National Surveillance of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Annual Summary 2013

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Table of Contents

Figures and Tables

Acknowledgements

Authorship and Lead Contributors:

Streptococcus and STI Unit
Bacteriology and Enteric Diseases Program
National Microbiology Laboratory
Public Health Agency of Canada
Pam Sawatzky, Gary Liu, Irene Martin (Unit Head)
Dr. Michael Mulvey (Chief, Antimicrobial Resistance and Nosocomial Infections)

Other Contributors:

Surveillance and Epidemiology Division
Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada
Dr. Chris Archibald, Margaret Bodie, Stephanie Totten, Ming Su

Professional Guidelines and Public Health Practice Division
Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada
Dr. Tom Wong, Dr. Margaret Gale-Rowe, Dr. Jun Wu, Lisa Pogany

This report has been reviewed by Canadian Public Health Laboratory Network (CPHLN) Provincial and Territorial Laboratory Directors.

The results presented in this report represent Neisseria gonorrhoeae isolates kindly submitted from the following hospitals or provincial public health laboratories:

British Columbia Centre for Disease Control, Vancouver, British Columbia:
Dr. Judy Isaac-Renton, Dr. Linda Hoang, Ana Paccagnella

Provincial Laboratory of Public Health Alberta, Edmonton, Alberta:
Dr. Graham Tipples, Dr. Greg Tyrrell

Saskatchewan Disease Control Laboratory, Regina, Saskatchewan:
Dr. Greg Horsman, Rosanne Kitzul

Cadham Provincial Laboratory, Winnipeg, Manitoba:
Dr. Paul Van Caessele, Sandra Giercke, Denise Sitter

Public Health Laboratories, Public Health Ontario, Etobicoke, Ontario:
Dr. Frances Jamieson, Dr. Vanessa Allen, Lynn Towns, Dayle Noda

Laboratoire de santé publique du Québec, Ste-Anne-de-Bellevue, Québec:
Dr. Cecile Tremblay, Dr. Brigitte Lefebvre

Queen Elizabeth II Health Science Centre, Halifax, Nova Scotia
Dr. David Haldane

New Brunswick Regional Hospitals:
Dr. Lewis Abbott, Dr. Richard Garceau

Newfoundland Public Health Laboratory, St. John's, Newfoundland:
Dr. Sam Ratnam, Laura Gilbert

Neisseria gonorrhoeae cultures were not reported to the NML or received from the Northwest Territories, Nunavut or the Yukon.

Executive Summary

  • This report compares laboratory surveillance data for Neisseria gonorrhoeae isolates submitted by provincial microbiology laboratories to the National Microbiology Laboratory (NML) from 2009-2013.
  • The Canadian reported rate of gonorrhoea is on the rise and has more than doubled from 14.9 per 100,000 in 1997 to 36.2 per 100,000 in 2012. Gonorrhoea is the second most commonly reported bacterial sexually transmitted infection in Canada with 12,561 cases reported in 2012.
  • Over time, N. gonorrhoeae has acquired resistance to many antibiotics such as penicillin, tetracycline, erythromycin and ciprofloxacin. Antimicrobial resistance in N. gonorrhoeae is  a serious threat to effective treatment of gonococcal infections.
  • In 2013, a total of 3,195 N. gonorrhoeae isolates were cultured in public health laboratories across Canada; 1,183 of these were submitted to the NML for antimicrobial susceptibility testing. The total number of isolates cultured in all provinces was used as the denominator to calculate resistance proportion.
  • In Canada, the increasing minimum inhibitory concentrations (MICs) to the 3rd generation cephalosporins are of concern. Modal MICs to cefixime increased from 0.032 mg/L in 2008 to 0.125 mg/L in 2010 but then decreased to 0.063 mg/L in 2013. Modal MICs to ceftriaxone increased from 0.032 mg/L in 2008 to 0.063 mg/L from 2009 to 2013.
  • Using the WHO breakpoints of decreased susceptibility to cefixime at MIC≥0.25 mg/L and decreased susceptibility to ceftriaxone at MIC≥0.125 mg/L (WHO, 2012), the percentage of isolates with decreased susceptibility to ceftriaxone and/or cefixime was 3.9% (124/3,195) in 2013. This number represents a decrease from 5.9% (179/3,036) in 2012 and 7.6% (254/3,360) in 2011.
  • Isolates with decreased susceptibility to cefixime have declined from a high of 4.2% (140/3,360) in 2011 to 1.8% (56/3,195) in 2013. Isolates with decreased susceptibility to ceftriaxone have declined from a high of 7.3% (218/2,970) in 2010 to 3.5% (112/3,195) in 2013.
  • The proportion of azithromycin resistant (MIC ≥2 mg/L) N. gonorrhoeae isolates increased from 0.4% (11/3,106) in 2009 to 1.2% (37/3,195) in 2013.
  • The proportion of ciprofloxacin resistant N. gonorrhoeae increased from 1.3% (59/4,458) in 2000 to a high of 36.0% (1,068/2,970) in 2010, subsequently decreasing to 29.3% (937/3,195) in 2013.
  • In 2013, 24.3% (777/3,195) of the isolates were resistant to erythromycin; 18.9% (605/3,195) were resistant to penicillin; 33.0% (1054/3,195) were resistant to tetracycline.
  • The NML began testing ertapenem and gentamicin in 2012. In 2012, the modal MIC for ertapenem was 0.063 mg/L which increased to 0.125 mg/L in 2013. The gentamicin modal MIC was 8 mg/L in 2012 and 2013.
  • Since 2010, all N. gonorrhoeae isolates submitted to the NML were also analyzed by molecular genotyping using the N. gonorrhoeae multi-antigen sequence type (NG-MAST) method. In 2013, 294 different sequence types (STs) were identified among the 1,183 isolates tested and the most common sequence types were ST-2400, ST-9663 and ST-5985 at 12.1%, 7.4% and 6.1%, respectively.

Introduction

Neisseria gonorrhoeae is the causative agent of gonorrhoea and is the second most commonly reported bacterial sexually transmitted infection in Canada, with 12,561 cases reported in 2012 (Public Health Agency of Canada, 2014). Rates of reported cases of gonorrhoea have more than doubled from 14.9 cases per 100,000 population in 1997 to 36.2 cases per 100,000 population in 2012  (Public Health Agency of Canada, 2014). Globally, gonorrhoea is a public health threat with an estimated 106 million cases each year (World Health Organization, 2012). In 2012 the World Health Organization released a global action plan to control the spread and impact of antimicrobial resistance in N. gonorrhoeae (World Health Organization, 2012) and the CDC reported drug resistant N. gonorrhoeae at an urgent hazard level, requiring serious public health attention (Centres for Disease Control and Prevention, 2013). The treatment and control of gonorrhoea is complicated by the ability of N. gonorrhoeae to evolve and develop resistance to many of the antibiotics used to treat it, including penicillins, tetracyclines, macrolides and quinolones (Barry, 2009; Tapsall, 2006). The emergence of isolates with decreased susceptibilities to the cephalosporins (Golparin, 2010; Ison, 2011; Pandori, 2009; Tapsall, 2008; World Health Organization, 2011) and reports of treatment failures in Canada (Allen, 2013) and around the world raises the possibility of gonorrhea infections becoming untreatable in the future. Azithromycin resistant isolates have also been identified. The emergence of high-level azithromycin resistant (≥256 mg/L) N. gonorrhoeae has been reported internationally (Chisholm, 2009) and isolates with this high level azithromycin resistance have now been identified in Canada. In response to the increasing MICs and reports of cefixime treatment failures, the Canadian Sexually Transmitted Infection (STI) Guidelines regarding gonorrhoea treatment have been updated to a combination therapy with 250 mg ceftriaxone intramuscularly and azithromycin 1 g orally as a first-line treatment for uncomplicated anogenital and pharyngeal infection in adults. Additional information on the treatment of gonococcal infection is available at http://www.phac-aspc.gc.ca/std-mts/sti-its/cgsti-ldcits/assets/pdf/section-5-6-eng.pdf.

A further challenge to the laboratories monitoring antimicrobial susceptibilities of gonorrhoea is that the number of cultures available for antimicrobial susceptibility testing is on the decline due to the shift from the use of culture to Nucleic Acid Amplification Test (NAAT) for the diagnosis of gonorrhoea (Figure 1). This is of concern as N. gonorrhoeae cultures are required for antimicrobial susceptibility testing and some jurisdictions in Canada no longer maintain the capacity to culture this organism. In fact, over 70% of gonococcal infections in Canada are now diagnosed using NAAT and therefore antimicrobial susceptibility data in these jurisdictions are not available.

To make improvements to the current surveillance program, the enhanced surveillance of antimicrobial resistant N. gonorrhoeae (ESAG) study will begin in 2014. This sentinel public health practice and surveillance study for N. gonorrhoeae will collect integrated practice, epidemiological and laboratory information. The objectives of the study are to determine the trends and characteristics of antimicrobial resistance in N. gonorrhoeae, antimicrobial useand the treatment failure rate associated with regimens recommended by the Canadian STI Guidelines. Both antimicrobial susceptible and resistant strains of gonorrhoea will be characterized in order to understand the pattern of spread of strains in various populations in Canada and to inform Canadian guidance on STI management.

The National Microbiology Laboratory (NML), in collaboration with the provincial laboratories, has been monitoring the antimicrobial susceptibilities of N. gonorrhoeae since 1985; these results inform the gonococcal infection treatment recommendations in the Canadian Guidelines on Sexually Transmitted Infections.

Methods

In 2013, provincial public health laboratories submitted a total of 1,183 viable N. gonorrhoeae isolates to the NML for antimicrobial susceptibility testing as part of the passive National Neisseria gonorrhoeae Surveillance Program (Table 1).These data are provided to indicate the overall submission rate for resistance testing from the different provinces across Canada and the overall percentage of isolates resistant to at least one antibiotic. In addition to the isolates, information on age and gender of the patient and anatomical site of infection were also submitted to the NML (Tables 4 and 5).

