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Edward W. Hook, III, M.D. Professor, Medicine, Microbiology and Epidemiology University of Alabama at Birmingham

Challenges to IPP:   Emerging Gonococcal Antimicrobial Resistance and Skepticism That Screening in Its Current Form Can Reduce Chlamydial Morbidity. Edward W. Hook, III, M.D. Professor, Medicine, Microbiology and Epidemiology University of Alabama at Birmingham.

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Edward W. Hook, III, M.D. Professor, Medicine, Microbiology and Epidemiology University of Alabama at Birmingham

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  1. Challenges to IPP:  Emerging Gonococcal Antimicrobial Resistance and Skepticism That Screening in Its Current Form Can Reduce Chlamydial Morbidity Edward W. Hook, III, M.D. Professor, Medicine, Microbiology and Epidemiology University of Alabama at Birmingham

  2. Emerging Gonococcal Antimicrobial Resistance

  3. Emerging Gonococcal Antimicrobial Resistance – Deja Vu Pre-1937 Antiseptic Irrigation With Potassium Permanganate, Silver Salts, Mercurochrome 1937 Sulfonamide Therapy 1943 Penicillin Therapy (Mahoney et al) 1944 35%Treatment Failure With Sulfonamides 1972 Penicillin Regimen Increased to 4.8 Million Units Plus Probenecid

  4. Emerging Gonococcal Antimicrobial Resistance – Deja Vu 1976 Recognition of PPNG (AFRICA, S.E. ASIA) 1984 High Level Chromosomal Penicillin Resistance, (Durham, N.C.) 1985 Recognition of Plasmid Mediated Tetracycline Resistance 1987 High Level Spectinomycin Resistance, (Korea) 1989 Penicillin No Longer Drug of Choice for G.C. 2002 Concern Regarding Rising Quinolone MICs

  5. Gonococcal Isolate Surveillance Project (GISP) — Location of participating clinics and regional laboratories: United States

  6. Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001–2006

  7. Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990–2008 Note: Resistant isolates have ciprofloxacin MICs ≥1 µg/ml. Isolates with intermediate resistance have ciprofloxacin MICs of 0.125 - 0.5 µg/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990.

  8. 200610 CDC STD TREATMENT GUIDELINESUncomplicated Gonorrhea • Ceftriaxone 250 125 mg IM • or • Cefixime 400 mg PO • or • Ciprofloxacin 500 mg PO* • or • Ofloxacin 400 mg PO* • or • Levofloxacin 250 mg PO* • Plus, IF CHLAMYDIAL INFECTION IS NOT RULED OUT • Azithromycin 1.0 g Single Dose Or Doxycycline100 BID x 7d

  9. 2010 CDC STD TREATMENT GUIDELINESUncomplicated Gonorrhea • Ceftriaxone 250 mg IM • or • Cefixime 400 mg PO • PLUS • Azithromycin 1.0 g Single Dose or Doxycycline 100 BID x 7d

  10. "Those who cannot remember the past are condemned to repeat it." George Santayana

  11. Decreased Cephalosporin Susceptibility 1999 Japan: 0% isolates have MICs to cefixime ≥ 0.5 μg/ml 2001 Japan: Possible treatment failure with cefdinir 2002 Japan: 30% isolates have MICs to cefixime ≥ 0.5 μg/ml Japan: 8 (12%) of men with GC in study unsuccessfully treated with cefixime 2003 2007 Hong Kong: 4 treatment failures with cefixime • Increasing MICs to cephalosporins reported in Australia, Europe, and US • Japan: isolate with Ceftriaxone MIC of 2 µg/ml (female CSW) 2008-2009 2010 Norway: 2 treatment failures with cefixime Sweden: 1 pharyngeal GC treatment failure with ceftriaxone 250 mg

  12. Distribution of MICs to Cefixime, 2005–2010* Percentage of isolates Minimum Inhibitory Concentrations (MICs), µg/ml * Preliminary (Jan-Sept)

