National Surveillance of Antimicrobial Susceptibilities of Neisseria gonorrhoeae - Annual Summary 2014

Download the alternative format
(PDF format, 1.57 MB, 45 pages)

Organization: Public Health Agency of Canada

Type: Annual Summary

Date published: 2016-03-10

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, Dr. Aboubakar Mounchili, Stephanie Totten, Lily Fang
  • Professional Guidelines and Public Health Practice Division
    Centre for Communicable Diseases and Infection Control
    Public Health Agency of Canada
    • 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. Mel Krajden, Dr. Linda Hoang, Ana Paccagnella
    • Provincial Laboratory of Public Health Alberta, Edmonton, Alberta:
      • Dr. Graham Tipples, Dr. Greg Tyrrell, Dr. Prenilla Naidu, Dr. Steven Drews, Donna Burton, LeeAnn Turnbull, Dawn Coppock
    • 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, Deirdre Soares, Susan Bending, Ann Maki, Dayle Noda, Hema Champaneria
    • Laboratoire de santé publique du Québec, Ste-Anne-de-Bellevue, Québec:
      • Dr. Jean Longtin, Dr. Brigitte Lefebvre, Nadia Zaid
    • 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 2010 - 2014.
  • The Canadian reported rate of gonorrhea is on the rise and has more than doubled from 15.0 per 100,000 in 1997 to 39.3 per 100,000 in 2013.  Gonorrhoea is the second most commonly reported bacterial sexually transmitted infection in Canada with 13,786 cases reported in 2013.
  • 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 2014, a total of 3,809 N. gonorrhoeae isolates were cultured in public health laboratories across Canada; 2,101 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.
  • 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 3.1% (119/3,809) in 2014.  This number represents a decrease from 3.9% (123/3,195) in 2013, 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 1.1% (42/3,809) in 2014.
  • Isolates with decreased susceptibility to ceftriaxone have declined from a high of 7.3% (218/2,970) in 2010 to 2.7% (101/3,809) in 2014.
  • 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.  Between 2013 and 2014, azithromycin resistant isolates increased to 3.3% (127/3,809), including 38 isolates from an outbreak (ST-10567). The proportion of azithromycin resistant isolates excluding the outbreak isolates is 2.3% (89/3,809).
  • 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 decreasing to 34.0% (1,296/3,809) in 2014.
  • In 2014, 32.0% (1,219/3,809) of the isolates were resistant to erythromycin; 18.2% (693/3,809) were resistant to penicillin; 47.3% (1,809/3,809) were resistant to tetracycline.
  • 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 2014, 380 different sequence types (STs) were identified among the 2,101 isolates tested and the most common sequence types wereST-2400,ST-5985 andST-10451 at 14.1%, 14.0% and 9.8%, respectively.

Introduction

Neisseria gonorrhoeae is the causative agent of gonorrhoea and is the second most commonly reported bacterial sexually transmitted infection in Canada, with 13,786 cases reported in 2013 (Public Health Agency of Canada, 2015). Rates of reported cases of gonorrhea have more than doubled from 15.0 cases per 100,000 population in 1997 to 39.3 cases per 100,000 population in 2013  (Public Health Agency of Canada, 2015). Globally, gonorrhea 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 gonorrhea 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 gonorrhea 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 gonorrhea 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 gonorrhea (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 Gonorrhea (ESAG) pilot was initiated in 2014.  This sentinel public health practice and surveillance study for N. gonorrhoeae collects 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 treatment failure. Both antimicrobial susceptible and resistant strains of gonorrhea 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 2014, provincial public health laboratories submitted a total of 2,101 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.

N. gonorrhoeae isolates are submitted to the NML primarily 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 that will inhibit the growth of the organism) was determined using agar dilution, and interpretations were based on the criteria outlined in Table 2.   Resistance characterization definitions are provided in Table 3.

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 & 5).

Isolates were 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 to determine the sequence types (ST).

Table 1.  A Summary of the Neisseria gonorrhoeae culture isolates received by the NML, 2010-2014Table 1 note aTable 1 note bTable 1 note c
ProvinceTable 1 note a 2010 2011 2012 2013 2014 Total
British Columbia 256 176 92 170 375 1,069
Alberta 164 156 94 136 382 932
Saskatchewan 11 35 57 67 93 263
Manitoba 11 12 8 7 46 84
Ontario 383 428 403 498 893 2,605
Québec 335 282 390 301 432 1,740
New Brunswick 9 6 3 5 3 26
Nova Scotia 69 77 0 1 15 162
Newfoundland 7 0 0 1 9 17
Prince Edward Island 0 0 1 2 0 3
Total isolates received at NML 1,245 1,172 1,048 1,188 2,248 6,901
Total viable isolates available for testing 1,233 1,158 1,031 1,183 2,101 6,706
Total isolates resistant to at least one antibiotic 1,137 1,075 987 1,153 1,955 6,347
Total number of isolates tested in each provinceTable 1 note b 2,970 3,360 3,036 3,195 3,809 16,370
Percentage of isolates resistant to at least one antibiotic 38.3% 32.0% 32.5% 36.1% 51.3% 38.8%
Percentage of total cases tested 26.1% 29.5% 24.2% 23.2% 27.6%Table 1 note c 27.2%
Total cases reported in Canada 11,397 11,394 12,561 13,786 13,786Table 1 note c 60,138
Table 2. Neisseria gonorrhoeae Antimicrobial Resistance CriteriaTable 2 note aTable 2 note b
Antibiotic Recommended Testing Concentration Ranges (mg/L) MIC Interpretive Standard (mg/L)Table 2 note a Source of Antibiotics
S DS I R
Penicillin 0.032 - 128.0 ≤ 0.06   0.12- 1.0 ≥ 2.0 Sigma
Tetracycline 0.064 - 64.0 ≤ 0.25   0.5 - 1.0 ≥ 2.0 Sigma
Erythromycin 0.032 - 32.0 ≤ 1.0     ≥ 2.0 Sigma
Spectinomycin 4.0 - 256.0 ≤ 32.0   64 ≥ 128.0 Sigma
Ciprofloxacin 0.001 - 64.0 ≤ 0.06   0.12 - 0.5 ≥ 1.0 Bayer Health Care
Ceftriaxone 0.001 - 2.0   ≥ 0.125     Sigma
Cefixime 0.002 - 2.0   ≥ 0.25     Sigma
Azithromycin 0.016 - 32.0 ≤ 1.0     ≥ 2.0 Pfizer
Ertapenem 0.002 - 2.0 Interpretive Standards Not Available Sequoia
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 Susceptibility  to Ceftriaxone Cx MIC ≥ 0.125 mg/L
CeDS Neisseria gonorrhoeae with Decreased Susceptibility  to Cefixime Ce MIC ≥ 0.25 mg/L

Results and Discussion

In 2014, a total of 3,809 N. gonorrhoeae isolates were cultured in public health laboratories across Canada; 2,101 of these were submitted to the NML and found viable for antimicrobial susceptibility testing.  A total of 1,955 of submitted isolates were found to be resistant to at least one antibiotic tested representing an increase from 36.1% (1,153/3,195) in 2013 to 51.3% (1,995/3,809) in 2014  (Figure 1). The characterization of each resistant N. gonorrhoeae isolate is provided in Appendix B. Of all the gonorrhea cases reported in 2014 (approximated at over 13,000 cases), approximately 70% were diagnosed by NAAT for which there is no antimicrobial susceptibility data.

Gender and age data were available for 99.8% (2,098/2,101) of isolates tested at the NML (Table 4).  Of these, 87.4% (1,833/2,098) were males ranging from infant to 83 years of age.  A total of 12.6% (265/2,098) of isolates were from females ranging from infancy to 71 years.

