The emergence of Neisseria gonorrhoeae strains that are resistant to azithromycin and extended-spectrum cephalosporins represents a public health threat, that of untreatable gonorrhea infections. Multivariate regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to the overall antimicrobial MICs for ceftriaxone, cefixime, azithromycin, tetracycline, ciprofloxacin, and penicillin. A training data set consisting of 1,280 N. gonorrhoeae strains was used to generate regression equations which were then applied to validation data sets of Canadian (n = 1,095) and international (n = 431) strains. The predicted MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) were fully explained by 5 amino acid substitutions in PenA, A311V, A501P/T/V, N513Y, A517G, and G543S; the presence of a disrupted mtrR promoter; and the PorB G120 and PonA L421P mutations. The correlation of predicted MICs within one doubling dilution to phenotypically determined MICs of the Canadian validation data set was 95.0% for ceftriaxone, 95.6% for cefixime, 91.4% for azithromycin, 98.2% for tetracycline, 90.4% for ciprofloxacin, and 92.3% for penicillin, with an overall sensitivity of 99.9% and specificity of 97.1%. The correlations of predicted MIC values to the phenotypically determined MICs were similar to those from phenotype MIC-only comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics to better monitor the dynamics of N. gonorrhoeae.

In Canada, N. gonorrhoeae isolates with decreased susceptibilities to third-generation cephalosporins have increased over the years. The alterations in penA, mtrR, and porB1b (penB alteration) are important determinants identified in these isolates. The most common STs identified among these Canadian isolates have also been reported worldwide.

Background Neisseria gonorrhoeae have acquired resistance to many antimicrobials, including third generation cephalosporins and azithromycin, which are the current gonococcal combination therapy recommended by the Canadian Guidelines on Sexually Transmitted Infections . Objective To describe antimicrobial susceptibilities for N. gonorrhoeae circulating in Canada between 2012 and 2016. Methods Antimicrobial resistance profiles were determined using agar dilution of N. gonorrhoeae isolated in Canada 2012–2016 (n=10,167) following Clinical Laboratory Standards Institute guidelines. Data were analyzed by applying multidrug-resistant gonococci (MDR-GC) and extensively drug-resistant gonococci (XDR-GC) definitions. Results Between 2012 and 2016, the proportion of MDR-GC increased from 6.2% to 8.9% and a total of 19 cases of XDR-GC were identified in Canada (0.1%, 19/18,768). The proportion of isolates with decreased susceptibility to cephalosporins declined between 2012 and 2016 from 5.9% to 2.0% while azithromycin resistance increased from 0.8% to 7.2% in the same period. Conclusion While XDR-GC are currently rare in Canada, MDR-GC have increased over the last five years. Azithromycin resistance in N. gonorrhoeae is established and spreading in Canada, exceeding the 5% level at which the World Health Organization states an antimicrobial should be reviewed as an appropriate treatment. Continued surveillance of antimicrobial susceptibilities of N. gonorrhoeae is necessary to inform treatment guidelines and mitigate the impact of resistant gonorrhea.

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.

Background: Gonorrhea is on the rise in Canada. Treatment has been complicated by the fact that Neisseria gonorrhoeae has acquired resistance to many antibiotics, including penicillin, tetracycline, erythromycin and ciprofloxacin. The emergence of isolates with decreased susceptibilities to the third generation cephalosporins and reports of treatment failures in Canada and around the world are cause for concern.Objective: To assess the resistance levels of common antibiotics to N. gonorrhoeae and to observe trends in resistance and/or decreased susceptibility to ciprofloxacin, third generation cephalosporins and azithromycin.Methods: Laboratory surveillance data for N. gonorrhoeae isolates submitted by provincial microbiology laboratories to the National Microbiology Laboratory (NML) from 2009-2013 were compared. Results:Since 2009, there has been an overall rise in antibiotic-resistant N. gonorrhoeae. In 2013, 24.3% of the isolates were resistant to erythromycin, 18.9% were resistant to penicillin, 33.0% were resistant to tetracycline, and 29.3% were resistant to ciprofloxacin. The percentage of isolates with decreased susceptibility to ceftriaxone (≥0.125 mg/L) and/or cefixime (≥0.25 mg/L) was 3.9% in 2013. This number represents a decrease from 5.9% in 2012 and 7.6% in 2011. The proportion of azithromycin resistant (MIC ≥2 mg/L) N. gonorrhoeae isolates increased from 0.4% in 2009 to 1.2% in 2013. Conclusion:Resistance to erythromycin, penicillin, tetracycline and ciprofloxacin is common. Decreased susceptibility to ceftriaxone and/or cefixime is now almost 4% and azithromycin resistance is emerging but remains low at 1.2%. These results have informed the gonococcal infection treatment recommendations in the Canadian Guidelines on Sexually Transmitted Infections. Pen MIC ≥ 2.0 mg/L, Tet MIC ≥ 2.0 mg/L but ≤ 8.0 mg/L and Ery MIC ≥ 2.0 mg/L Probable CMRNG Probable Chromosomal Mediated Resistant N. gonorrhoeae One of the MIC values of Pen, Tet, Ery = 1 mg/L, the other two ≥ 2.0 mg/L TetR Tetracycline Resistant N. gonorrhoeae (chromosomal mediated) Tet MIC ≥ 2.0 mg/L but ≤ 8.0 mg/L CipR Ciprofloxacin Resistant N. gonorrhoeae Cip MIC ≥ 1.0 mg/L AzR Azithromycin Resistant N. gonorrhoeae Az MIC ≥ 2.0 mg/L SpecR Spectinomycin Resistant N. gonorrhoeae Spec R ≥ 128 mg/L CxDS N. gonorrhoeae with decreased susceptibility to Ceftriaxone Cx MIC ≥ 0.125 mg/L CeDS N. gonorrhoeae with decreased susceptibility to Cefixime Ce MIC ≥ 0.25 mg/L