Treatment of Neisseria gonorrhoeae in the Era of Multidrug Resistance

Ji Yun C Chae; Mi Mi Oh

doi:10.14777/kjutii.2015.10.1.12

Journal List > Korean J Urogenit Tract Infect Inflamm > v.10(1) > 1059904

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Chae and Oh: Treatment of Neisseria gonorrhoeae in the Era of Multidrug Resistance

Review

Korean J Urogenit Tract Infect Inflamm 2015;10(1):12-18.

Published online: 17 April 2015

DOI: https://doi.org/10.14777/kjutii.2015.10.1.12

Treatment of Neisseria gonorrhoeae in the Era of Multidrug Resistance

Ji Yun C Chae, Mi Mi Oh

Department of Urology, Korea University College of Medicine, Seoul, Korea

Correspondence to: Mi Mi Oh, http://orcid.org/0000-0002-1232-2598, Department of Urology, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 152-703, Korea Tel: +82-2-2626-3203, Fax: +82-2-2626-1321 E-mail: mamah@hanmail.net

Received 28 February 2014 Revised 18 March 2014 Accepted 25 March 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Neisseria gonorrhoeae (NG) is becoming increasingly less susceptible to the extended spectrum cephalosporin (ESC), which has been recommended for first-line treatment, and cases of treatment failure are being reported globally. An era of untreatable gonorrhea may have started, and it calls for novel treatment strategies. Essential actions should include use of higher doses of ceftriaxone administered as part of dual therapy and further development of alternative drug combinations. This review focuses on the global spread of ESC resistant NG and potential treatment options for the future.

Keywords: Neisseria gonorrhoeae, Drug resistance, Cephalosporins

REFERENCES

1. Marrazzo JM, Handsfield H, Sparling F. Neisseria gonorrhoeae. Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 7th ed.Philadelphia: Elsevier;2010.

2. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999; 75:3–17.

3. World Health Organization. Global incidence and prevalence of selectable curable sexually transmitted infections: 2008. Geneva, Switzerland: WHO. 2012.

4. Unemo M, Shafer WM. Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution, and lessons learned for the future. Ann N Y Acad Sci. 2011; 1230:E19–28.

5. Yokoi S, Deguchi T, Ozawa T, Yasuda M, Ito S, Kubota Y, et al. Threat to cefixime treatment for gonorrhea. Emerg Infect Dis. 2007; 13:1275–7.

6. Lo JY, Ho KM, Leung AO, Tiu FS, Tsang GK, Lo AC, et al. Ceftibuten resistance and treatment failure of Neisseria gonorrhoeae infection. Antimicrob Agents Chemother. 2008; 52:3564–7.

7. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Anti-microb Agents Chemother. 2012; 56:1273–80.

8. Allen VG, Mitterni L, Seah C, Rebbapragada A, Martin IE, Lee C, et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA. 2013; 309:163–70.

9. Lewis DA. Global resistance of Neisseria gonorrhoeae: when theory becomes reality. Curr Opin Infect Dis. 2014; 27:62–7.

10. Lewis DA. The Gonococcus fights back: is this time a knock out? Sex Transm Infect. 2010; 86:415–21.

11. Deguchi T, Yasuda M, Yokoi S, Ishida K, Ito M, Ishihara S, et al. Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval. J Infect Chemother. 2003; 9:35–9.

12. Ito M, Yasuda M, Yokoi S, Ito S, Takahashi Y, Ishihara S, et al. Remarkable increase in central Japan in 2001-2002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones. Anti-microb Agents Chemother. 2004; 48:3185–7.

13. Barry PM, Klausner JD. The use of cephalosporins for gonorrhea: the impending problem of resistance. Expert Opin Pharmacother. 2009; 10:555–77.

14. Bolan GA, Sparling PF, Wasserheit JN. The emerging threat of untreatable gonococcal infection. N Engl J Med. 2012; 366:485–7.

15. Centers for Disease Control and Prevention (CDC). Cephalosporin susceptibility among Neisseria gonorrhoeae isolates–United States, 2000-2010. MMWR Morb Mortal Wkly Rep. 2011; 60:873–7.

16. Chisholm SA, Alexander S, Desouza-Thomas L, Maclure-Webster E, Anderson J, Nichols T, et al. GRASP Collaborative Group. Emergence of a Neisseria gonorrhoeae clone showing decreased susceptibility to cefixime in England and Wales. J Antimicrob Chemother. 2011; 66:2509–12.