Anatomic source data was available for 99.8% (2,098/2,101) of the isolates sent to the NML (Table 5). Of these, 50.2% (1,053/2,098) were urethral, 23.4% (490/2,098) were rectal, 14.8% (311/2,098) were from the throat, 6.3% (133/2,098) were cervical, 3.0% (62/2,098) were vaginal and 2.1% (44/2,098) were from other sources.  Three infants and 1 child were diagnosed with gonorrhea of the eye.

Table 4. Demographic Data for the Neisseria gonorrhoeae isolates tested at the NML, 2014 (N=2,101)
Age Male Female Not Specified Totals
Under 15 2 13 0 15
15 - 20 148 53 0 201
21 - 25 451 70 3 524
26 - 35 681 74 0 755
36 - 45 282 31 0 313
46 - 55 189 14 0 203
56 - 65 64 8 0 72
66 + 16 2 0 18
Not Specified 0 0 0 0
Total 1,833 265 3 2,101
Table 5. Anatomic Isolation Sites for the Neisseria gonorrhoeae isolates tested at the NML, 2014 (N=2,101)
Isolation Site Male Female Not Specified Totals
Penis/ Urethra 1,053 N/A 0 1,053
Rectum 473 14 3 490
Throat 268 43 0 311
Cervix N/A 133 0 133
Vagina N/A 62 0 62
Eye 1 3 0 4
Other 35 9 0 44
Not Specified 3 1 0 4
Total 1,833 265 3 2,101

Figure 1. Neisseria gonorrhoeae Isolates in Canada, 2010 to 2014Figure 1 note a

Text description follows.
Description - Figure 1

Stacked column graph showing the number of Neisseria gonorrhoeae isolates in Canada from 2000 to 2014.  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.

Gonorrhea cases Year
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Number of gonorrhea cases diagnosed by nucleic acid amplification testing (NAAT) 1,731 2,165 2,900 4,006 5,299 5,580 7,133 7,598 8,816 8,072 8,427 8,034 9,525 8,805 9,977
Number of gonorrhea cases diagnosed by culture and found susceptible by provincial labaoratories 3,366 3,491 3,539 3,532 3,216 2,714 2,729 2,880 2,978 2,233 1,832 2,284 2,049 2,042 1,814
Number of gonorrhea cases diagnosed by culture and found resistant by provincial laboratories and confirmed by NML 1,092 1,100 926 703 802 905 1,472 1,395 929 873 1,138 1,076 987 1,153 1,995
Total 6,189 6,756 7,365 8,241 9,317 9,199 11,334 11,873 12,723 11,178 11,397 11,394 12,561 13,786 13,786

Trends in Antimicrobial Sensitivies

In 2014, 12.6% (480/3,809) 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 1.4% (52/3,809) and Tetracycline Resistant Neisseria gonorrhoeae (TRNG) for 10.7% (406/3,809) of isolates (Figure 2).

Figure 2. Trends of PPNG, TRNG, CMRNG, Probable CMRNG Neisseria gonorrhoeae in Canada from 2010 to 2014Figure 2 note a

Text description follows.
Description - Figure 2

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.

Characterization Year
2010 2011 2012 2013 2014
PPNG 0.71% 0.54% 0.59% 0.88% 1.37%
TRNG 1.72% 2.56% 3.39% 5.48% 10.68%
PPNG/TRNG 1.41% 3.1% 2.70% 3.13% 2.86%
PPNG/CMRNG 0.1% 0.27% 0.40% 0.25% 0.32%
TRNG/CMRNG 0.07% 0.12% 0.20% 0.19% 0.26%
CMRNG 21.82% 17.68% 15.28% 13.08% 12.60%
Probable CMRNG 7.64% 3.75% 4.61% 6.35% 9.71%

Figure 3 shows the trends of antimicrobial susceptibilities of N. gonorrhoeae tested in Canada from 2004 to 2014.

Penicillin resistance increased from 6.0% (242/4,018) in 2004, to 25.1% (744/2,970) in 2010 and then decreased to 18.2% (693/3,809) in 2014. Tetracycline resistance increased from 17.8% (715/4,018) in 2004 to 34.6% (1,028/2,970) in 2010.  Between 2013 and 2014, tetracycline resistance increased from 33.0% (1054/3,195) to 47.3% (1,803/3,809). In 2004, only 9.3% (373/4,018) of Canadian isolates were found to be erythromycin resistant.  This percentage increased to 32.0% (1,219/3,809) in 2014. The percentage of ciprofloxacin resistant isolates increased from 6.3% (251/4,018) in 2004 to 34.0% (1,296/3,809) in 2014.  Azithromycin resistant N. gonorrhoeae have been slowly increasing since 2011 when it was 0.4% (13/3,360) to 1.2% (37/3,195) in 2013. In 2014, the proportion increased to 3.3% (127/3,809).  The 2014 percentages of cefixime and ceftriaxone decreased susceptibility [1.1% (42/3,809) and 2.7% (101/3,809), respectively] are higher than they were in 2008 [0.5% (18/3,907) and 0.6% (24/3,907), respectively] but have decreased since 2011 [4.2% (140/3,360) and 6.2% (208/3,360), respectively].  Of the 6,706 viable isolates tested at NML between 2010 and 2014, none showed resistance to spectinomycin.

Figure 3. Trends of Antimicrobial Susceptibilities of Neisseria gonorrhoeae Tested in Canada, 2004-2014Figure 3 note a

Text description follows.
Description - Figure 3

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.

Antibiotic Year
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Penicillin Resistance 6.02% 9.42% 17.59% 13.94% 12.8% 18.7% 25.05% 22.2% 20.26% 18.94% 18.22%
Tetracycline Resistance 17.79% 20.92% 28.59% 22.88% 19.09% 24.7% 34.61% 29.4% 30.3% 32.99% 47.34%
Erythromycin Resistance 9.28% 12.54% 20.92% 24.89% 16.7% 21.3% 31.52% 26.6% 23.12% 24.32% 32.00%
Ciprofloxacin Resistance 6.25% 15.67% 29.42% 30.2% 21.96% 25.5% 35.93% 29.3% 28.52% 29.33% 34.02%
Azithromycin Resistance 0.15% 0.22% 0.19% 0.16% 0.13% 0.35% 1.25% 0.39% 0.86% 1.16% 3.33%
Cefixime Decreased Susceptibility 0.07% 0% 0.07% 0.09% 0.46% 1.19% 3.3% 4.2% 2.24% 1.75% 1.10%
Ceftriaxone Decreased Susceptibility 0% 0% 0.019% 0.42% 0.6% 3.12% 7.34% 6.2% 5.53% 3.51% 2.68%

Third Generation Cephalosporins

In 2014, the downward trend of isolates with decreased susceptibilities to cephalosporins continued.  According to WHO (2012) definitions (isolates with MICs ≥ 0.25 mg/L for cefixime and ≥ 0.125 mg/L for ceftriaxone have decreased susceptibility), 1.1% of isolates (42/3,809) were identified as having decreased susceptibility to cefixime and 2.7% (101/3,809) were identified as having decreased susceptibility to ceftriaxone (Figure 4).

In 2014, 3.1% of isolates (119/3,809) 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.

In 2010 and 2011, the modal MIC for cefixime was 0.125 mg/L.  This decreased to 0.032 mg/L In 2014. The ceftriaxone modal MIC has remained at 0.063 mg/L from 2010 thru 2013 but decreased to 0.032 mg/L in 2014 (Figures 7-10, Tables 8 and 9).

