In its evolution over the past century, Neisseria gonorrhoeae (the causative agent of gonorrhea infection) has successively acquired resistance to first-line treatments, including penicillin, doxycycline, and ciprofloxacin. Recent international surveillance data suggest that with time the bacterium may become fully resistant to the current (and only remaining viable) third-generation cephalosporin treatments (cefixime PO and ceftriaxone IM). In this context, local surveillance for signs of emerging resistance is critical.
Methods: The BC Public Health Microbiology and Reference Laboratory (PHMRL) routinely tests N. gonorrhoeae isolates for susceptibility to a panel of antimicrobial drugs, including cefixime, ceftriaxone, and azithromycin. We measured the minimum inhibitory concentration (MIC) of these drugs among isolates from BC and examined patterns over time and by site of infection. The MIC represents the lowest amount of drug required to inhibit growth of the bacterium; a higher MIC thus suggests that the bacterium is less susceptible to the drug.
Findings: A total of 1837 isolates were tested between 2006 and 2011, representing 22% of all gonorrhea cases reported in the province. While no isolate was fully resistant to cefixime or ceftriaxone* and no treatment failures were reported in BC during this period, 1% of isolates showed MIC just below the non-susceptible threshold for cefixime. Furthermore, the percentage of isolates with cefixime or ceftriaxone MIC within three dilutions of the non-susceptible threshold (also termed “elevated MIC”) increased over the past 6 years. Likewise, the percentage of isolates non-susceptible to azithromycin** or within two dilutions of this threshold increased over time.
* MIC breakpoints to define “resistance” to cefixime and ceftriaxone have not yet been established; however, the Clinical and Laboratory Standards Institute defines MIC ≤0.25 μg/mL as susceptible. ** The US CDC has proposed MIC ≥2 μg/mL as the non-susceptible threshold for azithromycin.
Fifty-one percent of isolates tested for drug susceptibility were sampled from the urethra, 23% from the rectum (99% of which were from male clients), 13% from the cervix, and 12% from the throat (91% from males). Susceptibility to all drugs showed a consistent pattern by site of infection whereby rates of elevated MIC (reduced susceptibility) were highest at the rectal site, next highest at the throat, lower in urethral specimens, and lowest in cervical specimens.
Implications: The trend toward rising MIC—or decreased susceptibility—for first-line gonococcal treatments in BC is mirrored in data from other parts of the world and suggests that full resistance to these drugs may eventually develop. The threat of cefixime and ceftriaxone resistance has focused attention on several STI prevention and control measures, including increased testing, adjustments in treatment guidelines, thorough partner notification for gonorrhea cases, and tests of cure. Ceftriaxone 250mg IM is now the preferred treatment for gonorrhea in Canada, particularly for pharyngeal infections and for men who have sex with men (a recommendation substantiated by above data from BC). Cefixime (PO) is still available as an alternative for patients who do not want an injection; however, the recommended dose is increased to 800mg. All cases of gonorrhea should be co-treated with azithromycin 1g PO, to both address high rates of chlamydial co-infection and help stem the further emergence of drug resistance by using multiple classes of drugs.
Acknowledgements: Linda Hoang, Miguel Imperial (BC PHMRL Bacteriology Laboratory); Mark Gilbert, Rich Lester, Gina Ogilvie (BCCDC Clinical Prevention Services); Rachel McKay, David Patrick (BCCDC Antibiotic Resistance Program)