N. gonorrhoeae isolates are submitted to the NML when the provincial laboratories identify resistance to at least one antibiotic or if the provincial laboratories do not perform any antimicrobial susceptibility testing. Submission of isolates is voluntary and is not standardized across the country. The overall interpretation of the results is difficult due to the limitations related to the isolates available for testing. Therefore, the total number of isolates cultured in all provinces was used as the denominator to calculate resistance proportion. To standardize the susceptibility testing between laboratories, proficiency surveys were conducted semi-annually. Minimum inhibitory concentration, or MIC (the minimum concentration of antibiotic which will inhibit the growth of the organism) was performed using agar dilution, and interpretations were based on the criteria outlined in Table 2.  Resistance characterization definitions are provided in Table 3. Isolates were also characterized by plasmid profiles analysis, production of β-lactamase and the presence of tetM determinant.

N. gonorrhoeae isolates were also analyzed by molecular genotyping using the N. gonorrhoeae multi-antigen sequence type (NG-MAST) method (Martin, 2004) that incorporates the amplification of the porin gene (por) and the transferrin-binding protein gene (tbpB). DNA sequences of both strands were edited, assembled and compared using DNAStar, Inc. software. The resulting sequences were submitted to the NG-MAST website (http://www.ng-mast.net/) to determine the sequence types (ST).

Table 1. Number of Neisseria gonorrhoeae Culture Isolates Tested at the NML by Province, 2009-2013Footnote aFootnote b
Province 2009 2010 2011 2012 2013 Total
Footnote a

Total number of isolates tested by the provincial laboratories is used as the denominator in all % resistance calculations.

Return to footnote a referrer

Number of cases reported and percentage of total cases tested in 2013 are estimated.

Return to footnote b referrer

British Columbia 183 256 176 92 170 877
Alberta 91 164 156 94 136 641
Saskatchewan 30 11 35 57 67 200
Manitoba 3 11 12 8 7 41
Ontario 383 383 428 403 498 2,095
Québec 216 335 282 390 301 1,524
New Brunswick 4 9 6 3 5 27
Nova Scotia 2 69 77 0 1 149
Newfoundland 2 7 0 0 1 10
Prince Edward Island 0 0 0 1 2 3
Total isolates received at NML 914 1,245 1,172 1,048 1,188 5,567
Total viable isolates available for testing 913 1,233 1,158 1,031 1,183 5,518
Total isolates resistant to at least one antibiotic 873 1,137 1,075 987 1,153 5,225
Total number of isolates tested in each provinceFootnote a 3,106 2,970 3,360 3,036 3,195 15,667
Percentage of isolates resistant to at least one antibiotic 28.1% 38.3% 32.0% 32.5% 36.1% 33.4%
Percentage of total cases tested 27.8% 26.1% 29.5% 24.2% 26.6%Footnote b 26.8%
Total cases reported in Canada 11,178 11,397 11,394 12,561 12,000Footnote b 58,530
Table 2. Neisseria gonorrhoeae Antimicrobial Resistance CriteriaFootnote aFootnote b
Antibiotic Recommended Testing Concentration Ranges (mg/L) MIC Interpretive Standard (mg/L)Footnote a Sources of Antibiotics
S DS I R
Footnote a

MIC Interpretative standards as recommended by the Clinical and Laboratory Standards Institute (CLSI, 2014) except for erythromycin (Ehret, 1996) and azithromycin (Centres for Disease Control and Prevention, 2007) and ceftriaxone and cefixime (World Health Organization, 2012).

Return to footnote a referrer

Footnote b

S = Susceptible, I = Intermediate, R = Resistant, DS = Decreased susceptibility

Return to footnote b referrer

Penicillin 0.032 - 128.0 ≤ 0.06   0.12- 1.0 ≥ 2.0 Sigma #P 7794
Tetracycline 0.064 - 64.0 ≤ 0.25   0.5 - 1.0 ≥ 2.0 Sigma #T 3383
Erythromycin 0.032 - 32.0 ≤1.0     ≥ 2.0 Sigma #E 5389
Spectinomycin 4.0 - 256.0 ≤ 32.0   64 ≥ 128.0 Sigma #S 9007
Ciprofloxacin 0.001 - 64.0 ≤ 0.06   0.12 - 0.5 ≥ 1.0 Bayer Health Care
Ceftriaxone 0.001 - 2.0 ≤ 0.25 ≥ 0.125     Sigma #C 5793
Cefixime 0.002 - 2.0 ≤ 0.25 ≥ 0.25     Wyeth - Ayerst
Azithromycin 0.016 - 32.0 ≤ 1.0     ≥ 2.0 Pfizer
Ertapenem 0.002 - 2.0 Interpretive Standards Not Available Sequoia SRP01333e
Gentamicin 0.5 - 128 Interpretive Standards Not Available MP Biomedicals

Table 3. Neisseria gonorrhoeae Antimicrobial Resistance Characterization Definitions
Characterization Description Definition
PPNG Penicillinase Producing Neisseria gonorrhoeae Pen MIC ≥ 2.0 mg/L, β-lactamase positive, β-lactamase plasmid (3.05, 3.2 or 4.5 Mdal plasmid)
TRNG Tetracycline Resistant Neisseria gonorrhoeae Tet MIC ≥ 16.0 mg/L, 25.2 Mdal plasmid, TetM PCR positive
CMRNG Chromosomal Mediated Resistant Neisseria gonorrhoeae 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 Neisseria gonorrhoeae One of the MIC values of Pen, Tet, Ery = 1 mg/L, the other two ≥ 2.0 mg/L
PenR Penicillin Resistant Neisseria gonorrhoeae Pen MIC ≥ 2.0 mg/L, β-lactamase negative
TetR Tetracycline Resistant Neisseria gonorrhoeae Tet MIC ≥ 2.0 mg/L but ≤ 8.0 mg/L
EryR Erythromycin Resistant Neisseria gonorrhoeae Ery MIC ≥ 2.0 mg/L
CipR Ciprofloxacin Resistant Neisseria gonorrhoeae Cip MIC ≥ 1.0 mg/L
AzR Azithromycin Resistant Neisseria gonorrhoeae Az MIC ≥ 2.0 mg/L
SpecR Spectinomycin Resistant Neisseria gonorrhoeae Spec R ≥ 128 mg/L
CxDS Neisseria gonorrhoeae with Decreased Susceptiblity  to Ceftriaxone Cx MIC ≥ 0.125 mg/L
CeDS Neisseria gonorrhoeae with Decreased Susceptiblity  to Cefixime Ce MIC ≥ 0.25 mg/L

Results and Discussion

In 2013, a total of 3,195 N. gonorrhoeae isolates were cultured in public health laboratories across Canada; 1,183 of these were submitted to the NML and found viable for antimicrobial susceptibility testing. A total of 1,153 were found to be resistant to at least one antibiotic tested; this translates to 36.1% of all N. gonorrhoeae cases diagnosed by culture as carrying antimicrobial resistance (1,153/3,195) (Figure 1). The characterization of each resistant N. gonorrhoeae isolate is provided in Appendix B. Of all the gonorrhoea cases reported in 2013 (approximated at over 12,000 cases), over 70% were diagnosed by NAAT for which there is no antimicrobial susceptibility data.

Gender and age data was available for 99.5% (1,177/1,183) of isolates tested at the NML (Table 4). Of these, 83.1% (978/1,177) were males ranging from 1 month to 74 years of age. A total of 16.9% (199/1,177) of isolates were from females aging 2 to 71 years.

Anatomic source data was available for 74.5% (881/1,183) of the isolates sent to the NML (Table 5). Of these, 56.4% (497/881) were urethral, 21.1% (186/881) were rectal, 9.8% (86/881) were from the throat, 6.8% (60/881) were cervical, 4.1% (36/881) were vaginal and 1.8% (16/881) were from other sources.

Table 4. Demographic Data for the Neisseria gonorrhoeae isolates tested at the NML, 2013 (N=1,183)
Age Male Female Not Specified Totals
Under 15 3 8 0 11
15 - 20 89 53 0 142
21 - 25 224 50 2 276
26 - 35 383 50 1 434
36 - 45 143 21 0 164
46 - 55 99 12 0 111
56 - 65 29 4 0 33
65 + 8 1 0 9
Not Specified 0 0 3 3
Total 978 199 6 1,183
Table 5. Anatomic Isolation Sites for the Neisseria gonorrhoeae isolates tested at the NML, 2013 (N=1,183)
Isolation Site Male Female Not Specified Totals
Penis/Urethra 497 0 0 497
Rectum 180 4 2 186
Throat 71 14 1 86
Cervix 0 60 0 60
Vagina 0 36 0 36
Other 11 5 0 16
Not Specified 219 80 3 302
Total 978 199 6 1,183

Figure 1. Neisseria gonorrhoeae Isolates in Canada, 2000 to 2013Footnote a

Figure 1

   Neisseria gonorrhoeae Isolates in Canada, 2000 to 2013 - Text Description
Figure 1.  Neisseria gonorrhoeae Isolates in Canada, 2000 to 2013Footnote a
Gonorrhea cases 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Number of gonorrhea cases diagnosed by Nucleic Acid Amplification Testing (NAAT) 1731 2165 2900 4006 5299 5580 7133 7598 8816 8072 8427 8034 9525 8805
Number of gonorrhea cases diagnosed by culture and found susceptible 3366 3491 3539 3532 3216 2714 2729 2880 2978 2233 1832 2284 2049 2042
Number of gonorrhea cases diagnosed by culture and found resistant 1092 1100 926 703 802 905 1472 1395 929 873 1138 1076 987 1153
Total 6189 6756 7365 8241 9317 9199 11334 11873 12723 11178 11397 11394 12561 12000

Stacked column graph showing the number of Neisseria gonorrhoeae isolates in Canada from 2000 to 2013. The horizontal axis represents the year with the total number of cases of gonorrhea reported in brackets. The vertical axis represents the number of cases.

Trends in Antimicrobial Sensitivies

In 2013, 13.5% (432/3,195) of isolates were classified as Chromosomal Mediated Resistant Neisseria gonorrhoeae (CMRNG), while the plasmid-mediated resistant strains occurred at lower rates. Penicillinase Producing Neisseria gonorrhoeae (PPNG) accounted for 4.3% (136/3,195) and Tetracycline Resistant Neisseria gonorrhoeae (TRNG)for 8.8% (281/3,195) of isolates (Figure 2).