Figure 4. Neisseria gonorrhoeae Isolates Tested by the NML between 2010 and 2014 with Decreased Susceptibility to Cefixime and CeftriaxoneFigure 4 note a

Text description follows.
Description - Figure 4

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.

Antibiotic (MIC dilution) Year
2010 2011 2012 2013 2014
Cefixime (≥ 0.25 mg/L) 3.3% 4.2% 2.24% 1.75% 1.10%
Ceftriaxone (≥ 0.125 mg/L) 7.34% 6.2% 5.53% 3.51% 2.68%

Figure 5. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2010 to 2014Figure 5 note a

Text description follows.
Description - Figure 5

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.

Province Year
2010 2011 2012 2013 2014
Quebec 0.55% 2.20% 0.95% 0.56% 1.42%
Ontario 1.54% 7.18% 3.78% 2.78% 0.51%
Manitoba 0.00% 3.23% 0.00% 0.00% 2.17%
Alberta 3.89% 0.88% 0.80% 0.97% 3.85%
British Columbia 18.71% 4.08% 2.42% 1.54% 0.20%
Nova Scotia 0.00% 6.49% 0.00% 0.00% 0.00%
Saskatchewan 0.00% 0.00% 1.75% 1.45% 0.00%
Total No. of isolates 98 10 68 56 42
Table 6. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Cefixime, 2010 to 2014Table 6 note a
Province Year
2010 2011 2012 2013 2014
Quebec 6 23 8 4 13
Ontario 17 87 46 39 9
Manitoba 0 1 0 0 1
Alberta 11 4 4 5 18
British Columbia 64 20 9 7 1
Nova Scotia 0 5 0 0 0
Saskatchewan 0 0 1 1 0
Total No. of isolates 98 140 68 56 42
% CeDS of all isolates tested nationally 3.3% 4.2% 2.2% 1.8% 1.1%

Figure 6. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2010 to 2014Figure 6 note a

Text description follows.
Description - Figure 6

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.

Province Year
2010 2011 2012 2013 2014
Quebec 2.45% 1.72% 4.18% 1.26% 8.40%
Ontario 6.36% 11.14% 8.95% 5.77% 0.68%
Manitoba 0.00% 3.23% 2.04% 3.45% 2.17%
Alberta 6.36% 1.75% 1.61% 1.56% 2.35%
British Columbia 29.82% 8.57% 3.49% 2.86% 0.00%
Nova Scotia 0.00% 5.19% 0.00% 0.00% 0.00%
Saskatchewan 0.00% 0.00% 3.51% 0.00% 0.00%
Total No. of isolates 218 208 168 112 101
Table 7. Geographical Distribution of Neisseria gonorrhoeae Isolates with Decreased Susceptibility to Ceftriaxone, 2010 to 2014Table 7 note a
Province Year
2010 2011 2012 2013 2014
Quebec 27 18 35 9 77
Ontario 70 135 109 81 12
Manitoba 1 1 1 1 1
Alberta 18 8 8 8 11
British Columbia 102 42 13 13 0
Nova Scotia 0 4 0 0 0
Saskatchewan 0 0 2 0 0
Total No. of isolates 218 208 168 112 101
% CxDS of all isolates tested nationally 7.3% 6.2% 5.5% 3.5% 2.7%

Figure 7. Trends of Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 7 note a

Text description follows.
Description - Figure 7

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.

Year Dilutions (mg/L)
Susceptible Decreased Susceptibility
≤0.002 0.004 0.008 0.016 0.032 0.063 0.125 0.25 0.5
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%
2014
(N=2,101)
0.67% 2.81% 20.37% 16.90% 20.89% 19.42% 16.94% 1.81% 0.19%

Figure 8. Trends of Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 8 note a

Text description follows.
Description - Figure 8

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.

Year Dilutions (mg/L)
Susceptible Decreased Susceptibility
≤0.002 0.004 0.008 0.016 0.032 0.063 0.125 0.25
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%
2014
(N=2,101)
2.66% 13.09% 17.75% 11.57% 34.27% 15.85% 4.05% 0.76%

Figure 9. Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 9 note aFigure 9 note b

Text description follows.
Description - Figure 9

A stacked bar chart for cefixime.  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.

Dilutions (mg/L) Year
2010 2011 2012 2013 2014
0.032 mg/L Susceptible 21.5% 18.7% 23.1% 19.4% 20.9%
0.063 mg/L 10.0% 16.1% 18.2% 26.2% 19.4%
0.125 mg/L 28.1% 27.2% 21.2% 15.9% 16.9%
0.25 mg/L Decreased Susceptibility 8.0% 12.1% 6.6% 4.3% 1.8%
0.5 mg/L 0.0% 0.0% 0.0% 0.4% 0.2%
Table 8. Cefixime Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Table 8 note a
Dilutions
(mg/L)
Year
2010 2011 2012 2013 2014
0.063 mg/L 10.0% 16.1% 18.2% 26.2% 19.4%
0.125 mg/L 28.1% 27.2% 21.2% 15.9% 16.9%
0.25 mg/L 8.0% 12.1% 6.6% 4.3% 1.8%
0.5 mg/L 0.0% 0.0% 0.0% 0.4% 0.2%

Figure 10. Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 10 note aFigure 10 note b

Text description follows.
Description - Figure 10

A stacked bar chart 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.

Dilutions (mg/L) Year
2010 2011 2012 2013 2014
0.063 mg/L Susceptible 39.8% 35.3% 31.9% 28.9% 15.8%
0.125 mg/L Decreased Susceptibility 17.0% 17.2% 16.1% 9.3% 4.1%
0.25 mg/L 0.6% 0.8% 0.2% 0.2% 0.8%
Table 9. Ceftriaxone Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Table 9 note a
Dilutions
(mg/L)
Year
2010 2011 2012 2013 2014
0.063 mg/L 39.8% 35.3% 31.9% 28.9% 15.9%
0.125 mg/L 17.0% 17.2% 16.1% 9.3% 4.1%
0.25 mg/L 0.6% 0.8% 0.2% 0.2% 0.8%

Azithromycin

The distribution of azithromycin resistant isolates across Canada is represented in Figure 11 and Table 10.  Azithromycin resistant N. gonorrhoeae have been slowly increasing since 2011 when it was 0.4% (13/3,360) to 1.2% (37/3,195) in 2013. In 2014, the proportion increased to 3.3% (127/3,809), including 38 isolates from an outbreak (ST-10567). The proportion of azithromycin resistant isolates excluding the outbreak isolates is 2.3% (89/3,809).

The modal MIC for azithromycin remained at 0.5 mg/L between 2010 and 2012.  In 2013 and 2014, the modal MIC decreased to 0.25 mg/L (Figures 12 and 13 and Table 11).  Between 2009 and 2012, five isolates with high level azithromycin resistance (MIC ≥256 mg/L) were identified in Canada.

Figure 11. Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2010 to 2014Figure 11 note a

Text description follows.
Description - Figure 11

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.

Province Year
2010 2011 2012 2013 2014
Quebec 1.18% 0.67% 1.67% 1.54% 6.86%
Ontario 0.64% 0.08% 0.74% 0.85% 3.17%
Alberta 5.30% 0.22% 0.20% 0.78% 1.50%
British Columbia 0.58% 0.20% 0.54% 0.88% 0.20%
Nova Scotia 0.00% 1.30% 0.00% 0.00% 0.00%
Saskatchewan 0.00% 16.67% 0.00% 8.70% 0.00%
Total No. of AzR isolates 37 13 26 37 127
Table 10. Geographical Distribution of Azithromycin Resistant Neisseria gonorrhoeae Isolates, 2010 to 2014Table 10 note a
Province Year
2010 2011 2012 2013 2014
Quebec 13 7 14 11 63
Ontario 7 1 9 12 56
Alberta 15 1 1 4 7
British Columbia 2 1 2 4 1
Nova Scotia 0 1 0 0 0
Saskatchewan 0 2 0 6 6
Total No. of AzR isolates 37 13 26 37 127
% AzR of all isolates tested nationally 1.2% 0.4% 0.9% 1.2% 3.3%

Figure 12. Trends of Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 12 note aFigure 12 note b

Text description follows.
Description - Figure 12

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.

