Nye retningslinjer for behandling av gonoré

Transkript

1 Nye retningslinjer for behandling av gonoré Harald Moi Olafiaklinikken Oslo Universitetssykehus Medisinsk fakultet Universitetet i Oslo

2 Neisseria gonorrhoea Gonoré Inkubasjonstid 2-3 dager, lengre hos kvinner Asymptomatisk hos 50% kvinner og 10-20% menn De fleste menn får uretritt med betydelig utflod (dryppert) Smitte i hals og anus ofte uten symptomer

3 Når ta prøve for gc? Symptomatisk Svær uretritt/cervicitt Epidemiologisk MSM Smitteoppsporing Sex høyendemiske land indekspas eller partner Prøvetaking for dyrkning MSM fra uretra, anus, hals Heterosex menn: uretra Kvinner med mistanke på gc Cervix, uretra, hals, (anus) Fra hals og anus hvis mulig NAAT Hvis pos NAAT før behandling: Ta dyrking i tillegg

4 Mikroskopi

5 Mikroskopi

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7 Behandling av gonoré 1930: sulfonamider : penicillin 1970: Amoxicillin kombinert med probenecid : Tetracycliner : Ciprofloxacin : Makrolider 2000: 3 generasjons cefalosporiner Ceftriaxone i.m mg Cefixime 400 mg p.o. 2011: Ceftriaxone 500 mg i.m. Spektinomycin 2 g i.m.

8 Resistensutvikling : Økende kromosomal resistens mot penicillin 1976: Påvist penicillinase produserende plasmid (PPNG) 4,4 Mda Asia, 3,2 Mda Afrika, 3,05 Mda Toronto (Rio, Nimes, New Zealand 1980: Høygradig plasmidmediert tetracyklinresistens (TRNG) TRNG-A: Amerika type, TRNG-D: Dutch type 1990: Økende fluoro-kinolonresistens 2003: Cefixime resistens i Japan Shigeaki Yokoi et al. Threat to Cefixime Treatment for Gonorrhea.Emerg Infect Dis August; 13(8): : Cefixime resistens i Oslo Unemo M, Golparian D, Syversen G, Vestrheim DF, Moi H.Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment, Norway, 2010.Euro Surveill Nov 25; : Cefixime og azitromycin resistens i UK C A Ison, J Hussey, K N Sankar, J Evans, S Alexander. Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010.Eurosurveillance, Volume 16, Issue 14, 07 April 2011

9 Resistens i Norge MSIS 208 tilfeller 126(61%) resistente gonokokker. 31 beta-laktamaseproduserende gonokokker 51 kinolonresistente gonokokker 44 gonokokker med begge resistens-former 200 stammer fra 2009 undersøkt 80% I eller R for kinoloner

10 Unemo M, Golparian D, Hestner A. Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010.Euro Surveill Feb 10;16(6).

11 Behandlingavgonoré Primær behandling må ha minst 95% effekt (WHO) Behandling før resistenssvar Ceftriaxone500 mg im 1 grams ampulle tilsettes 3,5 ml xylocain10 mg/ml uten adrenalin. Blandes og trekkes opp 2 ml Behandling etter resistenssvar Kan ta over 1 uke Hvis følsom i resistensbestemmelse: Ciprofloksacin 500 mg po Amoxicillin1 gram x 2 med 5 timers mellomrom Bør faryngealgcbehandles med 1 gram ceftriaxone?

12 Spectinomycin Mangel på spectinomycin i verdensmarkedet 2 gram i.m. effektiv mot gc i uretra, anus og cervix. Dårlig effekt mot faryngeal gc Tyktflytende, vanskelig å injisere Resistens ikke sett i Norge

13 Tidsskriftet 7/2011: Gonoré på tide med nye retningslinjer UHartgill IJakopanec DFVestrheim Anbefaling: Ceftriaxone mg i.m. Antibiotikaveileder for primærhelsetjenesten: Ceftriaxone 500 mg i.m. UK anbefaling: Ceftriaxone 500 mg i.m. pluss 1 gram Azitromycin

14 Treatment of Mycoplasmagenitalium Open prospective Scandinavian multicenter study (Björnelius et al. 2008) Doxycyclin 200 mg x mg x 1 x 8: 22% cure rate Azithromycin 1 g x 1: 86% cure rate Azithromycin 500 mg mg x 1 x 4: 97% cure rate Randomized study USA (Mena et al. CID 2009) Doxycyclin 200 mg x 1 x 7: 45% cure rate Azithromycin 1 g x 1: 87% cure rate Clinical efficacy in DOX group by 2-3 week control, but later recurrence Open retrospective Norwegian study (Jernberg et al 2008) Azithromycin 1g x 1: 79% cure rate Azithromycin 500 mg mg x 1 x 4: 78% cure rate Ofloxacin: 200 mg x 2 for 10 days: 44% cure rate Moxifloxacin: 400 mg x 1 for 7 days: 100% cure rate

15 Mycoplasmagenitaliumtreatment Antibiotic Treatment efficacy Tetracyclin/Doxycyclin 20-45% Azithromycin 1g x % Azithromycin 500 mg day mg day 2-5 Ciprofloxacin, ofloxacin, levofloxacin 75-95% 30-55% Moxifloxacin >99%

16 Mycoplasma genitaliummacrolide resistence Mutations in region V of 23S rdna causes macrolide resistence Assay for detection of the resistence mutations direct from clinical samples developed 19 patients with positive MG PCR before and after treatment Treated with Azthromycin 1g x 1 16 (84%) had wild-type (WT macrolide susceptible type) before treatment All 16 had macrolide mutation after treatment Drug resistance was induced as the result of an inappropriate dosage of azithromycin Jensen et al., CID 2008

17 Mycoplasmagenitalium makrolide resistence

18 Mycoplasma genitalium macrolide resistance Is high initial DNA load associated with treatment failure? Spontaneous mutations in 23 S rdnaare probably natural occurring, but a biological unfit without selection. Could resistance problems be decreased by lowering the selection pressure? Wide use of Azithromycin is selecting the mutation gene Guschin, IUSTI 2009

19 Experience from Nordic countries 181 M. genitaliumpositive Swedish STD-clinic patients 3 (1.6%) had mutations (2 had been treated with azithromycin and was WT before treatment) Doxycyclin is the drug of choice for NGU/cervicitis in Sweden 415 M genitalium pos Danish patients (from GP and STD clinic) 162 (39%) had mutation Azithromycin 1g x1 is the drug of choice for NGU/cervicitis in Denmark 30 M genitalium strains from Greenlandic patients 30 (100%) had mutation Azithromycin 1g x1 is the drug of choice for NGU/cervicitis in Greenland C. trachomatis insidence >5,500 pr

20 Summary Increasing macrolide resistance Single dose azithromycin probably select resistance gene High bacterial load seems to increase the resistance gene selection First cases of moxifloxacin resistance observed

21 Tidsskriftet 7/2011 Reduser bruken av azitromycin som engangsdose Harald Moi, Didrik F. Vestrheim, Anne Olaug Olsen. Doksycyklin 100 mg x 2 i en uke for klamydia