Figure 2. Trends of PPNG, TRNG, CMRNG, Probable CMRNG Neisseria gonorrhoeae in Canada from 2009 to 2013Footnote a

Figure 2
   Trends of PPNG, TRNG, CMRNG, Probable CMRNG Neisseria gonorrhoeae in Canada from 2009 to 2013 - Text Description
Figure 2. Trends of PPNG, TRNG, CMRNG, Probable CMRNG Neisseria gonorrhoeae in Canada from 2009 to 2013Footnote a
Characterization Year
2006 2007 2008 2009 2010 2011 2012 2013
PPNG 0.98% 0.51% 0.69% 0.9% 0.71% 0.54% 0.59% 0.88%
TRNG 2.43% 1.21% 1.05% 1.64% 1.72% 2.56% 3.39% 5.48%
PPNG/TRNG 1.07% 0.42% 1.15% 1.54% 1.41% 3.1% 2.70% 3.13%
PPNG/CMRNG 0.12% 0.07% 0.13% 0.09% 0.1% 0.27% 0.40% 0.25%
TRNG/CMRNG 0% 0.05% 0.13% 0.06% 0.07% 0.12% 0.20% 0.19%
CMRNG 12.5% 11.67% 9.8% 15.19% 21.82% 17.68% 15.28% 13.08%
Probable CMRNG 8.19% 7.72% 5.22% 4.67% 7.64% 3.75% 4.61% 6.35%

Line graph showing the percentage of PPNG, TRNG, PPNG/TRNG, PPNG/CMRNG, TRNG/CMRNG, CMRNG and Probable CMRNG each year with the total number of isolates tested nationally as the denominator. The horizontal axis represents the year and the vertical axis represents the percentage. The lines represent each of the characterizations.

Figure 3 shows the trends of antimicrobial susceptibilities of N. gonorrhoeae tested in Canada from 2004 to 2013. In 2004, only 9.3% (373/4,018) of Canadian isolates were found to be erythromycin resistant. This percentage increased to 31.5%, (936/2,970) by 2010 but then decreased to 24.3% (777/3,195) by 2013

Penicillin resistance increased from 6.0% (242/4,018) in 2004, to 25.1% (744/2,970) in 2010 and then decreased to 18.9% (605/3,195) in 2013.

Tetracycline resistance increased from 17.8% (715/4,018) in 2004 to 34.6% (1,028/2,970) in 2010. It decreased to 33.0% (1054/3,195) in 2013. Of the 5,518 viable isolates tested at NML between 2009 and 2013, none showed resistance to spectinomycin.

Figure 3. Trends of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Tested in Canada, 2004-2013Footnote a

Figure 3
   Trends of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Tested in Canada, 2004-2013 - Text Description
Figure 3. Trends of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Tested in Canada, 2004 – 2013Footnote a
Antibiotic Year
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Penicillin Resistance 6.02% 9.42% 17.59% 13.94% 12.8% 18.7% 25.05% 22.2% 20.26% 18.94%
Tetracycline Resistance 17.79% 20.92% 28.59% 22.88% 19.09% 24.7% 34.61 29.4 30.3% 32.99%
Erythromycin Resistance 9.28% 12.54% 20.92% 24.89% 16.7% 21.3% 31.52 26.6 23.12% 24.32%
Ciprofloxacin Resistance 6.25% 15.67% 29.42% 30.2% 21.96% 25.5% 35.93% 29.3% 28.52% 29.33%
Azithromycin Resistance 0.15% 0.22% 0.19% 0.16% 0.13% 0.35% 1.25% 0.39% 0.86% 1.16%
Cefixime Decreased Susceptibility 0.07% 0% 0.07% 0.09% 0.46% 1.19% 3.3% 4.2% 2.24% 1.75%
Ceftriaxone Decreased Susceptibility 0% 0% 0.019% 0.42% 0.6% 3.12% 7.34% 6.2% 5.53% 3.51%

Line graph showing the proportion of  resistant Neisseria gonorrhoeae isolates with each line representing an antibiotic and the number of isolates tested nationally as the denominator. The horizontal axis represents the year and the vertical axis represents the percentage.

Third Generation Cephalosporins

In 2013, according to WHO (2012) definitions (isolates with MICs ≥0.25 mg/L for cefixime and ≥0.125 mg/L for ceftriaxone have decreased susceptibility), 1.8% of isolates (56/3,195) were identified as having decreased susceptibility to cefixime and 3.5% (112/3,195) were identified as having decreased susceptibility to ceftriaxone. These rates are higher than they were in 2008 [0.5% (18/3,907) and 0.6% (24/3,907), respectively] but lower than in 2011 [4.2% (140/3,360) and 6.2% (208/3,360), respectively] (Figure 4).

In 2013, 3.9% of isolates (124/3,195) were identified with decreased susceptibility to ceftriaxone and/or cefixime decreasing from 5.9% in 2012 (179/3,036) and 7.6% in 2011 (254/3,360).

The geographical distribution of N. gonorrhoeae isolates with decreased susceptibility to cefixime and ceftriaxone within Canada are represented in Figures 5 and 6 and in Tables 6 and 7.

Figure 4. Neisseria gonorrhoeae Isolates Received by the NML between 2008 and 2013 with Decreased Susceptibility to Cefixime and CeftriaxoneFootnote a

Figure 4
   Neisseria gonorrhoeae Isolates Received by the NML between 2008 and 2013 with Decreased Susceptibility to Cefixime and Ceftriaxone - Text Description
Figure 4.  Neisseria gonorrhoeae Isolates Received by the NML between 2008 and 2013 with Decreased Susceptibility to Cefixime and CeftriaxoneFootnote a
Dilution (mg/L) Year
2008 2009 2010 2011 2012 2013
Cefixime (≥ 0.25 mg/L) 0.46% 1.19% 3.3% 4.2% 2.24% 1.75%
Ceftriaxone  (≥ 0.125 mg/L) 0.61% 3.12% 7.34% 6.2% 5.53% 3.51%

Line graph demonstrating the proportion of Neisseria gonorrhoeae isolated in Canada with decreased susceptibility to cefixime and ceftriaxone (each antibiotic represented by its own line).  The denominator used is the number of isolates tested nationally.  The horizontal axis represents the year and the vertical axis represents the percentage.

Figure 5. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2009 to 2013Footnote a

Figure 5
   Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2009 to 2013 - Text Description
Figure 5.  Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2009 to 2013Footnote aFootnote b
Province Year
2009 2010 2011 2012 2013
Quebec 0.73% 0.55% 2.20% 0.95% 0.56%
Ontario 0.94% 1.54% 7.18% 3.78% 2.78%
Manitoba 0.00% 0.00% 3.23% 0.00% 0.00%
Alberta 0.26% 3.89% 0.88% 0.80% 0.97%
British Columbia 4.73% 18.71% 4.08% 2.42% 1.54%
Nova Scotia 0.00% 0.00% 6.49% 0.00% 0.00%
Saskatchewan 0.00% 0.00% 0.00% 1.75% 1.45%
Total No. of isolates 35 98 10 68 56
% CeDS of all isolates tested nationallyFootnote b 1.1% 3.3% 4.2% 2.2% 1.8%

A cluster bar graph showing the geographical distribution of Neisseria gonorrhoeae isolates with decreased susceptibility to cefixime (>=0.25 mg/L).  The horizontal axis shows the year, the different colored bars represent the provinces.  The vertical axis represents the percentage.  The denominators used to determine the percentages are the number of cultures tested in each province.

Table 6. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2009 to 2013Footnote a
Province Year
2009 2010 2011 2012 2013
Quebec 7 6 23 8 4
Ontario 13 17 87 46 39
Manitoba 0 0 1 0 0
Alberta 1 11 4 4 5
British Columbia 14 64 20 9 7
Nova Scotia 0 0 5 0 0
Saskatchewan 0 0 0 1 1
Total No. of isolates 35 98 140 68 56
% CeDS of all isolates tested nationally 1.1% 3.3% 4.2% 2.2% 1.8%

Figure 6. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2009 to 2013Footnote a

Figure 6
   Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2009 to 2013 - Text Description
Figure 6. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2009 to 2013Footnote aFootnote b
Province Year
2009 2010 2011 2012 2013
Quebec 2.40% 2.45% 1.72% 4.18% 1.26%
Ontario 2.75% 6.36% 11.14% 8.95% 5.77%
Manitoba 0.00% 0.00% 3.23% 2.04% 3.45%
Alberta 0.52% 6.36% 1.75% 1.61% 1.56%
British Columbia 11.15% 29.82% 8.57% 3.49% 2.86%
Nova Scotia 0.00% 0.00% 5.19% 0.00% 0.00%
Saskatchewan 0.00% 0.00% 0.00% 3.51% 0.00%
Total No. of isolates 96 218 208 168 112
% CxDS of all isolates tested nationallyFootnote b 3.1% 7.3% 6.2% 5.5% 3.5%

A cluster bar graph showing the geographical distribution of Neisseria gonorrhoeae isolates with decreased susceptibility to ceftriaxone (>=0.125 mg/L). The horizontal axis shows the year, the different colored bars represent the provinces. The vertical axis represents the percentage.  The denominators used to determine the percentages are the number of cultures tested in each province.

Table 7. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2009 to 2013Footnote a
Province Year
2009 2010 2011 2012 2013
Quebec 23 27 18 35 9
Ontario 38 70 135 109 81
Manitoba 0 1 1 1 1
Alberta 2 18 8 8 8
British Columbia 33 102 42 13 13
Nova Scotia 0 0 4 0 0
Saskatchewan 0 0 0 2 0
Total No. of isolates 96 218 208 168 112
% CxDS of all isolates tested nationally 3.1% 7.3% 6.2% 5.5% 3.5%

In 2009, 2010 and 2011 the modal MIC for cefixime was 0.125 mg/L decreasing to 0.032 mg/L in 2012 and increasing again to 0.063 in 2013. The ceftriaxone modal MIC has remained at 0.063 mg/L from 2009 thru 2013 (Figures 7-10, Tables 8 and 9).