Year Dilution (mg/L)
Susceptible Resistant
0.125 0.25 0.5 1 ≥2
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%
2014 (N=2,101) 24.13% 30.99% 24.80% 6.76% 6.04%

Figure 13. Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 13 note aFigure 13 note b

Text description follows.
Description - Figure 13

A stacked bar chart with  each 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.

Dilution (mg/L) Year
2010 2011 2012 2013 2014
0.25 mg/L Susceptible 18.3% 23.3% 24.2% 36.2% 31.0%
0.5 mg/L 58.2% 56.1% 43.7% 33.9% 24.8%
1 mg/L 3.6% 5.2% 1.8% 2.5% 6.8%
≥2 mg/L Resistant 3.0% 1.1% 2.5% 3.1% 6.0%
Table 11. Azithromycin Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Table 11 note a
Dilution (mg/L) Year
2010 2011 2012 2013 2014
0.25 mg/L 18.3% 23.3% 24.2% 36.2% 31.0%
0.5 mg/L 58.2% 56.1% 43.7% 33.9% 24.8%
1 mg/L 3.6% 5.2% 1.8% 2.5% 6.8%
≥2 mg/L 3.0% 1.1% 2.5% 3.1% 6.0%

Co-Resistance - Azithromycin & Cephalosporins

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) and in 2014 only one (0.03%, 1/3,809) 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 possibly threatening the success of currently recommended dual therapy treatment options.

Table 12. Neisseria gonorrhoeae Isolates with Combined Decreased Susceptibility to Cephalosporins and Resistance to AzithromycinTable 12 note a
Year Number of AziR Isolates Percent AziRTable 12 note a Number of AziR Isolates with CeDS and/or CxDS Percent AziR Isolates with CeDS and/or CxDSTable 12 note a NG-MAST of AziR with CeDS and/or CxDS Provinces
2010 37 1.20% 2 0.07% ST-1407; ST-4980 ON (2)
2011 13 0.40% 0 0% N/A N/A
2012 26 0.90% 7 0.20% ST-3158 (6); ST-1407 (1) BC (1), ON (6)
2013 37 1.20% 8 0.30% ST-3158 (6); ST-1407 (1); ST-9427 (1) BC (2), SK (1), ON (5)
2014 127 3.30% 1 0.03% ST-1407 QC

Ciprofloxacin

The percentage of ciprofloxacin resistant isolates increased from 29.3% (937/3,195) in 2013 to 34.0% (1,296/3,809) in 2014.  Percentages for each province are represented in Figure 14 and Table 13.  Of the 1,296 ciprofloxacin resistant isolates identified in 2014, 96.8% (1,255/1,296) were also resistant to at least one other antibiotic; 34.5% (447/1,296) were characterized as CMRNG.

Figure 14. Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoeae Isolates, 2010 to 2014Figure 14 note a

Text description follows.
Description - Figure 14

A cluster bar chart showing the distribution of ciprofloxacin resistant Neisseria gonorrhoeae isolates throughout the provinces from 2010 to 2014.  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.

Province Year
2010 2011 2012 2013 2014
Quebec 26.64% 24.59% 41.41% 38.55% 36.82%
Ontario 32.70% 33.09% 29.23% 30.91% 39.05%
Manitoba 41.67% 32.26% 10.20% 13.79% 43.48%
Alberta 49.47% 28.88% 13.08% 16.15% 28.85%
British Columbia 71.05% 33.27% 22.04% 24.23% 20.73%
Nova Scotia 7.25% 22.08% 0.00% 0.00% 0.00%
New Brunswick 55.56% 0.00% 33.33% 60.00% 33.33%
Saskatchewan 25.71% 14.29% 15.79% 36.23% 9.89%
Newfoundland 42.86% 0.00% 0.00% 100.00% 11.11%
Prince Edward Island 0.00% 0.00% 100.00% 50.00% 0.00%
Total No. of CipR isolates 1,068 985 866 937 1,296
Table 13. Geographical Distribution of Ciprofloxacin Resistant Neisseria gonorrhoeae Isolates, 2010 to 2014Table 13 note a
Province Year
2010 2011 2012 2013 2014
Quebec 293 257 347 276 338
Ontario 360 401 356 434 690
Manitoba 10 10 5 4 20
Alberta 140 132 65 83 135
British Columbia 243 163 82 110 102
Nova Scotia 5 17 0 0 0
New Brunswick 5 0 1 3 1
Saskatchewan 9 5 9 25 9
Newfoundland 3 0 0 1 1
Prince Edward Island 0 0 1 1 0
Total No. of CipR isolates 1068 985 866 937 1,296
% CipR of all isolates tested nationally 36.0% 29.3% 28.5% 29.3% 34.0%

Figure 15. Trends of Ciprofloxacin Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2010 to 2014Figure 15 note a

Text description follows.
Description - Figure 15

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.

Year Dilution Range (mg/L)
Intermediate or Susceptible Resistant
≤ 0.25 0.5 1 2 4 8 16 ≥ 32
2010 (N=1,233) 12.57% 0.57% 0.73% 1.62% 14.60% 8.03% 58.64% 3.00%
2011 (N=1,158) 14.68% 0.26% 9.24% 2.59% 13.39% 9.84% 46.80% 3.20%
2012 (N=1,031) 15.32% 0.68% 6.60% 1.94% 15.91% 16.49% 41.51% 1.55%
2013 (N=1,183) 20.78% 0.00% 3.63% 2.37% 21.39% 22.74% 26.71% 2.36%
2014 (N=2,101) 38.18% 0.14% 0.76% 1.71% 12.71% 18.09% 27.61% 0.81%

Ertapenem

The NML began testing ertapenem in 2012.  In both 2013 and 2014, the ertapenem modal MIC was 0.063 mg/L (Figure 16).

Although there are no official MIC interpretative standards for N. gonorrhoeae for ertapenem,  Unemo (2009) suggests that an ertapenem MIC of 0.032 mg/L is susceptible (S),  and ertapenem MICs of 0.064 mg/L and 0.125 mg/L are not susceptible (NS).

Figure 16. Trends of Ertapenem Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2013 to 2014Figure 16 note a

Text description follows.
Description - Figure 16

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.

Year Dilution Range (mg/L)
Susceptible Not Susceptible
0.004 0.008 0.016 0.032 0.063 0.125 0.25 0.5
2013 (N=1,175) 0.00% 0.26% 1.45% 13.28% 36.26% 32.43% 15.40% 0.94%
2014 (N=2,101) 0.24% 0.57% 2.52% 23.75% 32.08% 23.70% 15.52% 1.57%

Gentamicin

The NML began testing gentamicin in 2012.  The gentamicin modal MIC for all isolates tested from 2013 to 2014 is 8 mg/L (Figure 17).

Although there are no official MIC interpretative standards for N. gonorrhoeae gentamicin, Brown (2010) used the following criteria for gentamicin: R >=32 mg/L, I from 8 to 16 mg/L and S<=4 mg/L based on the Daly (1997) study.

