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Reviews

New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae

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Pages 243-256 | Received 04 Nov 2015, Accepted 16 Dec 2015, Published online: 03 Feb 2016

References

Papers of special note have been highlighted as:

• of interest

•• of considerable interest

  • Elias J, Frosch M, Vogel U. Neisseria. Jorgensen JH, Pfaller MA, et al., editors. Manual of clinical microbiology. 11th ed. Washington (DC):American Society for Microbiology Press; 2015. p.635–21.
  • Chacko MR, Wiemann CM, Smith PB. Chlamydia and gonorrhea screening in asymptomatic young women. J Pediatr Adolesc Gynecol. 2004;17:169–178.
  • Wiesenfeld HC, Hillier SL, Krohn MA, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol. 2002;100:456–463.
  • Holmes KK, Counts GW, Beaty HN. Disseminated gonococcal infection. Ann Intern Med. 1971;74:979–993.
  • Belkacem A, Caumes E, Ouanich J, et al. Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009-2011. Sex Transm Infect. 2013;89:613–615.
  • World Health Organization (WHO). Global incidence and prevalence of selected curable sexually transmitted infections - 2008. Geneva: World Health Organization; 2012. p. 2012.
  • Svensson L, Weström L, Ripa KT, et al. Differences in some clinical and laboratory parameters in acute salpingitis related to culture and serologic findings. Am J Obstet Gynecol. 1980;138:1017–1021.
  • Westrom LV. Sexually transmitted diseases and infertility. Sex Transm Dis. 1994;21:532–537.
  • Westrom L. Effects of acute pelvic inflammatory disease on infertility. Am J Obstetrics Gynecol. 1975;121:707.
  • Ndowa F, Lusti-Narasimhan M. The threat of untreatable gonorrhoea: implications and consequences for reproductive and sexual morbidity. Reprod Health Matters. 2012;20:76–82.
  • Ebrahim SH, McKenna MT, Marks JS. Sexual behaviour: related adverse health burden in the United States. Sex Transm Infect. 2005;81:38–40.
  • Murray CJ, Barber RM, Foreman KJ, et al. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition. Lanet. 2015;386:2145–2191.
  • Owusu-Edusei K Jr, Chesson HW, Gift TL, et al. The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sex Transm Dis. 2013;40:197–201.
  • Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention (CDC); 2013 [cited 2015 Oct 29]. Available from: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.
  • Epstein E. Failure of penicillin in treatment of acute gonorrhea in American troops in Korea. J Am Med Assoc. 1959;169:1055–1059.
  • Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014;27:587–613.

•• One of the most extensive reviews about antimicrobial resistance in Neisseria gonorrhoeae

  • Bignell C, Unemo M. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2013;24:85–92.
  • Australasian Sexual Health Alliance (ASHA). Australian STI management guidelines for use in primary care. [cited 2015 Oct 29]. Available from: www.sti.guidelines.org.au/sexually-transmissible-infections/gonorrhoea#management.
  • Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR–03):1–137.
  • Public Health Agency of Canada. Canadian guidelines on sexually transmitted infections. Gonococcal Infections Chapter; 2013 cited 2015 Oct 29]. Available from: www.phac-aspc.gc.ca/std-mts/sti-its/cgsti-ldcits/assets/pdf/section-5-6-eng.pdf.
  • 日本性感染症学会. 2011 年度版発行に際して. [cited 2015 Oct 29]. Available from: http://jssti.umin.jp/pdf/guideline-2011.pdf.
  • World Health Organization. Guidelines for the management of sexually transmitted diseases. World Health Organization; 2003. ISBN: 92 4 154626 3. Available from: http://www.who.int/hiv/pub/sti/en/STIGuidelines2003.pdf.
  • Trebach JD, Chaulk CP, Page KR, et al. Neisseria gonorrhoeae and Chlamydia trachomatis among women reporting extragenital exposures. Sex Transm Dis. 2015;42:233–239.
  • Wong HT, Lee KC, Chan DP. Community-based sexually transmitted infection screening and increased detection of pharyngeal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae infections in female sex workers in Hong Kong. Sex Transm Dis. 2015;42:185–191.
  • Wada K, Uehara S, Mitsuhata R, et al. Prevalence of pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae among heterosexual men in Japan. J Infect Chemother. 2012;18:729–733.
  • Barbee LA, Khosropour CM, Dombrowski JC, et al. An estimate of the proportion of symptomatic gonococcal, chlamydial and non-gonococcal non-chlamydial urethritis attributable to oral sex among men who have sex with men: a case-control study. Sex Transm Infect. 2015 Aug 21;pii: sextrans-2015–052214. doi:10.1136/sextrans-2015-052214. [Epub ahead of print].
  • World Health Organization (WHO), Department of Reproductive Health and Research. Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva (Switzerland): WHO; 2012. p. 1–36.
  • Unemo M. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect Dis. 2015;15:364.
  • Ohnishi M, Golparian D, Shimuta 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;55:3538–3545.
  • Unemo M, Golparian D, Nicholas R, et al. High-level cefixime- and ceftriaxone-resistant N. gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012;56:1273–1280.
  • Cámara J, Serra J, Ayats J, et al. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother. 2012;67:1858–1860.
  • Tapsall J, Read P, Carmody C, et al. Two cases of failed ceftriaxone treatment in pharyngeal gonorrhoea verified by molecular microbiological methods. J Med Microbiol. 2009;58:683–687.
  • Chisholm SA, Mouton JW, Lewis DA, et al. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J Antimicrob Chemother. 2010;65:2141–2148.

