled data needed! -  many different a...
GC   AMR in USA (GISP), South-East Asia (WHO SEARO),  Western Pacific (WHO WPRO) - the oldest, most ambitious and best wor...
Reference Laboratory (national and international) <ul><li>Provide support, expertise, and consultation: scientifical, labo...
 
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Antimicrobial resistance (AMR) in N. gonorrhoeae (GC) - global problem but valid data are lacking in many geographic areas

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Antimicrobial resistance (AMR) in N. gonorrhoeae (GC) - global problem but valid data are lacking in many geographic areas

Magnus Unemo, PhD, Assoc. Professor
Reference Laboratory for Pathogenic Neisseria
Department of Clinical Microbiology

Örebro University Hospital
Sweden

Published in: Health & Medicine, Technology
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  • Antimicrobial resistance (AMR) in N. gonorrhoeae (GC) - global problem but valid data are lacking in many geographic areas

    1. 1. Antimicrobial resistance (AMR) in N. gonorrhoeae (GC) - global problem but valid data are lacking in many geographic areas Magnus Unemo, PhD, Assoc. Professor Reference Laboratory for Pathogenic Neisseria Department of Clinical Microbiology Örebro University Hospital Sweden
    2. 2. GC AMR surveillance is crucial for public health purposes! <ul><ul><li>Gonorrhoea soon untreatable due to the high and increasing level of resistance? </li></ul></ul><ul><ul><li>Individual case management! </li></ul></ul><ul><ul><li>Inform local, national, and international guidelines for therapy ! </li></ul></ul><ul><ul><li>- Prevent the spread of infection! </li></ul></ul><ul><ul><li>Decrease the burden of infection! </li></ul></ul>
    3. 3.     (  ) GISP EURO- GASP RU- GASP    !  (  ) !  WHO SEARO WHO WPRO   Global surveillance of GC AMR possible? An attempt is in progress!
    4. 4. <ul><li>June – August </li></ul><ul><li>110 consecutive gonococcal isolates collected </li></ul><ul><li>Basic Demographics </li></ul>EURO-GASP (ESSTI; Cathy Ison and Michelle Cole, STBRL, HPA, UK), soon ECDC
    5. 5. Overall incidence of resistant GC 2004, 2006 and 2007 Recommended threshold for exclusion: 5% R in general population
    6. 6. Ciprofloxacin resistance in 2004 (n=12 countries) and 2007 (n=14) 2004: Martin I, et al. 2006. J Antimicrob Chemother: 587-93; 2007: ESSTI Annual Report No. 2, 2007 Ciprofloxacin resistance: 2004: 30.9% (7.6-53.1%)! 2007: 52.2 (20.3-90.3%)! Recommended threshold for exclusion: 5% R in general population
    7. 7. Ceftriaxone minimum inhibition concentration (MIC) distribution in EURO-GASP 2004 and 2007 2004 2007 <ul><li>Endpoint MIC? </li></ul><ul><li>New determinants needed for full </li></ul><ul><li>resistance and treatment failures? </li></ul><ul><li>Extended-spectrum  -lactamase (ESBL)? </li></ul><ul><li>” it may be more a matter of when and not if strains emerge that are </li></ul><ul><li>resistant to also ceftriaxone !” Lindberg R, et al. 2007. AAC: 2117-22 ” </li></ul>MIC 50 :
    8. 8. Problems - many different antimicrobials used for treatment - poor quality of many of the antimicrobials - valid resistance data exceedingly rare (due to use mainly of microscopy for diagnosis and overall rare use of AMR testing) - methodological problems and differences - high potentials for emergence of new resistance - treatment failures? - Large need of evalution, optimisation, and quality assurance of the AMR testing (as well as overall introduction of improved culture diagnostics and AMR testing in some countries)! AMR of GC and gonorrhoea treatment in Eastern Europe
    9. 9. Russian Gonococcal antimicrobial susceptibility program (RU-GASP): initiated in 2004 at CNIKVI, Health Ministry, Moscow Sex Transm Infect. 2008; 84:285-9
    10. 10. Resistance in Russia in 2005-2007 2005-2006: Kubanova A, et al. 2008. Sex Transm Infect. 84:285-9; 2007: Kubanova A, et. 2008. Submitted. Multiresistance common: 2007: 1.1% to all antimicrobials except ceftriaxone (PcG, tetracycline, ciprofloxacin, azithromycin, spectinomycin)!
    11. 11. “ In Russia, penicillins, ciprofloxacin, or tetracycline should definitively not be used in empirical treatment of gonorrhoea, i.e. if results from antibiotic susceptibility testing are not available. The recommended first-line antimicrobial should be ceftriaxone. If not access to ceftriaxone, spectinomycin ought to be used.” Kubanova A, et al. 2008. Sex Transm Infect. 84;285-9 New antimicrobial treatment recommendations for gonorrhoea in Russia:
    12. 12. <ul><li>Resistance to traditional antimicrobials (penicillins, erythromycin, tetracyclines) and ciprofloxacin is exceedingly high in most countries! </li></ul><ul><li>Azithromycin resistance has rapidly increased and is relatively high in many countries! </li></ul><ul><li>Resistance to spectinomycin is very rare but exists! </li></ul><ul><li>Rare strains with reduced suceptibility to cefixime and ceftriaxone have been identified! MICs are increasing! </li></ul><ul><li>Multiresistant strains are widespread! </li></ul>Reduced antimicrobial susceptibility and resistance of N. gonorrhoeae in Europe?
