Research in action: Dr. Vanessa Allen
Her research on drug-resistant gonorrhea
PHO microbiologist Dr. Vanessa Allen
knew there was a significant problem with gonorrhea; the second most commonly reported sexually transmitted infection in Ontario and North America. For years she had noted gonorrhea’s resistance to its last prescribed form of treatment. “Case reports of clinical failure in Japan and Europe and emerging patterns of resistance identified in the laboratories was concerning,” says Allen. “Cefixime, the pill form of the cephalosporin-class drug, and the last class of antibiotic effective against gonorrhoea, was under threat.”
Antimicrobial resistance in Neisseria gonorrhoeae (N. gonorrhoeae), the causative agent of gonorrhea, had been a concern since penicillin was initially introduced in the 1940s. Left untreated, gonorrhea can lead to a host of complications including pelvic inflammatory disease, infertility and disseminated infection. Since then, Allen says, the successive loss of efficacy of previously used antimicrobials, including sulfa-based compounds, penicillin, tetracyclines, spectinomycin, and the fluoroquinolones for the treatment of gonorrhea means the cephalosporins are the last commercially available treatment option recommended for treatment.
At PHO’s STI laboratories, Allen and her colleagues conducted a first-of-its-kind study in collaboration with Hassle Free Clinic in Toronto and the National Microbiology Laboratory in Winnipeg. They evaluated the clinical efficacy of cefixime for the treatment of gonorrhea in light of elevated resistance identified in the PHO labs. They used a retrospective cohort study of culture positive N. gonorrhoeae infections at a single sexual health clinic (Hassle Free Clinic in Toronto) that routinely performs test-of-cure. The cohort comprised N. gonorrhoeae culture positive individuals identified between May 1, 2010 and April 30, 2011 treated with cefixime as recommended by Public Health Agency of Canada (PHAC) guidelines.
Their findings confirmed what Allen and others suspected: that clinical failure following treatment with cefixime was relatively high, at close to seven per cent of those in the study group. Furthermore, of the 133 isolates, 28 had decreased susceptibility in the laboratory.
Why is this significant, too? It suggests that clinical failures are occurring among strains that were thought to be susceptible to antibiotics, and further implies that the issue of cefixime-resistant gonorrhea is probably more significant than suggested previously by national and international organizations such as PHAC, the US Centers for Disease Control (CDC), and the World Health Organization. The study results, along with Allen’s previous findings at the PHO laboratories, suggest that the ongoing use of cefixime should be re-evaluated.
The Journal of the American Medical Association published the findings in January 2013. Most notably, this study presented the first series of clinical failures of gonorrhea associated with the use of cefixime in North America, identified by the concurrent strategies of routine test-of-cure and culture based testing for N. gonorrhoeae. The full study, “Neisseria gonorrhoeae Treatment Failure and Susceptibility to Cefixime in Toronto, Canada” by Allen VG, Mitterni L, Seah C, Rebbapragada A, Martin IE, Lee C, Siebert H, Towns L, Melano RG, Low DE is available at: http://jama.jamanetwork.com/article.aspx?articleid=1556149
In addition to media, there has been considerable North American public health interest in these findings. Allen has been invited to contribute to a re-evaluation of clinical breakpoints for the cephalosporins in the treatment of N. gonorrhoeae by the US-led Clinical Laboratories Standards Institute, and has had opportunities for ongoing exchange with PHAC and the CDC to address this important problem of cephalosporin-resistant gonorrhea.
Based on Allen’s work, she and colleagues at PHO, in collaboration with the Ministry of Health and Long-Term Care, have developed new clinical guidelines for the management of gonorrhea in Ontario, to be released in April 2013. Similar to guidelines produced by the CDC, these guidelines will advise clinicians to treat the infection with an intramuscular injection as well as an oral pill. They are similar to guidelines developed by the CDC. “My hope is that one day we can prevent the ongoing transmission of this infection, and any further development of drug resistance. But until then, our goal is provide the right diagnostic tools for clinicians and the most effective treatment for patients,” says Allen.