Figure 7. Trends of Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a

Figure 7
   Trends of Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
Figure 7. Trends of Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Year Dilution (mg/L)
≤0.002 0.004 0.008 0.016 0.032 0.063 0.125 0.25 0.5
2008 (N=947) 0.22% 3.66% 14.84% 25.70% 29.30% 14.20% 1.00% 1.90% 0.11%
2009 (N=913) 0.33% 2.40% 13.33% 22.95% 22.84% 11.15% 23.17% 3.83% 0.00%
2010 (N=1,233) 0.25% 4.66% 9.65% 17.17% 21.59% 10.30% 28.37% 8.01% 0.00%
2011 (N=1,158) 0.35% 2.52% 8.67% 14.48% 18.65% 16.06% 27.20% 12.09% 0.00%
2012 (N=1,031) 0.39% 2.52% 10.94% 17.04% 23.08% 18.23% 21.24% 6.60% 0.00%
2013 (N=1,183) 0.08% 1.61% 14.96% 17.08% 19.36% 26.20% 15.89% 4.31% 0.42%

A clustered bar chart showing the percentage of Neisseria gonorrhoeae with different minimum inhibitory concentrations (MICs) to cefixime for the years specified.  Each year is represented by a different colored bar. The horizontal axis represents the dilution range of the MICs.  The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML.

Figure 8. Trends of Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a

Figure 8
   Trends of Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
Figure 8. Trends of Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Year Dilution (mg/L)
≤0.002 0.004 0.008 0.016 0.032 0.063 0.125 0.25
2009 (N=913) 0.88% 4.16% 10.72% 15.75% 24.62% 33.37% 10.07% 0.44%
2010 (N=1,233) 1.39% 6.80% 8.11% 8.44% 17.38% 40.08% 17.21% 0.57%
2011 (N=1,158) 1.65% 6.42% 7.11% 12.58% 18.99% 35.30% 17.17% 0.78%
2012 (N=1,031) 1.55% 5.42% 10.26% 17.72% 16.94% 31.85% 16.07% 0.19%
2013 (N=1,183) 0.59% 5.66% 14.12% 14.71% 26.54% 28.91% 9.30% 0.17%

A clustered bar chart showing the percentage of Neisseria gonorrhoeae with different minimum inhibitory concentrations (MICs) for ceftriaxone for the years specified. Each year is represented by a different colored bar. The horizontal axis represents the dilution range of the MICs.  The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

Figure 9. Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a

Figure 9
   Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
Figure 9. Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Dilution (mg/L) Year
2009 2010 2011 2012 2013
0.032 mg/L 22.9% 21.5% 18.7% 23.1% 19.4%
0.063 mg/L 11.4% 10.0% 16.1% 18.2% 26.2%
0.125 mg/L 22.9% 28.1% 27.2% 21.2% 15.9%
0.25 mg/L 3.8% 8.0% 12.1% 6.6% 4.3%
0.5 mg/L 0.0% 0.0% 0.0% 0.0% 0.4%
Table 8. Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Dilutions (mg/L) Year
2009 2010 2011 2012 2013
0.032 mg/L 22.9% 21.5% 18.7% 23.1% 19.4%
0.063 mg/L 11.4% 10.0% 16.1% 18.2% 26.2%
0.125 mg/L 22.9% 28.1% 27.2% 21.2% 15.9%
0.25 mg/L 3.8% 8.0% 12.1% 6.6% 4.3%
0.5 mg/L 0.0% 0.0% 0.0% 0.0% 0.4%
Figure 10. Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Figure 10
   Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
Figure 10. Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Dilution (mg/L) Year
2009 2010 2011 2012 2013
0.063 mg/L 33.3% 39.8% 35.3% 31.9% 28.9%
0.125 mg/L 10.1% 17.0% 17.2% 16.1% 9.3%
0.25 mg/L 0.4% 0.6% 0.8% 0.2% 0.2%

Two stacked bar charts, 1 for cefixime and 1 for ceftriaxone. Each whole bar represents a year. Each bar is divided to represent the percentage of isolates with a specific MIC. The horizontal axis shows the year; the vertical axis represents the percentage. The denominator used to determine the percentage is the total number of viable isolates tested by the NML.

Table 9. Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates received by the NML from 2009 to 2013Footnote a
Dilutions (mg/L) Year
2009 2010 2011 2012 2013
0.063 mg/L 33.3% 39.8% 35.3% 31.9% 28.9%
0.125 mg/L 10.1% 17.0% 17.2% 16.1% 9.3%
0.25 mg/L 0.4% 0.6% 0.8% 0.2% 0.2%

Azithromycin

The distribution of azithromycin resistant isolates across Canada is represented in Figure 11 and Table 10.  Azithromycin resistant N. gonorrhoeae increased from 0.4% (11/3,106) in 2009 to 1.2% (37/3,195) in 2013. Between 2009 and 2012, five isolates with high level azithromycin resistance (MIC ≥256 mg/L) were identified in Canada.  The modal MIC for azithromycin has remained at 0.5 mg/L each year between 2009 and 2012.  In 2013, the modal decreased to 0.25 mg/L (Figures 12 and 13 and Table 11). 

In 2012, seven isolates with combined decreased susceptibility to cephalosporins and resistance to azithromycin were identified (0.2%, 7/3,036). In 2013, eight (0.3%, 8/3,195) of these isolates were identified (Table 12). These are the first isolates to emerge in Canada with both decreased susceptibility to cephalosporins and resistance to azithromycin thus threatening the success of currently recommended dual therapy treatment options.

Figure 11. Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013Footnote a

Figure 11
   Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013 - Text Description
Figure 11. Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013Footnote a
Province Year
2009 2010 2011 2012 2013
Quebec 0.21% 1.18% 0.67% 1.67% 1.54%
Ontario 0.00% 0.64% 0.08% 0.74% 0.85%
Alberta 0.00% 5.30% 0.22% 0.20% 0.78%
British Columbia 3.04% 0.58% 0.20% 0.54% 0.88%
Nova Scotia 0.00% 0.00% 1.30% 0.00% 0.00%
Saskatchewan 0.00% 0.00% 16.67% 0.00% 8.70%
Total No. of AzR isolatesFootnote b 11 37 13 26 37
% AzR of all isolates tested nationallyFootnote a 0.4% 1.3% 0.4% 0.9% 1.2%

A cluster bar chart showing the distribution of azithromycin resistant Neisseria gonorrhoeae isolates throughout the provinces from 2009 to 2013. The horizontal axis shows the year, the different colored bars represent the provinces The vertical axis represents the percentage with the denominator being the number of cultures tested in province.

Table 10. Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013Footnote a
Province Year
2009 2010 2011 2012 2013
Quebec 2 13 7 14 11
Ontario 0 7 1 9 12
Alberta 0 15 1 1 4
British Columbia 9 2 1 2 4
Nova Scotia 0 0 1 0 0
Saskatchewan 0 0 2 0 6
Total No. of AzR isolates 11 37 13 26 37
% AzR of all isolates tested nationally 0.4% 1.3% 0.4% 0.9% 1.2%

Figure 12. Trends of Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a

Figure 12
   Trends of Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
12. Trends of Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Year Dilution (mg/L)
0.125 0.25 0.5 1 ≥2
2009 (N=913) 15.00% 24.90% 56.40% 2.40% 1.19%
2010 (N=1,233) 16.06% 18.25% 58.15% 3.57% 2.83%
2011 (N=1,158) 14.25% 23.32% 56.13% 5.18% 1.12%
2012 (N=1,031) 27.74% 24.15% 43.65% 1.84% 2.52%
2013 (N=1,183) 24.26% 36.18% 33.90% 2.54% 3.13%

Clustered bar chart showing the percentage of Neisseria gonorrhoeae within different minimum inhibitory concentrations (MICs) for azithromycin for the years specified. Each year is represented by a different colored bar. The horizontal axis represents the dilution range of the MICs. The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

Figure 13. Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a

Figure 13
   Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013 - Text Description
Figure 13. Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Dilution (mg/L) Year
2009 2010 2011 2012 2013
0.25 mg/L 24.9% 18.3% 23.3% 24.2% 36.2%
0.5 mg/L 56.5% 58.2% 56.1% 43.7% 33.9%
1 mg/L 2.4% 3.6% 5.2% 1.8% 2.5%
≥2 mg/L 1.2% 3.0% 1.1% 2.5% 3.1%

Two bar charts showing distribution of isolates within specific azithromycin MIC dilutions.

A stacked bar chart with whole bar representing a year. Each bar is divided into different colors which represent the percentage of isolates with a specific MIC. The horizontal axis shows the year; the vertical axis represents the percentage. The denominator used to determine the percentage is the total number of viable isolates tested by the NML.

Table 11. Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Received by the NML from 2009 to 2013Footnote a
Dilution (mg/L) Year
2009 2010 2011 2012 2013
0.25 mg/L 24.9% 18.3% 23.3% 24.2% 36.2%
0.5 mg/L 56.5% 58.2% 56.1% 43.7% 33.9%
1 mg/L 2.4% 3.6% 5.2% 1.8% 2.5%
≥2 mg/L 1.2% 3.0% 1.1% 2.5% 3.1%
Table 12. Neisseria gonorrhoeae isolates with combined decreased susceptibility to cephalosporins and resistance to azithromycinFootnote a
Year Number of AziR Isolates Percent AziRFootnote a Number of AziR Isolates with CeDS and/or CxDS Percent AziR Isolates with CeDS and/or CxDS NG-MAST of AziR with CeDS and/or CxDS Provinces
2012 26 0.9% 7 0.2% ST-3158 (6); ST-1407 (1) BC (1), ON (6)
2013 37 1.2% 8 0.3% ST-3158 (6); ST-1407 (1); ST-9427 (1) BC (2), SK (1), ON (5)

Ciprofloxacin

The percentage of ciprofloxacin resistant isolates increased from 1.3% (59/4,458) in 2000 to 29.3% (937/3,195) in 2013. Percentage rates for each province are represented in Figure 13 and Table 13. The modal MIC of ciprofloxacin has shifted dramatically from 0.004 mg/L in 2004 to 16.0 mg/L in 2013 (Figure 15). Of the 937 ciprofloxacin resistant isolates identified in 2013, 94.6% (n=886) were also resistant to at least one other antibiotic; 41.7% (388/937) were characterized as CMRNG.