17. Cole MJ, Unemo M, Hoffmann S, Chisholm SA, Ison CA, van de Laar MJ. The European gonococcal antimicrobial surveillance programme, 2009. Euro Surveill. 2011; 16.

18. Golparian D, Hellmark B, Fredlund H, Unemo M. Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden. Sex Transm Infect. 2010; 86:454–60.

19. Kirkcaldy RD, Ballard RC, Dowell D. Gonococcal resistance: are cephalosporins next? Curr Infect Dis Rep. 2011; 13:196–204.

20. Kubanova A, Frigo N, Kubanov A, Sidorenko S, Lesnaya I, Polevshikova S, et al. The Russian gonococcal antimicrobial susceptibility programme (RU-GASP)–national resistance prevalence in 2007 and 2008, and trends during 2005-2008. Euro Surveill. 2010; 15.

21. European Centre for Disease Prevention and Control. Gonococcal antimicrobial susceptibility surveillance in Europe– 2010. London, United Kingdom: European Centre for Disease Prevention and Control. 2012.

22. Cámara J, Serra J, Ayats J, Bastida T, Carnicer-Pont D, Andreu A, et al. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother. 2012; 67:1858–60.

23. Tapsall JW, Ndowa F, Lewis DA, Unemo M. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther. 2009; 7:821–34.

24. Pandori M, Barry PM, Wu A, Ren A, Whittington WL, Liska S, et al. Mosaic penicillin-binding protein 2 in Neisseria gonorrhoeae isolates collected in 2008 in San Francisco, California. Anti-microb Agents Chemother. 2009; 53:4032–4.

25. Unemo M, Golparian D, Potočnik M, Jeverica S. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill. 2012; 17.

26. Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother. 2011; 55:3538–45.

27. Shimuta K, Unemo M, Nakayama S, Morita-Ishihara T, Dorin M, Kawahata T, et al. Antibiotic-Resistant Gonorrhea Study Group. Antimicrobial resistance and molecular typing of Neisseria gonorrhoeae isolates in Kyoto and Osaka, Japan, 2010 to 2012: intensified surveillance after identification of the first strain (H041) with high-level ceftriaxone resistance. Antimicrob Agents Chemother. 2013; 57:5225–32.

28. Centers for Disease Control and Prevention (CDC). Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012; 61:590–4.

29. Workowski KA, Berman S. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59:1–110.

30. Choi SM, Hwang JY. Update to Sexually Transmitted Infection Korean Treatment Guidelines. Cheongju: Korea Centers for Disease Control and Prevention. 2013.

31. Ison CA, Town K, Obi C, Chisholm S, Hughes G, Livermore DM, et al. GRASP collaborative group. Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis. 2013; 13:762–8.

32. Tapsall JW. Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci. Sex Transm Infect. 2009; 85:256–8.

33. Bignell C. IUSTI/WHO. 2009 European (IUSTI/WHO) guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2009; 20:453–7.

34. Unemo M, Shipitsyna E, Domeika M. Eastern European Sexual and Reproductive Health (EE SRH) Network Antimicrobial Resistance Group. Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial. Sex Transm Infect. 2010; 86:442–4.

35. Takahashi S, Kurimura Y, Hashimoto J, Uehara T, Hiyama Y, Iwasawa A, et al. Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan. J Infect Chemother. 2013; 19:50–6.

36. Muratani T, Inatomi H, Ando Y, Kawai S, Akasaka S, Matsumoto T. Single dose 1 g ceftriaxone for urogenital and pharyngeal infection caused by Neisseria gonorrhoeae. Int J Urol. 2008; 15:837–42.

37. Newman LM, Moran JS, Workowski KA. Update on the management of gonorrhea in adults in the United States. Clin Infect Dis. 2007; 44(Suppl 3):S84–101.

38. Bignell C, Fitzgerald M. Guideline Development Group; British Association for Sexual Health and HIV UK. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS. 2011; 22:541–7.

39. Furuya R, Nakayama H, Kanayama A, Saika T, Iyoda T, Tatewaki M, et al. In vitro synergistic effects of double combinations of beta-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae. J Infect Chemother. 2006; 12:172–6.