  13. Distribution of MICs to Cefixime, 2005–2010* Percentage of isolates 1.3% (n=58) 0.2% (n=8) Minimum Inhibitory Concentrations (MICs), µg/ml * Preliminary (Jan-Sept)

  14. Proportion of GISP isolates with MICs to Cefixime ≥ 0.25 μg/ml, 2000–2010* 1.5% (n=66) Cefixime AST not conducted Percentage of isolates * Preliminary (Jan-Sept)

  15. Proportion of GISP isolates with MICs to Cefixime ≥ 0.25 μg/ml by Region, 2000–2010* West 3.7% (n=57) Cefixime AST not conducted Percentage of isolates Midwest N’east & South * Preliminary (Jan-Sept)

  16. Proportion of GISP isolates with MICs to Cefixime ≥ 0.25 μg/ml by Sex of Sex Partner, 2000–2010* MSM Cefixime AST not conducted 4.7% (n=56) Percentage of isolates MSW * Preliminary (Jan-Sept)

  17. Distribution of MICs to Ceftriaxone, 2006–2010* Percentage of isolates Minimum Inhibitory Concentrations (MICs), µg/ml * Preliminary (Jan-Sept)

  18. Distribution of MICs to Ceftriaxone, 2006–2010* Percentage of isolates Minimum Inhibitory Concentrations (MICs), µg/ml * Preliminary (Jan-Sept) Pre

  19. Gonorrhea — Rates by state: United States and outlying areas, 2008 Note: The total rate of gonorrhea for the United States and outlying areas (Guam, Puerto Rico, and Virgin Islands) was 110.3 per 100,000 population.

  20. Emerging Resistance of C. trachomatis to Azithromycin, 2010?? • Cured (%)/ Treated • Doxycycline +/- 55 (95%)/58 • Tinidazole • Azithromycin +/- 41 (77%)/53 • Tinidazole • p= 0.01 Schwebke JS et al. CIC 2011;52: 163-170

  21. Skepticism That Screening in Its Current Form Can Reduce Chlamydial Morbidity Or Is IPP Working and Why Are U.S. Chlamydial Rates Increasing

  22. IPP Logic Model 1. Association of CT and GC with PID 2. Association of tubal factor infertility with PID 3. Evidence that CT screening reduces PID

  23. IPP Logic Model- Arguments 1. Association of CT and GC with PID Old data, association of other organisms (anaerobes, M. genitalium) with PID 2. Association of tubal factor infertility with PID 3. Evidence that CT screening reduces PID

  24. Etiologic Agents of Pelvic Inflamatory Disease 1. Neisseria Gonorrhoeae 2. Chlamydia trachomatis 3. Mycoplasma genitalium (proposed) 4. Anaerobic Bacteria 5. Non-STD pathogens Actinomycosis Mycobacterium tuberculosis Other

  25. IPP Logic Model- Arguments 1. Association of CT and GC with PID Old data, association of other organisms (anaerobes, M. genitalium) with PID 2. Association of tubal factor infertility with PID Declining PID rates, increasing CT rates 3. Evidence that CT screening reduces PID

  26. Sources of Imprecision in PID Diagnosis 1. Non-specificity of clinical PID diagnosis 2. Decreasing emphasis on hospitalization for PID management 3. Declining gonorrhea rates – milder PID signs an symptoms?

  27. Sensitivity Lower Abdominal Pain 94% Adnexal Tenderness 92% Increased Vaginal D/C 55% Fever > 38° 41% Specificity Laporoscopic Confirmation in 529/814 (65%) Clinically Diagnosed Cases Pelvic Inflammatory Disease:Accuracy of Clinical Diagnosis

  28. Prevention of Pelvic Inflammatory Disease by Screening for Chlamydia 2607 at risk women randomized to screening (N=1009) or usual care (N=1598) 645 (64%) were screened of whom 44 (7%) were infected and treated Pelvic Inflammatory Disease Incidence Screening 9/1009 (8 per 10,000 women months) Usual Care 33/1598 (18 per 10,000 women months) Relative Risk for Screening Group = 0.44 Scholes D, et al. NEJM 1996;334-1362-6.

