Mycoplasma genitalium:

Transcription

1 Mycoplasma genitalium: What is it and why should we care? Lisa E. Manhart, PhD, MPH rwpoll.com uwecho Last Updated: uwptc.org

2 Disclosures Service on a scientific advisory board and receipt of speaker fees and donations of equipment, test kits, and reagents from Hologic, Inc.

3 What is Mycoplasma genitalium? Mollicute - Lacks a cell wall Smallest known genome 1,2-580 kb translating to <500 genes First identified in 1981 from 2 of 13 men with NGU 3 Scanning electron micrograph Extremely fastidious - Culture only achieved by ~3-4 laboratories worldwide - Takes ~6 months 4 Computer assembled & generated 3D model 1 Glass et al, PNAS 2006; 2 Gibson et al, Science 2008; 3 Tully et al, Lancet 1981, 4 Jensen et al, J Clin Micro 1996

4 Today and Mycoplasma genitalium How common is it? Who is at increased risk for infection? What clinical syndromes occur? What should you use to treat?

5 Poll #1: How frequently do you suspect a patient has an M. genitalium infection? A. Never B. A handful of times C. Once a month D. Once a week rwpoll.com uwecho

6 How common in the General Population? Prevalence (%) ~1-3% low risk persons US (18-27) Denmark (21-23) Britain (16-44) London (15-24) Australia (15-25) London (15-27) Male Urine Female Urine Female Swab Compare to: Chlamydia: 4.0% Gonorrhea: 0.5% Manhart 2007; Andersen 2007; Sonnenberg 2016; Svenstrup 2010; Walker 2011; Oakeshott 2010

7 Much Higher Prevalence in Clinical Populations Clinical Diagnostic Test Assessment Study* Wheaton Franciscan Laboratory* Prevalence Prevalence MG GC CT TV 0 MG GC CT TV Females Males Females Males Getman et al, J Clin Micro 2016 Napierala et al, Diag Micro Inf Dis 2015; Munson et al, J Clin Micro 2016

8 Age Distribution NATSAL-3 Males Females Prevalence Prevalence Sonnenberg Int J Epi, 2015

9 Who s at Risk? (NATSAL-3) FEMALES aor (95% CI) 3.0 (1.4, 6.4) 3.7 (1.6, 8.3) 2.9 (1.3, 6.4) 2.6 (1.2, 5.4) MALES aor (95% CI) 7.3 (2.2, 24.2) 11.7 (3.1, 43.5) 5.0 (1.4, 17.5) 12.1 (3.7, 39.4) Sonnenberg et al. Int J Epi 2015

10 Poll #2: What STI syndromes have been associated with M. genitalium? A. Urethritis B. Cervicitis C. Female Infertility D. Only Urethritis & Cervicitis E. Urethritis, Cervicitis & Female Infertility (A, B, & C) rwpoll.com uwecho

11 What do the data say? Syndrome Summary risk estimate OR (95% CI) Studies accounting for CT (subset) NGU 5.5 ( ) - Female Urethritis 2.2 ( ) 2.1 ( ) Cervicitis 1.6 ( ) 1.9 ( ) PID / Endometritis 1.9 ( ) 2.0 ( ) Preterm Delivery 1.9 ( ) 2.3 ( ) Spontaneous Abortion 1.8 ( ) 2.3 ( ) Infertility 3.0 ( ) 3.7 ( ) HIV 2.0 ( ) - Lis et al, CID 2015

12 What do the data say? Syndrome Summary risk estimate OR (95% CI) Studies accounting for CT (subset) NGU 5.5 ( fold 7.0) increased risk - Female Urethritis 2.2 ( ) 2.1 ( ) Cervicitis 1.6 ( ) 1.9 ( ) 2-fold increased risk PID / Endometritis 1.9 ( ) 2.0 ( ) (Stronger when accounting for other causes of the syndromes) Preterm Delivery 1.9 ( ) 2.3 ( ) Spontaneous Abortion 1.8 ( ) 2.3 ( ) Infertility 3.0 ( ) 3.7 ( ) HIV 2.0 ( ) - Lis et al, CID 2015

13 MG Causes Damage to Fallopian Tube Tissue Normal (control) tissue after 6 days incubation Tissue 6 days after infection with C. trachomatis Tissue 6 days after infection with M. genitalium Baczynska et al, Hum Reprod 2007

14 Poll #3: If you suspect M. genitalium infection, where could you get a test performed? A. Major Medical Center Laboratory B. Research Laboratory C. Commercial Laboratory D. Nowhere tests are not available rwpoll.com uwecho

15 M. genitalium testing No FDA-approved test Sensitivity Specificity PPV NPV % % % % Aptima TMA (CE Mark) Male Urine Female Vaginal Swab Diagenode S-DiaMGTV (CE Mark) Urine Swab SpeeDx (CE-IVD Mark) Specimen type not specified Adapted from Charlotte Gaydos

16 M. genitalium No FDA-approved test, BUT... Laboratory Test Description Sample Types Cost* Mycoplasma genitalium NAA Endocervical Swab Vaginal Swab Male Urethral Swab (Aptima swab transport) First-void Urine (Aptima urine transport) $100 (swab or urine) SureSwab Mycoplasma genitalium Vaginal swab (Aptima Vaginal Swab Collection Kit) $167 Real-Time PCR *WA state pricing for direct patient billing CPT Code 87798: Infectious agent detection by nucleic acid (DNA or RNA); not otherwise specified; amplified probe technique, each organism

17 Poll #4: What is your therapy of choice for urethritis or cervicitis? A. Doxycycline 100mg bid x 7 days B. Azithromycin 1 g single dose C. Other D. Wait to receive test results and treat based on result rwpoll.com uwecho

18 M. genitalium & Syndromic Therapy Female Cervicitis & Male Urethritis % 67% Recommended Regimen 60 Doxycycline 100 mg bid x 7 days 40 45% 40% 31% 30% AZM DOX OR 20 Azithromycin 1 g orally in a single dose 0 Mena 2009 Schwebke 2011 Manhart 2013

19 CDC 2015 STD Treatment Guidelines The 1-g single dose of azithromycin was significantly more effective against M. genitalium than doxycycline in two randomized urethritis treatment trials and is preferred over doxycycline. However, resistance to azithromycin appears to be rapidly emerging. Moxifloxacin (400mg daily x 7, 10, or 14 days) has been successfully used to treat M. genitalium in men and women with previous treatment failures. Although generally considered effective, studies in Japan, Australia, and the United States have reported moxifloxacin treatment failures after the 7 day regimen. CDC 2015 STD Treatment Guidelines

20 Macrolide resistance in the U.S. 60 Prevalence of MRMM % 50.8% 42.0% 0 Overall Females Males Getman et al, J Clin Micro 2016

21 Quinolones Treatment outcomes after moxifloxacin (400mg x 7, 10, or 14 days) Bradshaw 2006 Ross 2006 Jernberg 2008 Bradshaw 2008 Terada 2012 Terada % Gesink 2012 Twin 2012 Walker 2013 Anagrius 2013 Manhart % Couldwell % Gundevia % Guschin 2015 Bissessor % % with Microbiologic Cure 14 days 10 days 7 days

22 Resistant M. genitalium infections: What do we do? Pristinamycin 1 g qid x 10 days (Not available in US) - Initial response good, but - Treatment failures appearing in Australia (C. Bradshaw, personal communication) Spectinomycin 2g IM x 7 days - Successful in a single case report (J. Jensen, personal communication)

23 Discussion