Figure 14. Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013Footnote a

Figure 14
   Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013 - Text Description
Figure 14. Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoea Isolates, 2009 to 2013Footnote aFootnote b
Province Year
2009 2010 2011 2012 2013
Quebec 21.06% 26.64% 24.59% 41.41% 38.55%
Ontario 24.08% 32.70% 33.09% 29.23% 30.91%
Manitoba 2.94% 41.67% 32.26% 10.20% 13.79%
Alberta 20.63% 49.47% 28.88% 13.08% 16.15%
British Columbia 58.11% 71.05% 33.27% 22.04% 24.23%
Nova Scotia 50.00% 7.25% 22.08% 0.00% 0.00%
New Brunswick 9.09% 55.56% 0.00% 33.33% 60.00%
Saskatchewan 11.11% 25.71% 14.29% 15.79% 36.23%
Newfoundland 0.00% 42.86% 0.00% 0.00% 100.00%
Prince Edward Island 0.00% 0.00% 0.00% 100.00% 50.00%
Total No. of CipR isolates 793 1068 985 866 937
%CipR of all isolates tested nationallyFootnote b 25.5% 36.0% 29.3% 28.5% 29.3%

A cluster bar chart showing the distribution of ciprofloxacin resistant Neisseria gonorrhoeae isolates throughout the provinces from 2009 to 2013. The horizontal axis shows the year, the different colored bars represent the provinces The vertical axis represents the percentage with the denominator being the number of cultures tested in province.

Table 13. Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoeae Isolates, 2009 to 2013Footnote a
Province Year
2009 2010 2011 2012 2013
Quebec 202 293 257 347 276
Ontario 333 360 401 356 434
Manitoba 1 10 10 5 4
Alberta 79 140 132 65 83
British Columbia 172 243 163 82 110
Nova Scotia 1 5 17 0 0
New Brunswick 1 5 0 1 3
Saskatchewan 4 9 5 9 25
Newfoundland 0 3 0 0 1
Prince Edward Island 0 0 0 1 1
Total No. of CipR isolates 793 1068 985 866 937
%CipR of all isolates tested nationally 25.5% 36.0% 29.3% 28.5% 29.3%

Figure 15. Trends in Ciprofloxacin MICs of Neisseria gonorrhoeae Isolates, 2004 to 2013

Figure 15
   Trends in Ciprofloxacin MICs of Neisseria gonorrhoeae Isolates, 2004 to 2013 - Text Description
Figure 15. Trends in Ciprofloxacin MICs of Neisseria gonorrhoeae Isolates, 2004 to 2013
Year Dilution Range (mg/L)
≤0.25 0.5 to 2 4 8 16 ≥32
2004 (N=850) 70.12% 3.53% 10.00% 5.18% 8.71% 2.47%
2005 (N=898) 36.51% 3.45% 7.91% 9.91% 19.27% 22.94%
2006 (N=1,528) 19.04% 2.23% 25.85% 10.86% 31.81% 10.21%
2007 (N=1,432) 9.44% 1.54% 31.35% 15.85% 31.49% 10.34%
2008 (N=947) 9.09% 2.96% 24.82% 13.62% 41.18% 8.44%
2009 (N=913) 12.60% 5.56% 14.70% 17.80% 47.00% 2.52%
2010 (N=1,233) 12.57% 2.92% 14.60% 8.03% 58.64% 3.00%
2011 (N=1,158) 14.68% 12.09% 13.39% 9.84% 46.80% 3.20%
2012 (N=1,031) 15.32% 9.22% 15.91% 16.49% 41.51% 1.55%
2013 (N=1,183) 20.78% 6.00% 21.39% 22.74% 26.71% 2.36%

A clustered bar chart showing the percentage of Neisseria gonorrhoeae within specific minimum inhibitory concentrations (MICs) for ciprofloxacin for the years specified. Each year is represented by a different colored bar. The horizontal axis represents the dilution range of the MICs. The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

Ertapenem and Gentamicin

The NML began testing ertapenem and gentamicin in 2012.  As there are no MIC interpretive standards for N. gonorrhoeae to these 2 antibiotics, only their MIC distribution is presented here. The modal MIC for ertapenem for 2013 was 0.125 mg/L which is 1 log2 dilution higher than the 2012 modal MIC (Figure 16).  However, only 654 out of the 1,031 isolates of 2012 (63.4%) were tested with ertapenem. The gentamicin modal MIC for both 2012 and 2013 is 8 mg/L. There is very little variation in the gentamicin MICs (Figure 17).

Figure 16. Ertapenem MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013Footnote aFootnote b

Figure 16
   Ertapenem MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013 - Text Description
Figure 16. Ertapenem MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013Footnote aFootnote b
Year Dilution Range (mg/L)
0.004 0.008 0.016 0.032 0.063 0.125 0.25 0.5
2013 (N=1175) 0.00% 0.26% 1.45% 13.28% 36.26% 32.43% 15.40% 0.94%
2012 (N=654) 0.15% 0.31% 1.38% 6.42% 24.77% 40.67% 22.94% 3.36%

Clustered bar chart with each year represented by a different colored bar. The horizontal axis represents the dilution range of the MICs. The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

Figure 17. Gentamicin MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013Footnote aFootnote b

Figure 17

Percentages were calculated using the total number of viable strains (both resistant and susceptible isolates) tested by NML as the denominator (N).

   Gentamicin MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013 - Text Description
Figure 17. Gentamicin MICs of Neisseria gonorrhoeae Isolates, 2012 to 2013Footnote aFootnote b
Year Dilution Range (mg/L)
2 4 8 16
2013 (N=1183) 0.08% 4.90% 88.59% 6.42%
2012 (N=721) 0.28% 4.30% 92.37% 3.05%

Clustered bar chart, with each year represented by a different colored bar. The horizontal axis represents the dilution range of the MICs. The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

Neisseria gonorrhoeae Multi-antigen Sequencing (NG-MAST)

NG-MAST molecular-based sequence typing provides a substantial level of discrimination between isolates. In 2013, the most common sequence types (STs) identified by the NML were ST-2400 [12.1% (143/1,183)], ST-9663 [7.4% (87/1,183)] and ST-5985 [6.1% (72/1,183)], (Figure 18). Canadian isolates identified in 2013 that are highly related to ST-2400 include ST-6360 (n=12), ST-9281 (n=5) and ST-9514 (n=3) plus 14 other STs with 1 or 2 isolates in each for a total of 181 or 15.3% of isolates in the ST-2400 genogroup (STs with tbpB-563 and por alleles within 2 nucleotide base pairs of the por allele of ST-2400).

ST-2400 and ST-5985 were seen in previous years in Canada in lower numbers, however ST-9663 is a novel sequence type (Figure 19).

Figure 18. Prevalent NG-MAST Sequence Type Distribution of Neisseria gonorrhoeae Isolates Received by the NML, 2013; N=1,183Footnote a

Figure 18
   Prevalent NG-MAST Sequence Type Distribution of Neisseria gonorrhoeae Isolates Received by the NML, 2013; N=1,183 - Text Description
Figure 18. Prevalent NG-MAST Sequence Type Distribution of Neisseria gonorrhoeae Isolates Received by the NML, 2013; N=1,183Footnote a
NG-MAST No. of isolates NG-MAST No. of isolates NG-MAST No. of isolates NG-MAST No. of isolates
ST2400 143 ST2443 18 ST9171 11 ST7574 8
ST9663 87 ST8684 15 ST9363 11 ST9566 8
ST5985 72 ST432 14 ST9665 11 ST9700 8
ST1407 54 ST9523 14 ST5268 11 ST9551 7
ST3150 34 ST6734 13 ST10451 10 ST9994 7
ST3307 32 ST2212 12 ST6749 10 ST3056 6
ST4709 24 ST6360 12 ST9180 10 ST8688 6
ST3158 19 ST1696 11 ST7986 9 ST9380 6
ST8695 19 ST4995 11 ST3935 8 ST9427 6

A bar chart demonstrating the distribution of Neisseria gonorrhoeae isolates within the most prevalent sequence types (STs). Thirty-six different STs are along the horizontal axis and the vertical axis represents the number of isolates.

Figure 19. Trends of Prevalent NG-MAST Sequence Types of Neisseria gonorrhoeae Isolates Received by NML, 2010 - 2013Footnote a

Figure 19
   Trends of Prevalent NG-MAST Sequence Types of Neisseria gonorrhoeae Isolates Received by NML, 2010 - 2013 - Text Description
Figure 19. Trends of Prevalent NG-MAST Sequence Types of Neisseria gonorrhoeae Isolates Received by NML, 2010 - 2013Footnote a
NG-MAST 2010 (N=1233) 2011 (N=1158) 2012 (N=1031) 2013 (N=1183)
ST-1407 13.22% 15.11% 11.06% 4.56%
ST-3150 11.44% 1.30% 6.60% 2.87%
ST-2400 0.00% 0.43% 7.37% 12.09%
ST-3307 1.30% 9.33% 5.72% 2.70%
ST-3158 9.00% 3.80% 3.49% 1.61%
ST-3550 5.19% 5.87% 5.24% 0.34%
ST-225 5.27% 2.42% 1.75% 0.17%
ST-4266 4.06% 3.28% 0.78% 0.00%
ST-9663 0.00% 0.00% 0.00% 7.35%
ST-5985 0.08% 0.00% 0.58% 6.09%
ST-5005 3.00% 3.11% 0.10% 0.00%
ST-2992 2.43% 1.47% 2.04% 0.42%
ST-4709 0.32% 1.04% 1.94% 2.03%
ST-7986 0.00% 0.60% 4.07% 0.76%
ST-292 0.97% 1.47% 1.75% 0.42%
ST-3116 2.60% 1.30% 0.39% 0.00%
ST-3149 1.54% 1.90% 0.39% 0.34%
ST-231 2.35% 1.12% 0.00% 0.00%
ST-3935 0.24% 1.30% 1.36% 0.68%
ST-2616 0.41% 2.07% 0.78% 0.00%
ST-6749 0.00% 0.35% 2.23% 0.85%

A clustered bar chart showing the percentage of Neisseria gonorrhoeae with specific sequence types for the years specified. Each year is represented by a different colored bar. The horizontal axis represents the different STs. The vertical axis represents the percentage. The denominator for calculating the percentage is the total number of viable isolates tested by the NML for each year.