•• Even though this article is analyzed based on old parameters, the pharmacodynamics for clinical treatment failure was well described.

  • Chen YM, Stevens K, Tideman R, et al. Failure of 500 mg of ceftriaxone to eradicate pharyngeal gonorrhoea, Australia. J Antimicrob Chemother. 2013;68:1445–1447.
  • Golparian D, Ohlsson A, Janson H, et al. Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 2014. Euro Surveill. 2014;31(30):19.
  • Waugh MA. Open study of the safety and efficacy of a single oral dose of azithromycin for the treatment of uncomplicated gonorrhoea in men and women. J Antimicrob Chemother. 1993;31(Suppl E):193–198.
  • Handsfield HH, Dalu DA, Martin DH, et al. Multicenter trial of single-dose azithromycin vs. ceftriaxone in the treatment of uncomplicated gonorrhea. Sex Transm Dis. 1994;21:107–111.
  • Young H, Palmer HM. Gonococcal antibiotic surveillance in Scotland (GASS): prevalence, pattern and trends in 2005. HPS Wkly. 2006;40:54–55.
  • Bignell C, Garley J. Azithromycin in the treatment of infection with Neisseria gonorrhoeae. Sex Trans Infect. 2010;86:422–426.
  • Yasuda M, Ito S, Kido A, et al. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis. J Antimicrob Chemother. 2014;69:3116–3118.

• Describes the recent clinical results of 2 g azithromycin treatment according to azithromycin minimum inhibitory concentrations

  • Roberts MC, Chung WO, Roe D, et al. Erythromycin-resistant Neisseria gonorrhoeae and oral commensal Neisseria spp. carry known rRNA methylase genes. Antimicrob Agents Chemother. 1999;43:1367–1372.
  • Ng LK, Martin I, Liu G, et al. Mutation in 23S rRNA associated with macrolide resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2002;46:3020–3025.
  • 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;54:3812–3816.
  • Morita-Ishihara T, Unemo M, Furubayashi K, et al. Treatment failure with 2 g of azithromycin (extended-release formulation) in gonorrhoea in Japan caused by the international multidrug-resistant ST1407 strain of Neisseria gonorrhoeae. J Antimicrob Chemother. 2014;69:2086–2090.
  • Palmer HM, Young H, Winter A, et al. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother. 2008;62:490–494.
  • Starnino S, Stefanelli P. Neisseria gonorrhoeae Italian Study Group I. Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy. J Antimicrob Chemother. 2009;63:1200–1204.
  • Katz AR, Komeya AY, Soge OO, 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;54:841–843.
  • Unemo M, Golparian D, Hellmark B. First three Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Sweden: a threat to currently available dual-antimicrobial regimens for treatment of gonorrhea? Antimicrob Agents Chemother. 2013;58:624–625.
  • Stevens K, Zaia A, Tawil S, et al. Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Australia. J Antimicrob Chemother. 2015;70:1267–1268.
  • Xue J, Ni C, Zhou H, et al. Occurrence of high-level azithromycin-resistant Neisseria gonorrhoeae isolates in China. J Antimicrob Chemother. 2015 Aug 27;70:3404–3405.
  • Lynagh Y, Mac Aogáin M, Walsh A, et al. Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland. J Antimicrob Chemother. 2015;70:2411–2413.
  • Galimand M, Gerbaud G, Courvalin P. Spectinomycin resistance in Neisseria spp. due to mutations in 16S rRNA. Antimicrob Agents Chemother. 2000;44:1365–1366.
  • Unemo M, Fasth O, Fredlund H, et al. Phenotypic and genetic characterization of the 2008WHONeisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J Antimicrob Chemother. 2009;63:1142–1151.
  • Unemo M, Golparian D, Skogen V, 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;57:1057–1061.
  • Ison CA, Littleton K, Shannon KP, et al. Spectinomycin resistant gonococci. Br Med J (Clin Res Ed). 1983;287:1827–1829.
  • Easmon CS, Forster GE, Walker GD, et al. Spectinomycin as initial treatment for gonorrhoea. Br Med J. 1984;289:1032–1034.
  • Boslego JW, Tramont EC, Takafuji ET, et al. Effect of spectinomycin use on the prevalence of spectinomycin-resistant and penicillinase-producing Neisseria gonorrhoeae. N Engl J Med. 1987;317:272–278.
  • Lee H, Hong SG, Soe Y, et al. Trends in antimicrobial resistance of Neisseria gonorrhoeae isolated from Korean patients from 2000 to 2006. Sex Transm Dis. 2011;38:1082–1086.
  • Lee H, Unemo M, Kim HJ, et al. Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea. J Antimicrob Chemother. 2015;70:2536–2542.