40. Chisholm SA, Dave J, Ison CA. High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. Antimicrob Agents Chemother. 2010; 54:3812–6.

41. Starnino S, Stefanelli P. Neisseria gonorrhoeae Italian Study Group. Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy. J Antimicrob Chemother. 2009; 63:1200–4.

42. Katz AR, Komeya AY, Soge OO, Kiaha MI, Lee MV, Wasserman GM, et al. Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States. Clin Infect Dis. 2012; 54:841–3.

43. Barbee LA, Dombrowski JC. Control of Neisseria gonorrhoeae in the era of evolving antimicrobial resistance. Infect Dis Clin North Am. 2013; 27:723–37.

44. Boslego JW, Tramont EC, Takafuji ET, Diniega BM, Mitchell BS, Small JW, et al. Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae. N Engl J Med. 1987; 317:272–8.

45. Unemo M, Golparian D, Skogen V, Olsen AO, Moi H, Syversen G, et al. Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism (mutated ribosomal protein S5) verified in Norway. Antimicrob Agents Chemother. 2013; 57:1057–61.

46. Chisholm SA, Quaye N, Cole MJ, Fredlund H, Hoffmann S, Jensen JS, et al. An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in Europe. J Antimicrob Chemother. 2011; 66:592–5.

47. Dowell D, Kirkcaldy RD. Effectiveness of gentamicin for gonorrhoea treatment: systematic review and metaanalysis. Postgrad Med J. 2013; 89:142–7.

48. Ross JD, Lewis DA. Cephalosporin resistant Neisseria gonorrhoeae: time to consider gentamicin? Sex Transm Infect. 2012; 88:6–8.

49. Bignell C, Garley J. Azithromycin in the treatment of infection with Neisseria gonorrhoeae. Sex Transm Infect. 2010; 86:422–6.

50. Unemo M, Golparian D, Limnios A, Whiley D, Ohnishi M, Lahra MM, et al. In vitro activity of ertapenem versus ceftriaxone against Neisseria gonorrhoeae isolates with highly diverse ceftriaxone MIC values and effects of ceftriaxone resistance determinants: ertapenem for treatment of gonorrhea? Anti-microb Agents Chemother. 2012; 56:3603–9.

51. Unemo M, Nicholas RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012; 7:1401–22.

52. Golparian D, Fernandes P, Ohnishi M, Jensen JS, Unemo M. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains, including those with high-level antimicrobial resistance: potential treatment option for gonorrhea? Antimicrob Agents Chemother. 2012; 56:2739–42.

53. Llano-Sotelo B, Dunkle J, Klepacki D, Zhang W, Fernandes P, Cate JH, et al. Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob Agents Chemother. 2010; 54:4961–70.

Table 1.

Revised regimens of treatment in gonococcal infection

Classification	Recommended regimens	Alternative regimens
Uncomplicated gonococcal infections of the cervix, urethra and rectum	Ceftriaxone 250 mg IM in a single dose+azithromycin 1 g PO in a single dose or Ceftriaxone 250 mg IM in a single dose+doxycycline 100 mg PO twice a day for 7 days	In case that Ceftriaxone cannot be used - Spectinomycin 2 g IM in a single dose or - Cefixime 400 mg PO in a single dose + azithromycin 1 g PO in a single dose (in 1 week) or - Cefixime 400 mg PO in a single dose + Doxycycline 100 mg PO twice a day for 7 days (in 1 week)
		In case of showing allergy to cephalosporins - Spectinomycin 2 g IM in a single dose or - Azithromycin 2 g PO in a single dose (in 1 week)
Uncomplicated gonococcal infections of the pharynx	Ceftriaxone 250 mg IM in a single dose+azithromycin 1 g PO in a single dose or Ceftriaxone 250 mg IM in a single dose+doxycycline 100 mg PO twice a day for 7 days	In case that Ceftriaxone cannot be used - Cefixime 400 mg PO in a single dose+azithromycin 1 g PO in a single dose (in 1 week) or - Cefixime 400 mg PO in a single dose +doxycycline 100 mg PO twice a day for 7 days (in 1 week) In case of showing allergy to cephalosporins - Azithromycin 2 g PO in a single dose (in 1 week)

IM: intramuscular, PO: per os. Ceftriaxone (Hoffmann-La Roche, Basel, Switzerland).

TOOLS

Similar articles