Figure 17. Trends of Gentamicin Susceptibilities of Neisseria gonorrhoeae Isolates Tested by the NML from 2013 to 2014Figure 17 note a

Text description follows.
Description - Figure 17

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.

Year Dilution Range (mg/L)
Susceptible Intermediate
2 4 8 16
2013 (N=1,183) 0.08% 4.90% 88.59% 6.42%
2014 (N=2,101) 0.33% 7.00% 90.15% 2.52%

Neisseria gonorrhoeae Multi-antigen Sequencing (NG-MAST)

NG-MAST molecular-based sequence typing provides a substantial level of discrimination between isolates.  In 2014, the most common sequence types (STs) identified by the NML wereST-2400 [14.1% (296/2,101)], ST-5985 [14.0% (294/2,101)] andST-10451 [9.8% (205/2,101)] (Figure 18).

Canadian isolates identified in 2014 that are highly related toST-2400 (Figure 24) include ST-6360 (n=28),ST-8115 (n=7),ST-8030 (n=6) plus 19 other STs with one to four isolates in each for a total of 371 or 17.7% of isolates in theST-2400 genogroup, (STs with tbpB-563 and por alleles within 2 nucleotide base pairs of the por allele ofST-2400).  Isolates of this genogroup are resistant to multiple drugs with 44.2% (164/371) and 28.6% (106/371) being Probable CMRNG and CMRNG, respectively.  All of these isolates are resistant to ciprofloxacin and 19.1% (71/371) have decreased susceptibility to cefixime and/or ceftriaxone.  Only 1.1% (4/371) are resistant to azithromycin (Figure 22).

ST-5985 increased in prevalence from 0.6% in 2012 to 6.1% in 2013 and then to 14.0% in 2014 (Figure 19).ST-10131 (n=15),ST-11348 (n=5) andST-10590 (n=2) plus 9 other single ST types differ fromST-5985 by only 1 base pair (Figure 24) for a total of 325 (15.5%) isolates in theST-5985 genogroup.   Isolates of this genogroup are primarily TRNGs [98.5% (320/325)] with 0.9% (3/325) being TRNG and resistant to another antibiotic.

ST-10451, the 3rd most prevalent ST in 2014 (9.8%), is only 1 base pair different thanST-1407 and isolates have similar antimicrobial resistance profiles (Figure 24).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 gonorrhea 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) and in 2014 only 2.2% (47/2,101) of isolates were identified asST-1407 (Figure 19). As mentioned previously,ST-10451 is highly related toST-1407, as isST-11765 (n=11),ST-6899 (n=8),ST-3158 (n=4) andST-3148 (n=3) plus 12 other STs with one to three isolates in 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 13.9% of isolates (293/2,101) were eitherST-1407 or highly related sub-types ofST-1407.  This percentage is slightly higher than 2013 (11.2%) but has decreased since 2012 which had 23.6% (243/1,031) of isolates within theST-1407 genogroup.  The isolates in 2014'sST-1407 genogroup are primarily CMRNG [68.3% (200/293)] and Probable CMRNG [27.6% (81/293)].  All are resistant to ciprofloxacin.   Only 2.4% (7/293) of isolates in thisST-1407 genogroup had decreased susceptibility to cefixime and/or ceftriaxone however, 18.8% (55/293) of them were resistant to azithromycin (Figure 22).

Distribution of STs within provinces is represented in Figures 20 and 21. ST-2400 was identified in 4 provinces including QC [48.3% (143/296)], ON [42.9% (127/296)], BC [5.1% (15/296)] and AB [3.7% (11/296)]. ST-5985, the next most prevalent ST type, was identified in BC [60.4% (177/293)], then ON [21.5% (63/293)], AB [14.7% (43/293)], SK [3.4% (10/293)] and MB [0.3% (1/293)]. ST-10451 was identified primarily in ON [96.6% (198/205)], then QC [2.9% (6/205)], and AB [0.5% (1/205)].

Figure 18. Prevalent NG-MAST Sequence Type Distribution of Neisseria gonorrhoeae Isolates Tested by the NML, 2014; N=2,101Figure 18 note a

Text description follows.
Description - Figure 18

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.

NG-MAST No. of isolates
ST-2400 296
ST-5985 294
ST-10451 205
ST-9663 134
ST-1407 47
ST-10567 39
ST-9523 39
ST-10452 35
ST-6360 29
ST-11299 26
ST-10129 23
ST-9665 20
ST-7638 19
ST-2992 17
ST-10131 15
ST-10132 15
ST-3935 14
ST-5624 14
ST-8502 13
ST-8684 13
ST-9551 13
ST-8695 12
ST-11765 11
ST-4637 11
ST-8890 11
ST-10450 10
ST-2318 10
ST-3150 10
ST-9999 10
ST-11086 9
ST-21 9
ST-25 9
ST-4995 9
ST-69 9
ST-9047 9
ST-5268 8

Figure 19. Trends of Prevalent NG-MAST Sequence Types of Neisseria gonorrhoeae Isolates Tested by NML, 2010 - 2014Figure 19 note a

Text description follows.
Description - Figure 19

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.

NG-MAST 2010
(N=1,233)
2011
(N=1,158)
2012
(N=1,031)
2013
(N=1,183)
2014
(N=2,101)
ST-2400 0.00% 0.43% 7.37% 12.09% 14.09%
ST-1407 13.22% 15.11% 11.06% 4.56% 2.24%
ST-5985 0.08% 0.00% 0.58% 6.09% 13.99%
ST-9663 0.00% 0.00% 0.00% 7.35% 6.38%
ST-10451 0.00% 0.00% 0.00% 0.85% 9.76%
ST-3307 1.30% 9.33% 5.72% 2.70% 0.38%
ST-3150 11.44% 1.30% 6.60% 2.87% 0.48%
ST-3550 5.19% 5.87% 5.14% 0.34% 0.00%
ST-3158 9.00% 3.80% 3.49% 1.61% 0.19%
ST-2992 2.43% 1.47% 2.13% 0.42% 0.81%
ST-3935 0.24% 2.16% 1.36% 0.68% 0.67%
ST-4709 0.32% 1.04% 1.94% 2.03% 0.14%
ST-7986 0.00% 0.60% 4.07% 0.76% 0.00%
ST-225 5.27% 2.42% 1.75% 0.17% 0.24%
ST-9523 0.00% 0.00% 0.00% 1.18% 1.86%
ST-4266 4.06% 3.28% 0.78% 0.00% 0.00%
ST-292 0.97% 1.47% 1.75% 0.42% 0.19%
ST-6360 0.00% 0.00% 0.19% 1.01% 1.38%
ST-10452 0.00% 0.00% 0.00% 0.34% 1.71%
ST-10567 0.00% 0.00% 0.00% 0.08% 1.86%
ST-5005 3.00% 3.11% 0.10% 0.00% 0.00%

Figure 20. Provincial Distribution within Neisseria gonorrhoeae NG-MAST Sequence Types, 2014; N=2,101Figure 20 note a

Text description follows.
Description - Figure 20

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.