    13. 13. RU- GASP             GC AMR surveillance in Eastern European Sexual and Reproductive Health (EE-SRH) Network countries?
    14. 14. N. gonorrhoeae diagnostic guidelines for Eastern Europe (Now published in 10 EE-SRH Network countries!) <ul><li>Optimiz a tion, harmonization and quality assurance! Eastern European Sexual and Reproductive Health (EE-SRH) network (www.medsci.uu.se/klinbakt/Stigup/Projects, Project coordinator: Marius Domeika) </li></ul>
    15. 15. Possibilities to start in Belarus? <ul><li>Requirements! </li></ul><ul><li>Improved GC culture diagnostics </li></ul><ul><li>Quality assured GC AMR testing </li></ul><ul><li>Preservation of GC strains </li></ul><ul><li>Reference laboratory (or equivalent) in collaboration with the International Reference Lab. and EE-SRH Network </li></ul><ul><li>Interest, careful work and ambition! </li></ul>
    16. 16. GC AMR surveillance in East-European countries, according to WHO protocols, i.e. in collaboration with the International Reference Laboratory and through the EE-SRH Network? Solutions! <ul><ul><li>  </li></ul></ul><ul><li>WHO and EE-SRH GC diagnostic guidelines! </li></ul><ul><li>WHO GC AMR Surveillance Standards (updated in 2008)! </li></ul><ul><li>WHO Reference methodology! </li></ul><ul><li>2008 WHO GC Reference strains (launched in 2008) for quality assurance and quality control! (Documents soon available also in Russian and WHO reference strains can be provided!) </li></ul>
    17. 17. J Antimicrobial Chemother 2009, in press
    18. 18. Methods <ul><li>Phenotypic methods </li></ul><ul><li>auxotyping, serovar determination, prolyliminopeptidase (PIP)-screening,  -lactamase production </li></ul><ul><li>Etest for MIC determination of penicillin G, ampicillin, cefuroxime, cefixime, ceftriaxone, ertapenem, erythromycin, azithromycin, ciprofloxacin, spectinomycin, kanamycin, gentamicin, rifampicin, and tetracycline </li></ul><ul><li>Genetic methods </li></ul><ul><li>- sequencing of resistance determinants, i.e. penA, mtrR, porB, ponA, gyrA, parC, parE, 16S rDNA, rpoB </li></ul><ul><li>multiplex real-time PCRs for typing of the  -lactamase plasmids and tet M plasmids </li></ul><ul><li>- full-length porB sequencing and NG-MAST (molecular epidemiology) </li></ul>
    19. 19. Results
    20. 20. <ul><li>The strains are useful for external (distributed as unknown in triplicates) and internal Quality Assurance and Control of genetic and phenotypic AMR testing using agar dilution, Etest, and disc diffusion of most antimicrobials of interest </li></ul><ul><li>Resistance phenotype detection valid and comparable for each method </li></ul><ul><li>HOWEVER, must precisely use the nominated method (media, reagents, incubation, etc.) </li></ul><ul><li>Will be widely available from mainly WHO sources </li></ul>Conclusions
    21. 21. Similar problems as in Eastern Europe: - updated quality assured and quality controlled data needed! - many different antimicrobials used for treatment! - poor quality of many of the antimicrobials! - valid recent resistance data rare! - methodological problems and differences! - high potentials for emergence of new resistance! - Coordinated approaches needed and in progress! AMR of GC in Africa; Eastern-Mediterranean region (EMRO); Caribbean, Central and South America
    22. 22. GC AMR in USA (GISP), South-East Asia (WHO SEARO), Western Pacific (WHO WPRO) - the oldest, most ambitious and best working GC AMR surveillance systems! - however, all systems have limitations such as representativeness, limited no. of specimens, identification of local AMR prevalence, etc. - GISP: mainly similar resistance problems as in Europe! - WHO SEARO: highest level of resistance and probably the most important region because most of the resistances emerge there (low control of infection and the no. as well as quality of antimicrobials used)!
    23. 23. Reference Laboratory (national and international) <ul><li>Provide support, expertise, and consultation: scientifical, laboratory and clinical advices (difficult cases), technical, quality assurance panels, e.g. reference strains or sera </li></ul><ul><li>International broad “front-line” research (basic e.g. describing mechanisms and developing new assays, laboratory including evaluation of diagnostic assays, clinical and epidemiological, etc.) </li></ul><ul><li>Development </li></ul><ul><li>Education including capacity building, training, transfer of technology </li></ul><ul><li>Guidelines (prevention, diagnostics, surveillance, typing, treatment) and annual national and international reports </li></ul><ul><li>International activities: as above but also attendance at congresses, involvement in collaboration surveillance and research groups, etc. </li></ul><ul><li>Decades of tradition and experience highly important but you always have to start from scratch! </li></ul><ul><li>Improved GC culture diagnostics </li></ul><ul><li>Quality assured GC AMR testing </li></ul><ul><li>Preservation of GC strains </li></ul><ul><li>Reference laboratory (or equivalent) with connection to the International Reference Lab. and EE-SRH Network </li></ul><ul><li>Interest, careful work and ambition! </li></ul>

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