Ontario researchers call for better awareness of treatment guidelines for gonorrhea

CATIE News

Want to receive publications straight to your inbox?

CATIE

The bacteria that cause the sexually transmitted infection (STI) gonorrhea have been developing resistance to potent antibiotics since the mid-20th century when these drugs began to be used as a treatment for this infection. In the past decade, gonorrhea’s resistance to treatment seems to have accelerated. During that time, Canadian recommendations for first-line treatment of gonorrhea (in the Canadian Guidelines on Sexually Transmitted Infections) have had to change several times. Furthermore, in 2013, the Ontario Ministry of Health released its own publication: Guidelines for the Testing and Treatment of Gonorrhea.

Receive CATIE News in your inbox:

When it comes to first-line treatment of uncomplicated gonorrhea, both sets of guidelines are in alignment—a combination of antibiotics. Where the guidelines differ is in the type of combination therapy preferred for first-line use, as follows:

  • The Canadian guidelines offer a choice of combination pill therapy (cefixime 800 mg and azithromycin 1 g) or a combination of an intramuscular injection of ceftriaxone 250 mg and oral azithromycin 1 g. For gay, bisexual and other men who have sex with men, ceftriaxone and azithromycin is the preferred regimen.
  • The Ontario guidelines prefer the combination of intramuscular ceftriaxone and oral azithromycin for everyone (in the same doses as the Canadian guidelines) because of trends of decreasing susceptibility of gonorrhea to cefixime in that province.

Other high-income countries, such as Australia, the UK and the U.S., also recommend a combination of intramuscular ceftriaxone and azithromycin therapy for gonorrhea.

Changing adherence to guidelines

Researchers at the University of Ottawa have been reviewing data on the treatment prescribed to people with gonorrhea in Ontario. The researchers found that from 2006 to about mid-2014 (the length of the study) adherence to the Canadian guidelines and updates to the guidelines varied. Initially, after the Canadian guidelines were periodically updated, adherence to them was low but gradually rose as awareness and knowledge about the updates diffused among care providers. However, despite the update to the Canadian STI guidelines in 2011 and the province of Ontario issuing its own guidelines in 2013, the research team found that 40% of people with gonorrhea were not receiving guideline-recommended care in May 2014. The researchers assert that this puts those patients “at risk of treatment failure and potentially promoting further drug resistance.”

The study authors suggested ways to enhance the dissemination of updated STI guidelines in the future. These are mentioned later in this bulletin.

Study details

Researchers analysed data collected from Ontario’s Integrated Public Health Information System (iPHIS). This database is used by public health units across the province to send information about reportable infections to the Ontario Ministry of Health. The data reviewed focused on the prescription of antibiotics for gonorrhea between January 1, 2006 and May 31, 2017.

Results

Researchers were able to review data from 32,272 cases of gonorrhea.

In the first several years of the study, adherence to the Canadian STI guidelines was very high, with about 90% of cases receiving the recommended first-line therapy. In 2011, the information on gonorrhea treatment was updated in the Canadian guidelines and researchers found that shortly after the update was issued adherence to the guidelines fell significantly. Although adherence gradually increased, it never rose to levels seen in the beginning of the study.

Overall, according to the researchers, “adherence to first-line treatment recommendations for gonorrhea in Ontario decreased following guideline changes; these effects were greater following major changes in recommendations.”

What to do?

The researchers said that for future updates of the guidelines certain dissemination strategies could be used to help educate clinicians, including the following:

  • “educational outreach”
  • “working with opinion leaders”
  • “electronic reminders”
  • “auditing and feedback [about prescribing patterns] tailored to address barriers faced by clinicians”

The researchers noted that such strategies have been effective at “promoting changes in practice” in other fields of medicine.

The tide of resistance

In 2011 gonorrhea treatment guidelines in Canada (and in the other high-income countries previously mentioned) recommended a switch from single-agent therapy to combination therapy. This change in treatment likely significantly slowed or even decreased the development of gonorrhea with reduced susceptibility to ceftriaxone. However, Canadian researchers have found a worrying trend: Strains of gonorrhea with resistance to azithromycin have been on the increase since 2011.