NG-MAST Alberta British Columbia Manitoba New Brunswick Nova Scotia Newfoundland Ontario Quebec Saskatchewan
ST-2400 11 15         127 143  
ST-5985 43 177 1       63   10
ST-10451 1           198 6  
ST-9663 10 5 9 1     90 19  
ST-1407 3           15 29  
ST-10567 2         1   36  
ST-9523 1           38    
ST-10452             34 1  
ST-6360 3           7 19  
ST-11299 24 1         1    
ST-10129 20 1             2
ST-9665 1 16         3    
ST-7638 8             2 9
ST-2992 6 1 2     2     6
ST-10131 1 13         1    
ST-10132 8 1         2 4  
ST-3935 4 2             8
ST-5624 1 1         9 3  
ST-8502 6 6         1    
ST-8684 4 5         3 1  
ST-9551 12           1    
ST-8695   5 6           1
ST-11765             11    
ST-4637 10 1              
ST-8890   10             1
ST-10450             10    

Figure 21. Distribution of Neisseria gonorrhoeae NG-MAST Sequence Types within Provinces, 2014; N=2,101Figure 21 note a

Figure 21a. Distribution of NG-MAST within Alberta (N=339)
Text description follows.
Description - Figure 21a

Pie chart is divided into segments representing the proportion of specific NG-MAST sequence types found in that province.

NG-MAST Number
ST-5985 43
ST-11299 24
ST-10129 20
ST-9551 12
ST-2400 11
ST-4637 10
ST-9663 10
ST-9999 10
ST-10132 8
ST-25 8
ST-2992 8
ST-10838 6
ST-8502 6
Other 157
Figure 21b. Distribution of NG-MAST within British Columbia (N=336)
Text description follows.
Description - Figure 21b

Pie chart is divided into segments representing the proportion of specific NG-MAST sequence types found in that province.

NG-MAST Number
ST-5985 177
ST-9665 16
ST- 2400 15
ST-10131 13
ST-8890 10
ST-10532 8
ST-8502 6
ST-8684 5
ST-8695 5
ST-9663 5
ST-11560 4
Other 72
Figure 21c. Distribution of NG-MAST within Saskatchewan (N=91)
Text description follows.
Description - Figure 21c

Pie chart is divided into segments representing the proportion of specific NG-MAST sequence types found in that province.

NG-MAST Number
ST-5985 10
ST-7638 9
ST-210 8
ST-3935 8
ST-2992 6
ST-11348 4
ST-292 4
ST-1109 3
ST-2 3
ST-3654 3
ST-4709 3
Other 30
Figure 21d. Distribution of NG-MAST within Ontario (N=855)
Text description follows.
Description - Figure 21d

Pie chart is divided into segments representing the proportion of specific NG-MAST sequence types found in that province.

NG-MAST Number
ST-10451 198
ST-2400 127
ST-9663 90
ST-5985 63
ST-9523 38
ST-10452 35
ST-1407 15
ST-11765 11
ST-10450 10
ST-5624 9
ST-69 9
Other 250
Figure 21e. Distribution of NG-MAST within Quebec (N=408)
Text description follows.
Description - Figure 21e

Pie chart is divided into segments representing the proportion of specific NG-MAST sequence types found in that province.

NG-MAST Number
ST-2400 143
ST-10567 36
ST-1407 29
ST-6360 19
ST-9663 19
ST-3150 10
ST-9047 9
ST-9994 8
ST-10451 6
ST-9991 6
Other 123

Figure 22. Distribution of Resistance Characterizations within Neisseria gonorrhoeae NG-MAST Sequence Types, 2014; N=2,101Figure 22 note a

Text description follows.
Description - Figure 22

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.

NG-MAST EryR &/or TetR & AziR/EryR & AziR/EryR/TetR CxDS/CipR & CxDS/CipR/TetR & CeDS/CxDS/CipR/TetR CipR & CipR/EryR/TetR & CipR/EryR & CipR/TetR & CipR/PenR & CipR/PenR/TetR & EryR/TetR PPNGs with other antibiotic resistances including CMRNG PPNG/TRNG & PPNG/TRNG/EryR & TRNG/CMRNG TRNG & TRNG/CipR/PenR & TRNG/EryR Probable CMRNG/CipR & Probable CMRNG/AziR Probable CMRNG/CxDS/CipR or Probable CMRNG/CeDS/CxDS/CipR CMRNG/AziR/CipR & CMRNG/CipR CMRNG/CipR with or without AziR but with CeDS and/or CxDS Susceptible Total
ST-2400   3 63       126 3 37 64   296
ST-5985 1         293           294
ST-10451     4       50   151     205
ST-9663     97       30   7     134
ST-1407     4       22   17 4   47
ST-10567 38                   1 39
ST-9523         39             39
ST-10452     24       10   1     35
ST-6360     22       7         29
ST-11299             3   19 4   26
ST-10129 3                   20 23
ST-9665         20             20
ST-7638 7           1       11 19
ST-2992 13                   4 17
ST-10131           15           15
ST-10132     3       10   2     15
ST-3935 13           1         14
ST-5624   7   7               14
ST-8502                 13     13
ST-8684         5 8           13
ST-9551   12           1       13
ST-8695             1   11     12
ST-11765             3   8     11
ST-4637                     11 11
ST-8890 11                     11
ST-10450     6       3   1     10
ST-2318             4   6     10
ST-3150     3           7     10
ST-9999     8       2         10

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-9551 [30.2% (13/42)] followed by ST-11299, ST-1407 and ST-2400 [9.3% (4/42)] (Figure 23a).

Isolates with decreased susceptibility to ceftriaxone were primarily ST-2400 [68.6% (70/102)] with ST-9551 [3.9% (4/102)] following (Figure 23b).

The ST types identified among the AziR isolates are displayed in Figure 23c.  ST-10451 [31.5% (40/127)] and ST-10567 [29.9% (38/127)] are the most prevalent.

The STs of the susceptible isolates available for testing included ST-10129 [13.7% (20/146)], ST-4637 [7.5% (11/146)] and ST-7638 [7.5% (11/146)] as well as many others (Figure 23d).

Figure 23. NG-MAST Sequence Types of 2014 Neisseria gonorrhoeae IsolatesFigure 23 note a

Figure 23a. Decreased Susceptibility to Cefixime (MIC ≥ 0.25 mg/L), N=42
Text description follows.
Description - Figure 23a
NG-MAST Percentage
ST-9551 (n=13) 30.2%
ST-11299 (n=4) 9.3%
ST-2400 (n=4) 9.3%
ST-1407 (n=3) 9.3%
ST-4822 (n=3) 7.0%
ST-5308 (n=3) 7.0%
ST-2958 (n=2) 4.7%
ST-10225 (n=1) 2.3%
ST-11417 (n=1) 2.3%
ST-11541 (n=1) 2.3%
Other (n=7) 16.3%
Total (n=42) 100.0%
Figure 23b. Decreased Susceptibility to Ceftriaxone (MIC ≥ 0.125 mg/L), N=101
Text description follows.
Description - Figure 23b
NG-MAST Percentage
ST-2400 (n=69) 67.6%
ST-9551 (n=4) 3.9%
ST-11299 (n=3) 2.9%
ST-4822 (n=3) 2.9%
ST-1407 (n=2) 2.0%
ST-2958 (n=2) 2.0%
ST-5308 (n=2) 2.0%
ST-10225 (n=1) 1.0%
ST-11305 (n=1) 1.0%
ST-11417 (n=1) 1.0%
Other (n=13) 12.7%
Total (n=101) 100.0%
Figure 23c. Azithromycin Resistant (MIC ≥ 2 mg/L), N=127
Text description follows.
Description - Figure 23c
NG-MAST Percentage
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=127) 100.0%
Figure 23d. SusceptibleFigure 23 note b Isolates, N=146
Text description follows.
Description - Figure 23d
NG-MAST Percentage
ST-10129 (n=20) 13.7%
ST-4637 (n=11) 7.5%
ST-7638 (n=11) 7.5%
ST-25 (n=8) 5.5%
ST-3671 (n=8) 5.5%
ST-10838 (n=7) 4.8%
ST-2 (n=6) 4.1%
ST-210 (n=6) 4.1%
ST-51 (n=6) 4.1%
ST-2992 (n=4) 2.7%
Other (n=59) 40.4%
Total (n=146) 100.0%

Figure 24. Genetic Relationship of Prevalent Neisseria gonorrhoeae NG-MAST Sequence Types, 2014Figure 24 note aFigure 24 note bFigure 24 note c

Text description follows.