ST-1407 is an internationally identified clone that has been described as a superbug, harboring high-level resistance to cephalosporins and is threatening the last recommended first-line therapy options for gonorrhoea treatment (Allen, 2013; Unemo, 2010; Unemo, 2011; Unemo, 2012).  ST-1407 was the prevalent ST in 2010, 2011 and 2012.  In 2013, only 4.6% (54/1,183) of isolates were identified as ST-1407.  Canadian isolates identified in 2013 that are highly related to ST-1407 include ST-3158 (n=19), ST-2212 (n=12), ST-10451 (n=10), ST-9427 (n=6), plus 14 other STs with 1 to 4 isolates each.   These highly related isolates are all characterized with the tbpB-110 allele and have por alleles that differ by up to 4 nucleotide base pairs.  A total of 11.2% of isolates (132/1,183) were either ST-1407 or highly related sub-types of ST-1407.  This percentage has decreased since 2012 which had 23.6% (243/1,031) of isolates within the ST-1407 genogroup.

Distribution of STs within provinces is represented in Figures 20 and 21.  ST-2400 was identified in 6 provinces including QC [56.6% (81/143)], ON [25.9% (37/143)], BC [9.8% (14/143)], AB [6.3% (9/143)], MB [0.7% (1/143)] and NB [0.7% (1/143)].  ST-9663, the next most prevalent ST type, was identified primarily in ON [77.0% (67/87)], then QC [17.2% (15/87)], AB [3.5% (3/87)] and BC [2.3% (2/87)].  ST-5985 was identified primarily in BC [63.9% (46/72)], then AB [31.9% (23/72)], ON [2.8% (2/72)] and SK [1.4% (1/72)].

Figure 20. Provincial Distribution within Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1,183Footnote a

Figure 20

   Provincial Distribution within Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1,183 - Text Description
Figure 20. Provincial Distribution with Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1183.Footnote a
NG-MAST Alberta British Columbia Manitoba New Brunswick Nova Scotia Ontario Quebec Saskatchewan
ST-2400 9 14 1 1   37 81  
ST-9663 3 2       67 15  
ST-5985 23 46       2   1
ST-1407 1 2       21 30  
ST-3150             34  
ST-3307 1 1 1     29    
ST-4709 8 2           14
ST-3158   2       16 1  
ST-8695 4 15            
ST-2443     1     16 1  
ST-8684 1 3       11    
ST-432           13   1
ST-9523           14    
ST-6734 11 2            
ST-2212           11 1  
ST-6360           4 8  
ST-1696           2 9  
ST-4995 2 3       5 1  
ST-9171           11    
ST-9363 3 8            
ST-9665   11            
ST-5268 2 3     1 5    
ST-10451           10    
ST-6749           8 2  
ST-9180           9 1  
ST-7986           9    

A stacked bar chart demonstrating the number of Neisseria gonorrhoeae isolates from different provinces within the most prevalent sequence types. The horizontal axis is labelled with the different STs. The vertical axis represents the number of isolates. Each bar represents a different ST and is divided into different colors corresponding to different provinces.

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Figure 21. Distribution of Neisseria gonorrhoeae NG-MAST Sequence Types within Provinces, 2013; N=1,183Footnote a

Figure 21a. Distribution of NG-MAST within Alberta (N=137)

Figure 21
   Distribution of NG-MAST within Alberta (N=137) - Text Description
Figure 21a. Distribution of NG-MAST within Alberta (N=137)
NG-MAST Number
ST-5985 23
ST-6734 11
ST-2400 9
ST-4709 8
ST-9766 5
ST-8695 4
ST-9551 4
ST-8688 4
ST-6154 4
ST-9663 3
ST-9363 3
ST-9797 3
Other 56

Figure 21b.  Distribution of NG-MAST within British Columbia (N=170)

Figure 21
   Distribution of NG-MAST within British Columbia (N=170) - Text Description
Figure 21b. Distribution of NG-MAST within British Columbia (N=170)
NG-MAST Number
ST-5985 46
ST-8695 15
ST-2400 14
ST-9665 11
ST-9363 8
ST-8684 3
ST-4995 3
ST-5268 3
ST-7574 3
ST-9663 2
ST-1407 2
Other 60

Figure 21c. Distribution of NG-MAST within Saskatchewan (N=67)

Figure 21c
   Distribution of NG-MAST within Saskatchewan (N=67) - Text Description
Figure 21c. Distribution of NG-MAST within Saskatchewan (N=67)
NG-MAST Number
ST-4709 14
ST-9427 6
ST-3935 5
ST-292 5
ST-3657 4
ST-4637 4
ST-3654 3
ST-8688 2
ST-210 2
ST-3656 2
ST-8853 2
ST-9649 2
ST-5985 1
Other 15

Figure 21d. Distribution of NG-MAST within Ontario (N=498)

Figure 21d
   Distribution of NG-MAST within Ontario (N=498) - Text Description
Figure 21d. Distribution of NG-MAST within Ontario (N=498)
NG-MAST Number
ST-9663 67
ST-2400 37
ST-3307 29
ST-1407 21
ST-3158 16
ST-2443 16
ST-9523 14
ST-432 13
ST-8684 11
ST-2212 11
ST-9171 11
Other 252

Figure 21e. Distribution of NG-MAST within Quebec (N=302)

Figure 21e
   Distribution of NG-MAST within Quebec (N=302) - Text Description
Figure 21e. Distribution of NG-MAST within Quebec (N=302)
NG-MAST Number
ST-2400 81
ST-3150 34
ST-1407 30
ST-9663 15
ST-1696 9
ST-6360 8
ST-9994 7
ST-3056 6
ST-9380 6
ST-9566 5
ST-4473 5
Other 96

Five pie charts, one for each of the following above provinces. Each pie chart is divided into 12 to 14 segments representing the proportion of specific NG-MAST sequence types found in that province. Provinces with fewer Neisseria gonorrhoeae isolates did not have pie charts but are mentioned in a note.

Figure 22 provides a distribution of resistance characterizations among specific ST types.  ST-2400 and ST-9663 are predominantly comprised of multi-drug resistant profiles including CMRNG/Probable CMRNG along with CipR and/or CeDS and/or CxDS.

Figure 22. Distribution of Resistance Characterizations within Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1,183Footnote a

Figure 22
   Distribution of Resistance Characterizations within Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1,183 - Text Description
Figure 22. Distribution of Resistance Characterizations within Neisseria gonorrhoeae NG-MAST Sequence Types, 2013; N=1,183Footnote a
NG-MAST CxDS/CipR and CxDS/CipR/TetR and CeDS/CxDS/CipR/TetR CipR and CipR/EryR/TetR and CipR/EryR and CipR/TetR and CipR/PenR and CipR/PenR/TetR and EryR/TetR PPNGs &/or TRNGs with other antibiotic resistances including CMRNG TRNG/CipR/EryR/CxDS and TRNG/CipR/CxDS Probable CMRNG/CipR and Probable CMRNG/AziR Probable CMRNG/CxDS/CipR CMRNG/AziR/CipR and CMRNG/CipR CMRNG/CipR with or without AziR but with CeDS and/or CxDS Total
ST-2400 1 13 1   65 1 57 5 143
ST-9663   19     21   46 1 87
ST-5985   1 69       1   71
ST-1407   4     4   28 18 54
ST-3150   23     3   8   34
ST-3307   1 29 1       1 32
ST-4709   1     6   17   24
ST-3158   2       1 8 8 19
ST-8695             15 4 19
ST-2443         1 8   9 18
ST-8684     15           15
ST-432   1     5   7 1 14
ST-9523   14             14
ST-6734   10     1   2   13
ST-2212 1       1   3 7 12
ST-6360   6     4   2   12
ST-1696   10     1       11
ST-4995     10   1       11
ST-9171     10 1         11
ST-9363         6   5   11
ST-9665     11           11
ST-10451             8 2 10
ST-6749     10           10
ST-9180   4     3 1 2   10
ST-5268     9           9
ST-7986 1 6         2   9
ST-3935   7     1       8

A stacked bar chart demonstrating the antimicrobial characterization of Neisseria gonorrhoeae isolates within the most prevalent sequence types. The horizontal axis is labelled with the different STs. The vertical axis represents the number of isolates. Each bar represents a different ST and is divided into different colors corresponding to different antimicrobial characterizations.

Figure 23 outlines the NG-MAST sequence types of isolates with decreased susceptibility to cefixime (Figure 23a), decreased susceptibility to ceftriaxone (Figure 23b), azithromycin resistant isolates (Figure 23c) and susceptible isolates (Figure 23d).

The most prevalent ST of isolates with decreased susceptibility to cefixime was ST-1407 [23.21% (13/56)] followed by ST-9551 [12.5% (7/56)] and ST-3158 [10.7% (6/56)] (Figure 23a). 

Isolates with decreased susceptibility to ceftriaxone were primarily ST-2443 [15.2% (17/112)] and ST-1407 [14.3% (16/112)] with ST-2212 and ST-3158 [7.1% (8/112)] following (Figure 23b).

The ST types identified among the AziR isolates are displayed in Figure 23c.  ST-3158 [27.0% (10/37)] and ST-9427 [16.2% (6/37)] are the most prevalent.  The STs of the susceptible isolates available for testing were distributed somewhat uniformly with ST-292 and ST-3657 each with 13.3% (4/30), (Figure 23d). 