In 2014 in the UK there was a report of a case of treatment failure with standard doses of ceftriaxone and azithromycin. In Japan, strains of gonorrhea with reduced susceptibility to ceftriaxone are increasing. And in some other countries, strains of gonorrhea with resistance to azithromycin have been reported. In this context, the World Health Organization has predicted that untreatable multidrug-resistant strains of gonorrhea may arise in the future. Although there are some promising experimental antibiotics in development that could be used to treat gonorrhea, there are no currently licensed ideal alternatives to the combination of ceftriaxone and azithromycin.

—Sean R. Hosein

Resources

Gonorrhea – CATIE/SIECCAN fact sheet

Canadian Guidelines on Sexually Transmitted Infections

Treatment of N. gonorrhoeae in response to the discontinuation of spectinomycin: Alternative treatment guidance statement from Canadian Guidelines on Sexually Transmitted Infections

Ontario Guidelines for the Testing and Treatment of Gonorrhea

British Columbia Treatment Guidelines: Sexually Transmitted Infections in Adolescents and Adults

Alberta treatment guidelines for sexually transmitted infections (STI) in adolescents and adults 2012

Infection non compliquée à chlamydia trachomatis ou à neisseria gonorrhoeae – INESS

REFERENCES:

  1. Dickson C, Taljaard M, Friedman DS, et al. The antibiotic management of gonorrhoea in Ontario, Canada following multiple changes in guidelines: an interrupted time-series analysis. Sexually Transmitted Infections. 2017; in press.
  2. Johnson AP, Hughes G. The prospect of untreatable gonorrhoea. BMJ. 2017 Aug 25;358:j3973.
  3. Martin I, Sawatzky P, Liu G, et al. Decline in decreased cephalosporin susceptibility and increase in azithromycin resistance in Neisseria gonorrhoeae, Canada. Emerging Infectious Diseases. 2016 Jan;22(1):65-7.
  4. Hottes TS, Lester RT, Hoang LM, et al. Cephalosporin and azithromycin susceptibility in Neisseria gonorrhoeae isolates by site of infection, British Columbia, 2006 to 2011. Sexually Transmitted Diseases. 2013 Jan;40(1):46-51.
  5. Unemo M, Golparian D, Nicholas R, et al. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrobial Agents and Chemotherapy. 2012 Mar;56(3):1273-80.
  6. Abrams AJ, Kirkcaldy RD, Pettus K, et al. A case of decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae in the absence of a mosaic penicillin-binding protein 2 (penA) allele. Sexually Transmitted Diseases. 2017 Aug;44(8):492-494.
  7. Iwata A, Shimuta K, Ohnishi M. Conjunctivitis caused by a strain of Neisseria gonorrhoeae that was less susceptible to ceftriaxone. Internal Medicine. 2017;56(11):1443-1445.
  8. Town K, Obi C, Quaye N, et al. Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales. Sexually Transmitted Infections. 2017 Feb;93(1):39-45.
  9. Fifer H, Natarajan U, Jones L, et al. Failure of dual antimicrobial therapy in treatment of gonorrhea. New England Journal of Medicine. 2016 Jun 23;374(25):2504-6.
  10. Gianecini R, Oviedo C, Stafforini G, et al. Neisseria gonorrhoeae resistant to ceftriaxone and cefixime, Argentina. Emerging Infectious Diseases. 2016 Jun;22(6):1139-41.
  11. Chisholm SA, Wilson J, Alexander S, et al. An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England. Sexually Transmitted Infections. 2016 Aug;92(5):365-7.
  12. European Centres for Disease Prevention and Control. Gonorrhoea strains across Europe becoming more susceptible to main treatment options. ECDC News. 29 August 2017. Available at: https://ecdc.europa.eu/en/news-events/gonorrhoea-strains-across-europe-becoming-more-susceptible-main-treatment-options