• Demonstrates the maintained activity of spectinomycin even though it is a nationwide long-term treatment

  • Moran JS. Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important? Sex Transm Dis. 1995;22:39–47.
  • Barbee LA, Dombrowski JC, Kerani R, et al. Effect of nucleic acid amplification testing on detection of extragenital gonorrhea and chlamydial infections in men who have sex with men sexually transmitted disease clinic patients. Sex Transm Dis. 2014;41:168–172.
  • Walsh A, Rourke FO, Crowley B. Molecular detection and confirmation of Neisseria gonorrhoeae in urogenital and extragenital specimens using the Abbott CT/NG Real Time assay and an in-house assay targeting the porA pseudogene. Eur J Clin Microbiol Infect Dis. 2011;30:561–567.
  • Felarca AB, Laqui EM, Ibarra LM. Gentamicin in gonococcal urethritis of Filipino males: dosage and response. J Infect Dis. 1971;124(Suppl):S287–292.
  • Tan NJ, Rajan VS, Pang R, et al. Gentamicin in the treatment of infections due to penicillinase-producing gonococci. Br J Vener Dis. 1980;56:394–396.
  • Hira SK, Attili VR, Kamanga J, et al. Efficacy of gentamicin and kanamycin in the treatment of uncomplicated gonococcal urethritis in Zambia. Sex Transm Dis. 1985;12:52–54.
  • Olsen B, Lan PT, Golparian D, et al. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011. BMC Infect Dis. 2013;13:40.
  • Olsen B, Månsson F, Camara C, et al. Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa: a prospective cohort study. BMJ Open. 2012;2:e000636.
  • Chisholm SA, Quaye N, Cole MJ, et al. An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in Europe. J Antimicrob Chemother. 2011;66:592–595.
  • Daly CC, Hoffman I, Hobbs M, et al. Development of an antimicrobial susceptibility surveillance system for Neisseria gonorrhoeae in Malawi: comparison of methods. J Clin Microbiol. 1997;35:2985–2988.
  • Brown LB, Krysiak R, Kamanga G, et al. Neisseria gonorrhoeae antimicrobial susceptibility in Lilongwe, Malawi, 2007. Sex Transm Dis. 2010;37:169–172.
  • Dowell D, Kirkcaldy RD. Effectiveness of gentamicin for gonorrhoea treatment: systematic review and meta-analysis. Sex Transm Infect. 2012;88:589–594.
  • Hathorn E, Dhasmana D, Duley L, et al. The effectiveness of gentamicin in the treatment of Neisseria gonorrhoeae: a systematic review. Syst Rev. 2014;3:104.
  • Rodríguez A, Gallego A, Olay T, et al. Bacteriological evaluation of fosfomycin in clinical studies. Chemotherapy. 1977;23(Suppl 1):247–258.
  • Dickgiesser N, Kuntz P. The activity of rosoxacin, fosfomycin, cefotiam, and spectinomycin on beta-lactamase producing Neisseria gonorrhoeae. Br J Vener Dis. 1984;60:154–156.
  • Hauser C, Hirzberger L, Unemo M, et al. In vitro activity of fosfomycin alone and in combination with ceftriaxone or azithromycin against clinical Neisseria gonorrhoeae isolates. Antimicrob Agents Chemother. 2015;59:1605–1611.
  • Unemo M, Golparian D, Limnios A, 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? Antimicrob Agents Chemother. 2012;56:3603–3609.
  • Quaye N, Cole MJ, Ison CA. Evaluation of the activity of ertapenem against gonococcal isolates exhibiting a range of susceptibilities to cefixime. J Antimicrob Chemother. 2014;69:1568–1571.
  • Deshpande LM, Gales AC, Jones RN. GAR-936 (9-t-butylglycylamido-minocycline) susceptibility test development for streptococci, Haemophilus influenzae and Neisseria gonorrhoeae: preliminary guidelines and interpretive criteria. Int J Antimicrob Agents. 2001;18:29–35.
  • Falagas ME, Karageorgopoulos DE, Dimopoulos G. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of tigecycline. Curr Drug Metab. 2009;10:13–21.
  • Nix DE, Matthias KR. Should tigecyclinebe considered for urinary tract infections? A pharmacokinetic re-evaluation. J Antimicrob Chemother. 2010;65:1311–1312.
  • Sato K, Hoshino K, Tanaka M, et al. Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates. Antimicrob Agents Chemother. 1992;36:1491–1498.
  • Hamasuna R, Yasuda M, Ishikawa K, et al. The second nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan, 2012-2013. J Infect Chemother. 2015;21:340–345.
  • Tanaka M, Nakayama H, Haraoka M, et al. Susceptibilities of Neisseria gonorrhoeae isolates containing amino acid substitutions in GyrA, with or without substitutions in ParC, to newer fluoroquinolones and other antibiotics. Antimicrob Agents Chemother. 2000;44:192–195.
  • Nakashima M, Uematsu T, Kosuge K, et al. Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers. Antimicrob Agents Chemother. 1995;39:170–174.
  • Matsumoto T, Uchino K, Yamaguchi H, et al. Study on the safety and efficacy of sitafloxacin–results of the use-results survey. Jpn J Antibiot. 2011;64:319–337. Japanese
  • Furuya R, Nakayama H, Kanayama A, et al. In vitro synergistic effects of double combinations of beta-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae. J Infect Chemother. 2006;12:172–176.
  • Furuya R, Koga Y, Irie S, et al. In vitro activities of antimicrobial combinations against clinical isolates of Neisseria gonorrhoeae. J Infect Chemother. 2013;19:1218–1220.
  • Pereira R, Cole MJ, Ison CA. Combination therapy for gonorrhoea: in vitro synergy testing. J Antimicrob Chemother. 2013;68:640–643.
  • Barbee LA, Soge OO, Holmes KK, et al. In vitro synergy testing of novel antimicrobial combination therapies against Neisseria gonorrhoeae. J Antimicrob Chemother. 2014;69:1572–1578.
  • Wind CM, De Vries HJC, Van Dam AP. Determination of in vitro synergy for dual antimicrobial therapy against resistant Neisseria gonorrhoeae using Etest and agar dilution. Int J Antimicrob Agents. 2015;45:305–308.

