1. Review and Discussion of Gonococcal Isolate Surveillance Project (GISP) Data
Lizzi Torrone, MSPH, PhD
Lead, Surveillance & Special Studies Team
GISP Project Officer (acting)
Division of STD Prevention
SSS STAR STI Clinical Trials Group
April 13, 2017

2. Caveats Not Bob Kirkcaldy, but he is here
Presenting 2016 data which are preliminary—the numbers will change! Please do not distribute.

3. Gonococcal Isolate Surveillance Program (GISP)
Established in 1986 to monitor trends in N. gonorrhoeae susceptibility to antimicrobials
Collaboration between CDC, clinical sites, and laboratories
Directly inform CDC STD Treatment Guidelines
Data disseminated through routine surveillance reports

4. GISP isolate + data collection
27 participating STD clinics
Urethral specimens and epi data obtained from first 25 men with gonococcal urethritis at clinical sites each month
Isolates are sent to regional laboratories
Susceptibility testing conducted by agar dilution
Results provided to clinical sites (not for clinical decision making)
Epi and susceptibility data transmitted to CDC and merged for analysis
Alert isolates and archive isolates sent to CDC

5. Current GISP clinical sites
Phoenix
Albuquerque
Dallas
San Diego
Orange Co.
Las
Vegas
Portland
New
Orleans
Honolulu
San Francisco
Minneapolis
Philadelphia
Columbus
Chicago
Erie Co.
Boston
Atlanta
Birmingham
Seattle
Cleveland
Tripler AMC
Los Angeles
Greensboro
Pontiacit
New York
City
Kansas
Indianapolis

6. Antibiotic Resistance Lab Network (ARLN)

7. Gonorrhea trends in the U.S.

8. Gonorrhea — Rates of Reported Cases by Year, United States, 1941–2015
Rate per 100,000
1976: 1,013,436 cases
2010: 309,341 cases
2015: 395,216 cases
*2016 data are preliminary as of 4/3/17

9. Gonorrhea — Rates of Reported Cases by Year, United States, 1941–2016*
Rate per 100,000
1976: 1,013,436 cases
2016: 454,235 cases
15% increase
2010: 309,341 cases
2015: 395,216 cases
*2016 data are preliminary as of 4/7/17

10. Gonorrhea — Rates of Reported Cases by Sex, United States, 2006–2015
Rate per 100,000
Males
Females

11. Gonorrhea — Rates of Reported Cases by Sex, United States, 2006–2016*
Rate per 100,000
19% increase
Males
Females
10% increase
*2016 data are preliminary as of 4/7/17

12. Estimated Proportion* of MSM†, MSW†, and Women Among Gonorrhea Cases by Jurisdiction, STD Surveillance Network (SSuN), 2015
* Estimate based on weighted analysis of data obtained from interviews (n=2,278) conducted among a random sample of reported gonorrhea cases during June to December 2015.
† MSM = Gay, bisexual, and other men who have sex with men (collectively referred to as MSM); MSW = Men who have sex with women only.
‡ California data excludes San Francisco (shown separately).

13. Proportion of MSM* Attending STD Clinics with Primary and Secondary Syphilis, Gonorrhea (GC) or Chlamydia (CT) by HIV Status†, STD Surveillance Network (SSuN), 2015
* MSM = Gay, bisexual, and other men who have sex with men (collectively referred to as MSM).
† Excludes all persons for whom there was no laboratory documentation or self-report of HIV status.
‡ GC urethral and CT urethral include results from both urethral and urine specimens.

14. Proportion of MSM* Attending STD Clinics with Primary and Secondary Syphilis, Gonorrhea (GC) or Chlamydia (CT) by HIV Status†, STD Surveillance Network (SSuN), 2015
* MSM = Gay, bisexual, and other men who have sex with men (collectively referred to as MSM).
† Excludes all persons for whom there was no laboratory documentation or self-report of HIV status.
‡ GC urethral and CT urethral include results from both urethral and urine specimens.

15. Gonorrhea: Estimated burden & cost
395,000 cases diagnosed and reported in 2015
Most diagnosed outside of the STD clinic
Case reports underestimate burden of disease
~820,000 infections occur annually
Estimated $162 million in direct medical costs

16. GISP trends

17. Susceptibility criteria
Antimicrobial
Susceptibility criteria
Ceftriaxone
≥0.125 μg/ml
Elevated MICs
Cefixime
≥0.25 μg/ml
Azithromycin
≥2.0 μg/ml
Reduced susceptibility
Ciprofloxacin
≥1.0 μg/ml
Resistance
Penicillin
≥2.0 μg/ml or
Beta lactamase +
Tetracycline
Gentamicin
Not established

18. Neisseria gonorrhoeae — Distribution of Isolates with Penicillin, Tetracycline, and/or Ciprofloxacin Resistance, Gonococcal Isolate Surveillance Project (GISP), 2016*
Data are preliminary as of 4/9/2017; NOTE: PenR = penicillinase-producing Neisseria gonorrhoeae and chromosomally-mediated penicillin-resistant N. gonorrhoeae; TetR = chromosomally- and plasmid-mediated tetracycline-resistant N. gonorrhoeae; and QRNG = quinolone-resistant N. gonorrhoeae.