Figure 23. NG-MAST Sequence Types of 2013  Neisseria gonorrhoeae IsolatesFootnote a

Figure 23a. Decreased Susceptibility to Cefixime (MIC ≥ 0.25 mg/L), N=56

Figure 23a
   Decreased Susceptibility to Cefixime (MIC ≥ 0.25 mg/L), n=56 - Text Description
Figure 23a. Decreased Susceptibility to Cefixime (≥0.25 mg/L), N=56
NG-MAST Percentage
*Other sequence types contain 1 or 2 isolates each
ST-1407 (n=13) 23.2%
ST-9551 (n=7) 12.5%
ST-3158 (n=6) 10.7%
ST-2212 (n=5) 8.9%
ST-4275 (n=4) 7.1%
ST-10451 (n=2) 3.6%
ST-3149 (n=2) 3.6%
ST-4269 (n=2) 3.6%
*Other (n=15) 26.8%
Total (n=56) 100.0%

Figure 23b. Decreased Susceptibility to Ceftriaxone (MIC ≥ 0.125 mg/L), N=112

Figure 23b
   Decreased Susceptibility to Ceftriaxone (MIC ≥ 0.125 mg/L), N=112 - Text Description
Figure 23b. Decreased Susceptibility to Ceftriaxone (MIC ≥ 0.125 mg/L), N=112
NG-MAST Percentage
*Other sequence types contain 1 or 2 isolates each
ST-2443 (n=17) 15.2%
ST-1407 (n=16) 14.3%
ST-2212 (n=8) 7.1%
ST-3158 (n=8) 7.1%
ST-2400 (n=7) 6.3%
ST-9551 (n=7) 6.3%
ST-4269 (n=4) 3.6%
ST-8695 (n=4) 3.6%
ST-2345 (n=3) 2.7%
ST-3149 (n=3) 2.7%
ST-4275 (n=3) 2.7%
*Other (n=32) 28.6%
Total (n=112) 100.0%

Figure 23c. Azithromycin Resistant (MIC ≥ 2 mg/L), N=37

Figure 23c
   Azithromycin Resistant (MIC ≥ 2 mg/L), N=37 - Text Description
Figure 23c. Azithromycin Resistant (MIC ≥ 2 mg/L), N=37
NG-MAST Percentage
*Other sequence types contain 1 or 2 isolates each
ST-3158 (n=10) 27.0%
ST-9427 (n=6) 16.2%
ST-9368 (n=3) 8.1%
ST-2992 (n=2) 5.4%
ST-6765 (n=2) 5.4%
ST-8915 (n=2) 5.4%
*Other (n=12) 32.4%
Total (n=37) 100.0%

Figure 23d. Susceptible Isolates, N=30

Figure 23d
   Susceptible Isolates, N=30 - Text Description
Figure 23d. Susceptible Isolates, N=30
NG-MAST Percentage
*Other sequence types contain 1 or 2 isolates each
ST-292 (n=4) 13.3%
ST-3657 (n=4) 13.3%
ST-4637 (n=3) 10.0%
ST-2 (n=2) 6.7%
ST-210 (n=2) 6.7%
ST-3656 (n=2) 6.7%
ST-8853 (n=2) 6.7%
ST-9649 (n=2) 6.7%
*Other (n=9) 30.0%
Total (n=30) 100.0%

Four bar charts, one for each of the following types of Neisseria gonorrhoeae isolates: decreased susceptibility to cefixime, decreased susceptibility to ceftriaxone, resistant to azithromycin and susceptible to all antibiotics tested. The horizontal axis of each chart is labelled with the STs and the bars represent the percentage of the STs within the phenotype of that chart.

Plasmids

Plasmid profiles for PPNG, TRNG and PPNG/TRNG isolates are shown in Figure 24.  The beta-lactamase gene was encoded in three different types of plasmids of sizes 3.05 megadaltons (Mda), 3.2 Mda and 4.5 Mda. In 2013, the 3.2 Mda plasmid was the most common type amongst the 36 PPNG strains isolated at 69.4% (25/36), followed by the 3.05 Mda plasmid at 27.8% (10/36) and then the 4.5 Mda plasmid at 2.8% (1/36). These plasmids co-existed with the 2.6 Mda cryptic plasmid and sometimes with the 24.5 Mda conjugal plasmid. The 3.2 Mda plasmid is also the most common β-lactamase encoding plasmid in PPNG/TRNG strains at 74.0% (74/100). The 25.2 Mda plasmid that encodes tetracycline resistance (TetM) co-existed with the cryptic plasmids in most TRNG and PPNG/TRNG strains. Among the TRNG isolates tested in 2013, 61.9% (112/181) had the 2.6 and 25.2 Mda plasmids. TRNG isolates accounted for 88.6% of all the plasmid mediated resistance in N. gonorrhoeae in 2013 (281/317 PPNG, PPNG/TRNG and TRNG strains).

Figure 24. Plasmid Distribution within Antimicrobial Classifications of Neisseria gonorrhoeae Isolates Received by the NML, 2013

Figure 24a. PPNG (N=36)

Figure 24a
   Figure 24a. PPNG (N=36) - Text Description
Figure 24a. PPNG (N=36)
Plasmid Profile Percentage
2.6 - 3.05 - 24.5 (n=10) 27.8%
2.6 - 3.2 - 24.5 (n=14) 38.9%
2.6 - 3.2 (n=11) 30.6%
2.6 - 4.5 (n=1) 2.8%

Figure 24b. PPNG/TRNG (N=100)

Figure 24b
   Figure 24b. PPNG/TRNG (N=100) - Text Description
Figure 24b. PPNG/TRNG (N=100)
Plasmid Profile Percentage
2.6 - 3.2 - 25.2 (n=73) 73.0%
2.6 - 4.5 - 25.2 (n=17) 17.0%
2.6 - 3.05 - 25.2 (n=9) 9.0%
3.2 - 25.2 (n=1) 1.0%

Figure 24c. TRNG (N=181)

Figure 24c
   Figure 24c. TRNG (N=181) - Text Description
Figure 24c. TRNG (N=181)
Plasmid Profile Percentage
2.6 - 25.2 (n=111) 61.3%
25.2 (n=69) 38.1%
2.6 - 3.05 - 25.2 (n=1) 0.6%

Three pie charts, one for each of the following antimicrobial classifications of Neisseria gonorrhoeae isolates: PPNG, PPNG/TRNG and TRNG. Each pie is divided into segments representing the proportion of plasmid combinations found within that classification.

Conclusion

The evolution of antimicrobial resistance in gonorrhoea is complex and the emergence and spread of resistant isolates is a recognized global public health threat. It is imperative that surveillance and monitoring of the antimicrobial susceptibilities and sequence types of N. gonorrhoeae continue to inform and subsequently mitigate the impact of antimicrobial resistance in gonorrhoea. It is important to monitor changes in the characteristics and prevalence of the resistant isolate populations and their spread across the country in order to guide therapeutic recommendations.  Reports of cefixime treatment failures and the observed MIC creep between 2001 and 2010 for both cefixime (from 0.016 mg/L to 0.125 mg/L) and ceftriaxone (from 0.016 mg/L to 0.063 mg/L) led to gonorrhoea treatment changes.  In 2011, The Canadian STI Guidelines issued updated recommendations for the use of combination gonorrhoea therapy with 250 mg ceftriaxone intramuscularly and azithromycin 1 g orally as the first-line regimen in men-who-have-sex-with men (MSM) and in pharyngeal infections (Public Health Agency of Canada, 2011).  The United States (CDC, 2012) and Europe (Bignell, 2013) also updated treatment recommendations to combination therapy with intramuscular ceftriaxone and oral azithromycin.  Since the 2011 changes to gonorrhoea treatment recommendations in Canada there has been a decrease in the proportion of isolates with elevated MICs to the cephalosporins.  In 2011, 7.6% of isolates exhibited decreased susceptibility to ceftriaxone and/or cefixime according to the WHO definition (decreased susceptibility MICs ≥0. 25 mg/L for cefixime and ≥0.125 mg/L for ceftriaxone).  This decreased to 5.9% in 2012 and further declined to 3.9% of isolates tested in 2013. Similarly, the US reported declines to decreased cefixime susceptibility from 3.9% in 2010 to 2.9% in the first half of 2012 (Kirkcaldy, 2013). The UK reported the prevalence of isolates with decreased cefixime susceptibilitydropped from 17.1% in 2010 to 10.8% in 2011 (Ison, 2013).

Enhancing surveillance to include linked epidemiological and laboratory data will assist with the limitations in the current passive surveillance system regarding data representativeness and interpretation.  These improvements to the gonococcal surveillance program are expected with the ESAG (Enhanced Surveillance of Antimicrobial Resistant Gonorrhoea) program beginning in 2014.

These gonococcal surveillance data will be utilized in the future iterations of the Canadian STI guidelines to provide information on the most effective treatment of N. gonorrhoeae and to reduce the prevalence and spread of drug resistant gonorrhoea. This surveillance is particularly important as molecular testing, which provides no susceptibility data becomes the most commonly used method for the diagnosis of N. gonorrhoeae in Canada.

Appendix

Appendix A

Neisseria gonorrhoeae culture isolates in Canada, 2009 – 2013Footnote a
Province 2009 GC Cultures 2010 GC Cultures 2011 GC Cultures 2012 GC Cultures 2013 GC Cultures
Tested in each province Received at NML % Sent to NML for Testing Tested in each province Received at NML % Sent to NML for Testing Tested in each province Received at NML % Sent to NML for Testing Tested in each province Received at NML % Sent to NML for Testing Tested in each province Received at NML % Sent to NML for Testing
British Columbia 296 183 61.8% 342 256 74.9% 490 176 35.9% 372 92 24.7% 454 170 37.4%
Alberta 383 91 23.5% 283 164 58.0% 457 156 34.1% 497 94 18.9% 514 134 26.1%
Saskatchewan 36 30 83.3% 35 11 31.4% 35 35 100% 57 57 100% 69 67 97.1%
Manitoba 34 3 8.8% 24 11 45.8% 31 12 38.7% 49 8 16.3% 29 7 24.1%
Ontario 1,383 383 27.7% 1,101 383 34.8% 1,212 428 35.3% 1,218 403 33.1% 1404 498 35.5%
Québec 959 216 22.5% 1,100 335 30.5% 1,045 282 27.0% 838 390 46.5% 716 298 41.6%
New Brunswick 11 4 36.4% 9 9 100% 12 6 50.0% 3 3 100% 5 5 100%
Nova Scotia 103 2 1.9% 69 69 100% 77 77 100% 0 0 n/a 1 1 100%
Newfoundland 2 2 100% 7 7 100% 1 0 0% 1 0 0% 1 1 100%
Prince Edward Island 0 0 n/a 0 0 n/a 0 0 n/a 1 1 100% 2 2 100%
Totals 3,207 914 28.5% 2,970 1,245 41.9% 3,360 1,172 34.9% 3,036 1,048 34.5% 3,195 1,183 37.0%