•• Demonstrates the effect of 65 combinations using Etest and agar dilution and also requirement for standardization of testing methods

  • Pettus K, Sharpe S, Papp JR. In vitro assessment of dual drug combinations to inhibit growth of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2015;59:2443–2445.
  • Kirkcaldy RD, Weinstock HS, Moore PC, et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis. 2014;59:1083–1091.

•• Demonstrates the clinical result of two combinations in vivo

  • Putnam SD, Castanheira M, Moet GJ, et al. CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria. Diagn Microbiol Infect Dis. 2010;66:393–401.
  • Mallegol J, Fernandes P, Seah C, et al. Determination of in vitro activity of solithromycin at different pHs and its intracellular activity tested against clinical isolates of Neisseria gonorrhoeae from a laboratory collection. Antimicrob Agents Chemother. 2013;57:4322–4328.
  • Golparian D, Fernandes P, Ohnishi M, et al. In vitro activity of the new fluoroketolidesolithromycin (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;56:2739–2742.
  • Hook EW 3rd, Golden M, Jamieson BD, et al. A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea. Clin Infect Dis. 2015;61:1043–1048.
  • Jacobsson S, Golparian D, Alm RA, et al. High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea. Antimicrob Agents Chemother. 2014;58:5585–5588.
  • Huband MD, Bradford PA, Otterson LG, et al. In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA gyrase/topoisomerase inhibitor with potent activity against Gram-positive, fastidious Gram-Negative, and atypical bacteria. Antimicrob Agents Chemother. 2015;59:467–474.
  • Unemo M, Ringlander J, Wiggins C, et al. High In Vitro Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014. Antimicrob Agents Chemother. 2015;59:5220–5225.

•• The first report of phase 2 clinical trial for solithromycin under development

  • Jerse AE, Deal CD. Vaccine research for gonococcal infections: where are we? Sex Transm Infect. 2013;89(Suppl 4):iv63–8.
  • Craig AP, Gray RT, Edwards JL, et al. The potential impact of vaccination on the prevalence of gonorrhea. Vaccine. 2015;33:4520–4525.

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