19. Neisseria gonorrhoeae — Percentage of Isolates with Elevated Cefixime MICs and Elevated Ceftriaxone MICs, GISP, 2006–2016*
Percentage
* 2016 data are preliminary as of 4/9/2017; Isolates not tested for cefixime susceptibility in 2007 and 2008.

20. Neisseria gonorrhoeae — Percentage of Isolates with Elevated Cefixime MICs and Elevated Ceftriaxone MICs, GISP, 2006–2016*
Percentage
0.25 μg/ml (n=17)
0.50 μg/ml (n=2)
0.125 μg/ml (n=18)
* 2016 data are preliminary as of 4/9/2017; Isolates not tested for cefixime susceptibility in 2007 and 2008.

21. Neisseria gonorrhoeae — Percentage of Isolates with Elevated Cefixime MICs and Elevated Ceftriaxone MICs, GISP, 2006–2016*
Percentage
* 2016 data are preliminary as of 4/9/2017; Isolates not tested for cefixime susceptibility in 2007 and 2008.

22. Neisseria gonorrhoeae — Percentage of Isolates with Elevated Cefixime MICs, Elevated Ceftriaxone MICs, and Azithromycin Reduced Susceptibility, GISP, 2006–2013
Percentage
*Isolates not tested for cefixime susceptibility in 2007 and 2008.

23. Neisseria gonorrhoeae — Percentage of Isolates with Elevated Cefixime MICs, Elevated Ceftriaxone MICs, and Azithromycin Reduced Susceptibility, GISP, 2006–2013
Percentage
* 2016 data are preliminary as of 4/9/2017; Isolates not tested for cefixime susceptibility in 2007 and 2008.

24. Neisseria gonorrhoeae — Distribution of Isolates with Azithromycin Reduced Susceptibility by MIC and by Year, GISP, 2011–2016*
Percentage
MICs (μg/ml)
* 2016 data are preliminary as of 4/9/2017

25. Percentage of Isolates with (A) Reduced Azithromycin Susceptibility and (B) Reduced Ceftriaxone Susceptibility with Other Resistance Phenotypes, 2015 A
Azithromycin-RS† (n=133) B
Ceftriaxone-RS† (n=14)
Percentage
† Azithromycin-RS=reduced azithromycin susceptibility (MIC ≥2 µg/ml); ceftriaxone-RS=reduced ceftriaxone susceptibility (MIC ≥0.125 µg/ml)
NOTE: Resistance categories are not mutually exclusive

26. Percentage of Isolates with (A) Reduced Azithromycin Susceptibility and (B) Reduced Ceftriaxone Susceptibility with Other Resistance Phenotypes, 2016* A
Azithromycin-RS† (n=200)
4 isolates
from Hawaii B
Ceftriaxone-RS† (n=18)
Percentage
† Azithromycin-RS=reduced azithromycin susceptibility (MIC ≥2 µg/ml); ceftriaxone-RS=reduced ceftriaxone susceptibility (MIC ≥0.125 µg/ml)
2016 data are preliminary as of 4/7/17; NOTE: Resistance categories are not mutually exclusive

27. Cluster of N. gonorrhoeae isolates with high-level azithromycin resistance AND reduced ceftriaxone susceptibility, April–May, 2016
High-level azithromycin resistance (MIC ≥256 µg/ml) in 8 specimens from 7 patients
4 isolates had reduced ceftriaxone susceptibility (MIC ≥0.125 µg/ml)
All were resistant to penicillin, tetracycline, & ciprofloxacin
Closely related by genomic analysis
All cases and 4/9 partners interviewed
All had sx resolution or tested negative
Katz A et al. STD Prevention Conference, 2016

28. Neisseria gonorrhoeae — Distribution of Gentamicin MICs by Year, GISP, 2015–2016*
Percentage
MICs (μg/ml)
* 2015 and 2016 data are preliminary as of 4/9/2017

29. (REALLY REALLY) preliminary 2017 data
Only 648 isolates with AST data to CDC
Similar patterns as 2016
To date:
No isolates with reduced susceptibility to both AZI and CRO
No isolates with CRO MIC >0.125 μg/ml
3 isolates with CFX MICs ≥0.25 μg/ml

31. Emergence of ceftriaxone-resistant N
Emergence of ceftriaxone-resistant N. gonorrhoeae could impose direct medical costs of over $400 million over the next 10 years.

32. Conclusions GISP in the CARB era GISP is not going away!
Continue to inform treatment guidelines

33. Conclusions GISP in the CARB era GISP is not going away!
Continue to inform treatment guidelines
eGISP funding

34. Conclusions (cont) Resistance is urgent threat
Dual therapy still highly effective
Declining cephalosporin and azithromycin susceptibility threatens last recommended gonorrhea treatment
New antimicrobials & innovative prevention and control strategies are urgently needed

35. Acknowledgements Alesia Harvey Tremeka Sanders Bob Kirkcaldy John Papp
Ellen Kersh
Hillard Weinstock
GISP clinical sites and regional laboratories

36. Lizzi Torrone igf0@cdc.gov 404-639-8948
Thank you!
Lizzi Torrone

37. Neisseria gonorrhoeae — Distribution of Azithromycin MICs by Year, GISP, 2011–2016*
Percentage
MICs (μg/ml)
* 2016 data are preliminary as of 4/9/2017