Gale R. Burstein, MD, MPH, FAAP, FSAHM Commissioner, Erie County Department of Health, Clinical Professor of Pediatrics, SUNY at Buffalo School of Medicine.

Gale R. Burstein, MD, MPH, FAAP, FSAHM Commissioner, Erie County Department of Health, Clinical Professor of Pediatrics, SUNY at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY Faculty, NYC STD/HIV Prevention Training Center Have You Heard About the New Bug Around Town? Mycoplasma genitalium Clinical Epidemiology and Treatment Considerations

Special Acknowledgments Lisa E. Manhart, PhD Associate Professor, Epidemiology University of Washington

Boston University School of Medicine asks all individuals involved in the development and presentation of Continuing Medical Education (CME) activities to disclose all relationships with commercial interests. This information is disclosed to CME activity participants. Boston University School of Medicine has procedures to resolve apparent conflicts of interest. In addition, presenters are asked to disclose when any discussion of unapproved use of pharmaceuticals and devices is being discussed. I, Gale Burstein, MD, MPH, FAAP, FSAHM, have no commercial relationships to disclose.

Mycoplasma genitalium First isolated in 1981 1 Genital and reproductive tract disease Frequency more common than N. gonorrhoeae but less common than C. trachomatis coinfection with C. trachomatis not uncommon 1-3 1 Mena L, 2002; 2 Falk L, 2010; 3 Anagrius C, 2005

Young adults 18-24 yrs 1,2 M. genitalium: More common than you think 1 Miller 2004; 2 Manhart 2007 MGCTGCTV 3 Totten 2001; 4 Mena 2002 ; 5 Manhart 2003; 6 Huppert 2008; 7-8 Gaydos 2009a & 2009b; 9 Mobley 2012 STD Clinic/ED Attendees 3-9

Male urethritis & M. genitalium Acute urethritis 1 15% MG+ in urethritis overall 22% MG+ in CT-/GC- urethritis Summary OR = 5.5 (4.3-7.0) Persistent urethritis 2 13 41% males w/ persistent/recurrent urethritis MG+ 1 Taylor-Robinson & Jensen, Clin Microbiol Rev, 2011; 2 Sena et al, JID 2012

Female Reproductive Tract Disease & M. genitalium M. genitaliums pathogenic role less definitive in females than males Can be found in vagina, cervix, and endometrium M. genitalium in females commonly asymptomatic Detected in10-30% of clinical cervicitis cases 1-7 Detected in 2-22% of PID cases (median 10%) 8-17 evidence suggests that M. genitalium can cause PID, but less frequently than C. trachomatis 17,18 1 Falk L, 2010; 2 Anagrius C, 2005; 3 Falk L, 2005; 4 Manhart LE, 2003; 5 Gaydos C, 2009; 6 Mobley VL, 2012; 7 Lusk MJ, 2011; 8 Bjartling C, 2010; 9 Cohen CR 2002; 10 Cohen CR, 2005; 11 Haggerty CL, 2006, 12 Irwin KL, 2000; 13 Short VL, 2009; 14 Simms I, 2003; 15 Taylor- Robinson D, 2012; 16 Wiesenfeld HC, 2013; 17 Bjartling C, 2013; 18 Oakeshott P, 2010

M. genitalium Detection No FDA-approved diagnostic test BUT.. Multiplex PCR assays available in Europe Bio-Rad Dx/CT/NG/MG Assay Sacace Biotechnologies Commercial Laboratories & PCR tests CLIA certified Hologic Gen-Probe TMA assay (APTIMA Platform) Currently available only as research-use only (RUO) assay Commercially available Spring 2015? - analyte-specific reagent (ASR) platform

M. genitalium treatment M. genitalium lacks a cell wall antibiotics that target cell-wall biosynthesis are ineffective beta-lactams including penicillins and cephalosporins Given diagnostic challenges, treatment of most M. genitalium infections will occur in context of syndromic management for STD syndromes

M. Genitalium treatment Recommended NGU & Cervicitis Rx 1 Azithromycin 1g (single dose) Doxycycline 100mg bid x 7d Microbiologic Cure (median; observational studies) Doxycycline: 37% (range 17-94%) Azithromycin: 91% (range 69-100%) 1 CDC STD Treatment Guidelines, 2010

Treatment of M. genitalium Randomized Controlled Trials Doxycycline (100mg bid x 7d) vs. Azithromycin (1g) Microbiologic Cure (%)

Azithromycin resistance Macrolide resistance mediating mutation (MRMM) SNPs in region V of 23S rRNA gene inhibit macrolide binding % tested specimens w/ macrolide resistance

PID Treatment (outpatient) 1 57% of MG+ w/ endometritis on biopsy had persistent endometritis 30 days after Rx with Cefoxitin PLUS Doxycycline 2 1 CDC STD Treatment Guidelines, 2010; 2 Haggerty 2008 Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice daily for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days

Treatment Effectiveness Moxifloxacin 400mg x 7-14d 7 days 10 days 14 days

Challenges M. genitalium causes disease Acknowledged cause of male urethritis 2x increased risk for cervicitis, PID, and pre-term delivery Infertility risk also probably BUT Poor efficacy of standard therapies Resistance appears to be rapidly emerging Limited data on antimicrobial resistance patterns in U.S. No FDA-approved assay

Recommendations Syndromic therapy for NGU, cervicitis, PID still effective in most cases Consider M. genitalium in cases of treatment failure Moxifloxacin generally effective Consider testing high-risk populations for M. genitalium as diagnostic tests become more readily available

Persistent NGU Treatment Recommended regimens: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose PLUS Azithromycin 1 g orally in a single dose (if not used for initial episode) If treatment failure: Moxifloxacin 400 mg PO x 7d effective for NGU treatment failures due to M. genitalium

Questions Discussion KOL Meeting September 15-18, 2013

Gale R. Burstein, MD, MPH, FAAP, FSAHM Commissioner, Erie County Department of Health, Clinical Professor of Pediatrics, SUNY at Buffalo School of Medicine.

Documents

genitalium treatment

genitalium acute urethritis

genitalium detection

bjartling c

male urethritis

gaydos c

anagrius c

urethritis summary