The evolutionary history was inferred using the Neighbor-Joining method (Saitu, 1987). The optimal tree with the sum of branch length = 554.32211304 is shown. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the number of differences method (Nei, 2000) and are in the units of the number of base differences per sequence. The analysis involved 35 nucleotide sequences. Codon positions included were 1st+2nd+3rd+Noncoding. All positions containing gaps and missing data were eliminated. There were a total of 800 positions in the final dataset. Evolutionary analyses were conducted in MEGA6 (Tamura, 2013).

Description - Figure 24

The genetic relationship was inferred using the Neighbor-Joining method (Saitu, 1987). The optimal tree with the sum of branch length = 554.32211304 is shown. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the number of differences method (Nei, 2000) and are in the units of the number of base differences per sequence. The analysis involved 35 nucleotide sequences. Codon positions included were 1st+2nd+3rd+Noncoding. All positions containing gaps and missing data were eliminated. There were a total of 800 positions in the final dataset. Evolutionary analyses were conducted in MEGA6 (Tamura, 2013).

Plasmids

Plasmid profiles for PPNG, TRNG and PPNG/TRNG isolates are shown in Figure 25.  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 2014, the 3.2 Mda plasmid was the most common type amongst the 64 PPNG strains isolated at 67.2% (43/64), followed by the 3.05 Mda plasmid at 25.0% (16/64) and then the 4.5 Mda plasmid at 7.8% (5/64). 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 66.1% (72/109).  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 2014, 19.4% (81/417) had the 2.6 and 25.2 Mda plasmids. TRNG isolates accounted for 89.2% of all the plasmid mediated resistance in N. gonorrhoeae in 2014 (526/590 PPNG, PPNG/TRNG and TRNG strains).

Figure 25. Plasmid Distribution within Antimicrobial Classifications of Neisseria gonorrhoeae Isolates Received by the NML, 2014

Figure 25a. PPNG (N=64)
Text description follows.
Description - Figure 25a
Plasmid Profile Percentage
2.6 - 4.5 - 24.5 (n=3) 4.7%
2.6 - 3.05 - 24.5 (n=15) 23.4%
2.6 - 3.2 - 24.5 (n=18) 28.1%
2.6 - 3.2 (n=24) 37.5%
2.6 - 3.05 (n=1) 1.6%
2.8 - 3.2 (n=1) 1.6%
2.6 - 4.5 (n=1) 1.6%
4.5 (n=1) 1.6%
Figure 25b. PPNG/TRNG (N=109)
Text description follows.
Description - Figure 25b
Plasmid Profile Percentage
2.6 - 3.2 - 25.2 (n=71) 65.1%
2.6 - 4.5 - 25.2 (n=28) 25.7%
2.6 - 3.05 - 25.2 (n=6) 5.5%
4.5 - 25.2 (n=3) 2.8%
3.2 - 25.2 (n=1) 0.9%
Figure 25c. TRNG (N=417)
Text description follows.
Description - Figure 25c
Plasmid Profile Percentage
25.2 (n=333) 79.9%
2.6 - 25.2 (n=81) 19.4%
3.2 - 25.2 (n=2) 0.5%
2.6 - 3.2 - 25.2 (n=1) 0.2%

Conclusion

The evolution of antimicrobial resistance in gonorrhea 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 gonorrhea.  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 gonorrhea treatment changes.  In 2011, The Canadian STI Guidelines issued updated recommendations for the use of combination gonorrhea 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 gonorrhea 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 percentage decreased to 5.9% in 2012, 3.9% in 2013 and 3.1% in 2014.    Similarly, the US reported drops in decreased susceptibility to cefixime (1.4% in 2011 to 0.4% in 2013) and decreased susceptibility to ceftriaxone (0.4% in 2011 to 0.05% in 2013) (CDC, 2014).  The UK reported that the prevalence of isolates with decreased cefixime susceptibility dropped from 6.3% in 2010 to 1.3% in 2013 and decreased ceftriaxone susceptibility declined from 0.3% in 2009 to 0.1% in 2013  (Public Health England, 2014).

With the decline in decreased susceptibility to cephalosporins, however, there was an increase in resistance to azithromycin in Canada (3.3%). While this percentage included 38 isolates from an outbreak (ST-10567), the proportion of azithromycin resistant isolates excluding the outbreak isolates was still 2.3%.  This proportion of resistance approaches the 5% level at which an antimicrobial should be reviewed as an appropriate treatment, according to the WHO (2012).  Canadian azithromycin levels were higher than the US', which ranged from 0.2% to 0.6% between 2009 and 2013 (CDC, 2014), and the UK's (MIC ≥ 1 mg/L) which reported 1.6% in 2013 (Public Health England, 2014). Australia reported 2.1% azithromycin resistance among their isolates in 2013 (Lahra, 2015).

Enhancing surveillance to include linked epidemiological and laboratory data would address the limitations in the current passive surveillance system regarding data representativeness and interpretation. A pilot program, the Enhanced Surveillance of Antimicrobial Resistant Gonorrhea (ESAG) was initiated in 2014 and is being assessed to fill this gap.

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 gonorrhea.  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, 2010 - 2014Appendix A note a
Province 2010 GC Cultures 2011 GC Cultures 2012 GC Cultures 2013 GC Cultures 2014 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 342 256 74.90% 490 176 35.90% 372 92 24.70% 454 170 37.40% 492 336 68.29%
Alberta 283 164 58.00% 457 156 34.10% 497 94 18.90% 514 134 26.10% 468 339 72.44%
Saskatchewan 35 11 31.40% 35 35 100% 57 57 100% 69 67 97.10% 91 91 100.00%
Manitoba 24 11 45.80% 31 12 38.70% 49 8 16.30% 29 7 24.10% 46 46 100.00%
Ontario 1,101 383 34.80% 1,212 428 35.30% 1,218 403 33.10% 1404 498 35.50% 1767 855 48.39%
Québec 1,100 335 30.50% 1,045 282 27.00% 838 390 46.50% 716 298 41.60% 918 408 44.44%
New Brunswick 9 9 100% 12 6 50.00% 3 3 100% 5 5 100% 3 3 100.00%
Nova Scotia 69 69 100% 77 77 100% 0 0 n/a 1 1 100% 15 14 93.33%
Newfoundland 7 7 100% 1 0 0% 1 0 0% 1 1 100% 9 9 100.00%
Prince Edward Island 0 0 n/a 0 0 n/a 1 1 100% 2 2 100% 0 0 n/a
Totals 2,970 1,245 41.90% 3,360 1,172 34.90% 3,036 1,048 34.50% 3,195 1,183 37.00% 3,809 2,101 55.16%