Appendix B

Characterization of all Neisseria gonorrhoeae Isolates Submitted to the NML, 2009 - 2013
Characterization 2009 2010 2011 2012 2013 Totals
Plasmid Mediated Resistances PPNG 8 7 2 3 3 23
PPNG/CipR 11 10 9 6 10 46
PPNG/EryR 2 1 6 1 11 21
PPNG/EryR/CipR 0 1 0 2 0 3
PPNG/TetR 3 1 0 2 0 6
PPNG/TetR/CipR 2 1 1 4 4 12
PPNG/CMRNG 0 0 2 2 4 8
PPNG/CMRNG/CipR 3 3 6 10 4 26
PPNG/CMRNG/CxDS/CipR 0 0 1 0 0 1
PPNG/TRNG 11 0 2 11 18 42
PPNG/TRNG/CeDS/CipR 0 0 2 0 0 2
PPNG/TRNG/CeDS/CipR/EryR 0 0 6 0 0 6
PPNG/TRNG/CeDS/CxDS/CipR/EryR 0 0 3 0 0 3
PPNG/TRNG/CipR 33 32 43 49 43 200
PPNG/TRNG/EryR 1 0 0 0 3 4
PPNG/TRNG/CipR/EryR 4 7 34 22 34 101
PPNG/TRNG/CxDS/CipR/EryR 0 2 14 0 0 16
PPNG/TRNG/AziR/CipR/EryR 1 0 0 0 1 2
PPNG/TRNG/AziR/CipR/CxDS/EryR 1 1 0 0 0 2
TRNG 28 12 21 36 86 183
TRNG/CipR 12 22 15 16 29 94
TRNG/CipR/CxDS 0 0 0 0 1 1
TRNG/CipR/EryR 4 11 36 47 42 140
TRNG/CipR/EryR/CeDS 0 0 1 0 0 1
TRNG/CipR/EryR/CeDS/CxDS 0 0 1 0 0 1
TRNG/CipR/EryR/CxDS 0 0 8 0 1 9
TRNG/CxDS 0 0 0 1 0 1
TRNG/EryR 5 6 1 1 13 26
TRNG/CipR/PenR 0 0 1 0 2 3
TRNG/CxDS/CipR 0 0 1 1 1 3
TRNG/CMRNG 0 0 0 1 2 3
TRNG/CMRNG/CipR 2 1 2 2 4 11
TRNG/CMRNG/CxDS/CipR 0 1 2 3 0 6
TRNG/PenR 0 0 1 1 1 3
Total 131 119 221 221 317 1,009
Chromosomal Mediated Resistances AziR/EryR 0 21 5 0 3 29
AziR/EryR/TetR 1 2 2 14 8 27
AziR/CipR/EryR 0 0 0 0 1 1
AziR/EryR/PenR 0 0 1 0 0 1
AziR/CipR/EryR/TetR 0 0 0 0 2 2
AziR/CeDS/CipR/EryR/TetR 0 0 0 0 1 1
CeDS/CipR/EryR 0 1 0 0 0 1
CeDS/CipR/TetR 0 0 0 1 0 1
CeDS/CxDS/CipR 0 0 0 0 1 1
CeDS/CxDS/CipR/PenR 0 0 0 0 2 2
CeDS/CxDS/CipR/TetR 0 0 0 0 3 3
CeDS/CxDS/CipR/PenR/TetR 0 0 0 0 1 1
CeDS/CipR/PenR/TetR 0 0 1 0 0 1
CxDS/CipR/EryR/TetR 0 0 1 1 0 2
CipR 40 54 34 44 51 223
CipR/CeDS 0 0 0 0 1 1
CipR/CxDS 0 1 0 0 2 3
CipR/EryR 37 10 16 3 2 68
CipR/EryR/TetR 8 15 9 4 34 70
CipR/PenR 0 0 0 0 2 2
CipR/PenR/TetR 0 0 0 2 2 4
CipR/TetR 26 26 23 56 70 201
CipR/TetR/CxDS 0 1 0 3 2 6
EryR 1 0 9 3 3 16
EryR/TetR 0 3 16 10 13 42
PenR 1 0 0 0 1 2
PenR/TetR 0 0 0 0 2 2
TetR 9 9 17 21 8 64
CMRNG 3 3 2 4 26 38
CMRNG/AziR/CipR 8 8 5 5 7 33
CMRNG/AziR/CeDS/CxDS/CipR 0 0 0 1 4 5
CMRNG/AziR/CipR/CxDS 0 2 0 6 2 10
CMRNG/AziR/CeDS/CipR 0 0 0 0 1 1
CMRNG/CipR 367 443 387 294 295 1,786
CMRNG/AziR 0 1 0 0 4 5
CMRNG/CeDS/CipR 3 8 32 7 6 56
CMRNG/CeDS/CxDS/CipR 32 79 88 55 30 284
CMRNG/CxDS/CipR 60 104 80 92 43 379
Probable CMRNG 6 4 3 9 6 28
Probable CMRNG/AziR 0 0 0 0 1 1
Probable CMRNG/AziR/CipR 0 2 0 0 2 4
Probable CMRNG/CeDS 0 0 0 1 0 1
Probable CMRNG/CipR 137 194 110 123 174 738
Probable CMRNG/CeDS/CipR 0 0 5 2 1 8
Probable CMRNG/CeDS/CxDS/CipR 0 10 1 1 5 17
Probable CMRNG/CxDS/CipR 3 17 7 4 14 45
Susceptible Strain 40 96 83 44 30 293
Total 782 1,114 937 810 866 4,509
Total 913 1,233 1,158 1,031 1,183 5,518

References

  • Allen VG, Mitterni L, Seah C, Rebbapragada A, Martin IE, Lee C, Siebert H, Towns L, Melano RG, Lowe DE. 2013. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA 2013;309:163-170.
  • Barry, PM and Klausner, JD. The use of cephalosporins for gonorrhoea: The impending problem of resistance. Expert Opin Pharmacother 2009;10:555–577.
  • Bignell C, Unemo M; European STI Guidelines Editorial Board.  2012 European guideline on the diagnosis and treatment of gonorrhoea in adults.  Int J STD AIDS 2013;24:85-92.
  • Centers for Disease Control and Prevention.  Sexually Transmitted Disease Surveillance 2007 Supplement, gonococcal Isolate Surveillance Project (GISP) Annual report 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, March 2009. Available: http//www.cdc.gov/sth/GISP2007/.
  • Centers for Disease Control and Prevention.  Antibiotic Resistance Threats in the United States, 2013.  Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.  Available: www.cdc.gov/drugresistance/threat-report-2013/.
  • Chisholm SA, Neal TJ, Alawattegama AB, Birley HDL, Howe RA, Ison CA. Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales. J Antimicrob Chemother 2009;64:353-358.
  • Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Third Informational Supplement M100-S24 vol. 34.  Clinical and Laboratory Standards Institute. Wayne, PA, 2014.
  • Ehret JM, Nims LJ, Judson FN.  A clinical isolate of Neisseria gonorrhoeae with in vitro resistance to erythromycin and decreased susceptibility to azithromycin. Sex Transm Dis 1996;23:270-272.
  • Golparian D, Hellmark B, Fredlund H, Unemo M. Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden. Sex Transm Infect 2010;86:454-460.
  • Ison CA, Hussey J, Sankar KN, Evans J, Alexander S. Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill 2011; 16(14):pii=19833.
  • Ison CA, Town K, Obi C, Chisholm S, Hughes G, Livermore DM, Lowndes CM; GRASP collaborative group.  Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis 2013;13:762-8.
  • Kirkcaldy RD, Kidd S, Weinstock HS, Papp JR, Bolan GA.  Trends in antimicrobial resistance in Neisseria gonorrhoeae in the USA: the Gonococcal Isolate Surveillance Project (GISP), January 2006-June 2012.  Sex Transm Infect  2013 Dec;89 Suppl 4:iv5-10.
  • Martin IMC, Ison CA, Aanensen DM, Fenton KA, Spratt BG. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis 2004;189:1497-1505.
  • Pandori M, Barry PM, Wu A, Ren A,, Whittington WLH, Liska S, Klausner JD. Mosaic penicillin-binding protein 2 in Neisseria gonorrhoeae isolates collected in 2008 in San Francisco, California. Antimicrob Agents Chemother 2009;53:4032-4034.
  • Public Health Agency of Canada, 2011. Important Notice – Public Health Information Update on the Treatment of Gonococcal Infection.  Available at:  http://www.phac-aspc.gc.ca/std-mts/sti-its/alert/2011/alert-gono-eng.php.
  • Public Health Agency of Canada.2014. Notifiable Diseases On-Line. http://dsol-smed.phac-aspc.gc.ca/dsol-smed/ndis/charts.php?c=pl Accessed: 04 Sept 2014.
  • Tapsall J.  Antibiotic resistance in Neisseria gonorrhoeae is diminishing available treatment options for gonorrhoea: some possible remedies. Expert Rev Anti Infect Ther 2006;4:619-628.
  • Tapsall JW, Ray S, Limnios A. Characteristics and population dynamics of mosaic penA allele-containing Neisseria gonorrhoeae isolates collected in Sydney, Australia, in 2007-2008. Antimicrob Agents Chemother 2010;54:554-556.
  • Unemo M, Golparian D, Syversen G, Vestrheim DF, Moi H. Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment, Norway, 2010. Euro Surveill 2010;15(47): pii=19721.
  • Unemo M, Golparian D, Hestner A. Ceftriaxone treatment failure of pharyngeal gonorrhoeae verified by international recommendations.  Sweden, July 2013.  Euro Surveill 2011:16:pii=19792. 
  • Unemo M, Golparian D, Potočnik M, Jeverica S. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill 2012;17(25):pii=20200.
  • World Health Organization (WHO).  Emergence of multi-drug resistant Neisseria gonorrhoeae – Threat of global rise in untreatable sexually transmitted infections.  2011.  Available from:  http://whqlibdoc.who.int/hq/2011/WHO_RHR_11.14_eng.pdf.  Accessed 6 May 2011.
  • World Health Organization (WHO).  Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae . 2012.  Available from:  http://www.who.int/reproductivehealth/publications/rtis/9789241503501/en/.  Accessed 22 May 2012.
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