  29. IPP Logic Model- Arguments 1. Association of CT and GC with PID Old data, association of other organisms (anaerobes, M. genitalium) with PID 2. Association of tubal factor infertility with PID Declining PID rates, increasing CT rates 3. Evidence that CT screening reduces PID Studies conducted in high risk women generalized to general population; occurrence of PID in women following screening

  30. U.S. Chlamydial Prevalence (NHANES), 14-39 YO Women, 1999-2008 Data From Johnson and Bermanin Modern Infectious Disease Epidemiology, Kraemer and Kretzschmar Eds. 2010

  31. IPP Logic Model- Arguments 1. Association of CT and GC with PID Old data, association of other organisms (anaerobes, M. genitalium) with PID 2. Association of tubal factor infertility with PID Declining PID rates, increasing CT rates 3. Evidence that CT screening reduces PID Studies conducted in high risk women generalized to general population; occurrence of PID in women following screening

  32. Suggested Steps To Enhance IPP 1. Measure PID and infertility, the outcomes of interest. 2. Efforts to expand testing 3. Consider new metrics to encourage continuous quality improvement (CQI)

  33. Accelerating Infertility Prevention With Small Steps:  CQI – Doing It Better Optimizing Chlamydia Screening Targeting those who need screening Improving the process of chlamydial screening Assuring Timely Treatment

  34. No Treatment Within 30 Days Treatment Within 13 Days of Screening Treatment Within 14-30 Days of Screening Time To Treatment Following STD Screening, JCHD STD Clinic 18% 20% 28% 35% 45% 54%

  35. Chlamydial Culture Performance in Women Without Other Indications for Therapy Patients with positive screening cultures 81 Patients referred elsewhere for therapy 3 Patients without documented F/U or therapy 20/78 (26%) PID at F/U 2/58 (4%) Interval to treatment (N=58) 7 days 24% 14 days 50% 21 days 60% 28 days 81% Hook et al. JAMA 1994; 272; 867-70

  36. Pelvic Inflammatory Incidence Following STD Screening • Baltimore STD Clinic – 2 (4%) of 58 • UAB Emergency Dept.- 3 (4.5%) of 67 • Birmingham STD Clinic – 2 (2%) of 115 Hook et al. JAMA 1994; 272: 867-70. Bachmann et al. .Sex Transm Dis. 1999;26(9):496-499. Geisler et al. Sex Trans Dis. 2008

  37. Improving Chlamydial Screening Through CQI: Potential Metrics Optimization of time from screening to treatment -Specimen transit time to lab -TAT in the lab -Time to recording of test results -Time to notification of infected persons -Mechanisms for facilitating treatment of persons with positive screening tests Evaluation and characterization of those who either do not get test results or fail to return

  38. Improving Chlamydial Screening Through CQI: Potential Metrics Infections diagnosed treated Time from screening to treatment Asymptomatic persons returning for re-screening at 6 months

  39. APTIMA Combo 2 Sensitivity

  40. Changing Paradigms For Urogenital Specimen Collection Pre-NAAT’s: Specimen Quality Critical - Endocervical Or Urethral Swabs - Swab Order Impacts Test Results : Culture > Non-Amplified Nucleic Acid Detection > Antigen Detection NAAT’s: More Forgiving Specimen Collection - Vaginal Swab = Endocervical Swab > Endocervical Swab > Initial Void Urine

  41. Arguments For Non-Invasive STD Testing Patient: Faster : Less Uncomfortable Provider: Faster : Fewer Resources Personnel Specula Examination Table System: Testing At Sites Of Opportunity : Patient Satisfaction

  42. Populations for Whom Non-Invasive STD Testing Have Been Used Non-Health Care Settings School Based Clinics Incarcerated Youth and Adults Military Recruits Homeless Persons - Street Outreach - Shelters Long Haul Truck Drivers

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