Appendix B

Characterization of all Neisseria gonorrhoeae Isolates Submitted to the NML, 2010 - 2014
Characterization 2010 2011 2012 2013 2014 Totals
Plasmid Mediated Resistances PPNG/CipR 10 9 6 10 10 45
PPNG 6 2 3 3 17 31
PPNG/EryR 1 6 1 11 11 30
PPNG/EryR/CipR 1 0 2 0 2 5
PPNG/TetR 1 0 2 0 4 7
PPNG/TetR/CipR 1 1 4 4 8 18
PPNG/CMRNG/CipR 3 6 10 4 10 33
PPNG/CMRNG 0 2 2 4 2 10
PPNG/CMRNG/CxDS/CipR 0 1 0 0 0 1
PPNG/TRNG/CxDS/CipR/EryR 2 14 0 0 0 16
PPNG/TRNG/CeDS/CipR 0 2 0 0 0 2
PPNG/TRNG 0 2 11 18 36 67
PPNG/TRNG/AziR/CipR/EryR 1 0 0 1 0 2
PPNG/TRNG/CipR 32 43 49 43 46 213
PPNG/TRNG/CipR/EryR 7 33 22 34 20 116
PPNG/TRNG/CeDS/CxDS/CipR/EryR 0 3 0 0 0 3
PPNG/TRNG/CeDS/CipR/EryR 0 6 0 0 0 6
PPNG/TRNG/CxDS/CipR 0 0 0 1 1 2
PPNG/TRNG/EryR 0 0 0 3 6 9
TRNG 12 21 36 86 353 508
TRNG/CipR 22 15 16 29 21 103
TRNG/EryR 6 1 1 13 14 35
TRNG/CipR/EryR/CeDS 0 1 0 0 0 1
TRNG/CipR/CxDS 0 0 1 1 0 2
TRNG/CipR/EryR 11 36 47 42 17 153
TRNG/PenR 0 1 1 1 0 3
TRNG/CipR/EryR/CxDS 0 8 0 1 0 9
TRNG/CipR/PenR 0 1 0 2 2 5
TRNG/CxDS/CipR 0 1 0 0 0 1
TRNG/CipR/EryR/CeDS/CxDS 0 1 0 0 0 1
TRNG/CxDS 0 0 1 0 0 1
TRNG/CMRNG/CipR 1 2 2 4 9 18
TRNG/CMRNG 0 0 1 2 1 4
TRNG/CMRNG/CxDS/CipR 1 2 3 0 0 6
Total 118 220 221 317 590 1,466
Chromosome Mediated Resistances AziR/EryR/TetR 2 2 14 8 24 50
AziR/CeDS/CipR/EryR/TetR 0 0 0 1 0 1
AziR/EryR/PenR 0 1 0 0 0 1
AziR/EryR 21 5 0 3 32 61
AziR/CipR/EryR/TetR 0 0 0 2 3 5
CipR/TetR 26 23 56 71 103 279
CipR/EryR/TetR 15 9 4 34 176 238
CipR/EryR 10 16 3 2 15 46
CipR 54 33 44 51 41 223
CipR/PenR 0 0 0 2 2 4
CipR/PenR/TetR 0 0 2 2 0 4
EryR 0 8 3 3 9 23
EryR/TetR 3 28 10 13 30 84
PenR/TetR 0 0 0 2 4 6
PenR 0 0 0 1 0 1
TetR 9 18 22 8 56 113
CxDS/EryR 0 1 0 0 0 1
CeDS/CxDS/CipR/PenR/TetR 0 0 0 1 1 2
CeDS/CxDS/CipR/PenR 0 0 0 2 1 3
CeDS/CxDS/CipR 0 0 0 1 4 5
CxDS/CipR 1 1 0 2 1 5
CeDS/CipR/PenR 0 0 0 0 1 1
CeDS/CipR/EryR 1 0 0 0 0 1
CxDS/CipR/EryR/TetR 0 1 1 0 0 2
CeDS/CxDS/CipR/TetR 0 0 0 3 0 3
CxDS/CipR/TetR 1 0 3 2 0 6
CeDS/CxDS/CipR/EryR/TetR 0 0 0 0 3 3
CeDS/CipR/TetR 0 0 1 0 5 6
CeDS/CipR/EryR/TetR 0 0 0 0 1 1
CeDS/CipR 0 0 0 1 3 4
CeDS/CipR/PenR/TetR 0 1 0 0 0 1
CMRNG/CipR 443 386 294 295 305 1,723
CMRNG/AziR/CipR 8 5 5 7 46 71
CMRNG 3 2 4 26 41 76
CMRNG/AziR/CxDS/CipR 2 0 6 2 1 11
CMRNG/CxDS/CipR 104 80 92 43 70 389
CMRNG/CeDS/CxDS/CipR 79 88 55 30 11 263
CMRNG/AziR/CeDS/CxDS/CipR 0 0 1 4 0 5
CMRNG/CeDS/CipR 8 32 7 6 5 58
CMRNG/AziR 1 0 0 4 0 5
CMRNG/CxDS 0 0 0 0 1 1
CMRNG/AziR/CeDS/CipR 0 0 0 1 0 1
Probable CMRNG/CipR 194 110 123 175 326 928
Probable CMRNG/CeDS/CipR 0 5 2 1 4 12
Probable CMRNG/CxDS/CipR 17 6 4 14 3 44
Probable CMRNG/AziR 0 0 0 1 6 7
Probable CMRNG 4 2 9 6 12 33
Probable CMRNG/CeDS/CxDS/CipR 10 1 1 5 4 21
Probable CMRNG/AziR/CipR 2 0 0 2 15 19
Probable CMRNG/CeDS 0 0 1 0 0 1
Susceptible Strain 96 87 46 30 146 405
Total 1,119 952 818 868 1,511 5,268
 Other No Growth/Contaminated 12 13 11 4 15 55
Total 1,249 1,185 1,050 1,189 2,116 6,789

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.
  • Brown LB, Krysiak R, Kamanga G, Mapanje C, Kanyamula H, Banda B, Mhango C, Hoffman M, Kamwendo D, Hobbs M, Hosseinipour M, Martinson F, Cohen MS, Hoffman IF.  Neisseria gonorrhoeae antimicrobial susceptibility in Lilongwe, Malawi, 2007.  Sex Transm Dis 2010;37:169-172
  • 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/std/GISP2007/.
  • Centers for Disease Control and Prevention (CDC). Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012; 61:590-594.
  • 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/.
  • Centers for Disease Control and Prevention.  2013 Sexually Transmitted Diseases Surveillance. 2014.  Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.  Available: http://www.cdc.gov/std/stats13/gonorrhea.htm
  • 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-Fifth Informational Supplement M100-S25.  Clinical and Laboratory Standards Institute. Wayne, PA, 2015.
  • Daly CC, Hoffman I, Hobbs M, Maida M, Zimba D, Davis R, Mughogho G, Cohen MS. Development of an antimicrobial susceptibility surveillance system for Neisseria gonorrhoeae in Malawi:  Comparison of methods. J Clin Micro 1997;35:2985-2988.
  • 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.
  • Lahra MM.  Australian Gonococcal Surveillance Programme Annual Report, 2013. Commun Dis Intell. 2015;38:E137.
  • 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.
  • Nei M, Kumar S. Molecular Evolution and Phylogenetics. 2000. Oxford University Press, New York.
  • 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.2015. Notifiable Diseases On-Line. http://dsol-smed.phac-aspc.gc.ca/dsol-smed/ndis/charts.php?c=pl Accessed: 01 Sept 2015.
  • Public Health England.  GRASP 2013 report; The Gonococcal Resistance to Antimicrobial Surveillance Programme (England and Wales). 2014.2014442:1.
  • Saitou N, Nei M. The neighbor-joining method:  A new method for reconstructing phylogenetic trees.  Mol Biol Evol 1987;4:406-425.
  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6:  Molecular Evolutionary Genetics Analysis version 6.0.  Mol Biol Evol 2013;30:2725-2729.
  • 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, Fasth O, Fredlund H, Limnios A, Tapsall J.  Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes.  J Antimicrob Chemother  2009;63:1142-1151.
  • 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.
Date modified: