Guidance: Screening, Diagnosis, and Treatment of Mycoplasma genitalium

Guidance: Screening, Diagnosis, and Treatment of Mycoplasma genitalium

Purpose of This Guidance

Lead authors: Daniela E. DiMarco, MD, MPH,1 and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

This guidance on the screening, diagnosis, and treatment of Mycoplasma genitalium infection was developed by the New York State Department of Health (NYSDOH) AIDS Institute (AI) Clinical Guidelines Program. By addressing the care of adults with and without HIV who have acquired sexually transmitted M. genitalium, this guidance aims to accomplish the following:

  • Provide clinicians with recommendations on screening and diagnostic testing and highlight common clinical syndromes.
  • Review treatment regimens with demonstrated activity against M. genitalium.
  • Integrate current evidence-based clinical recommendations and expert advice regarding testing and treatment of M. genitalium infection.

The literature on this topic and the disease epidemiology are evolving rapidly. To prepare this guidance, the authors conducted a literature search through MEDLINE, reviewed conference abstracts from the 2019 STI & HIV World Congress and the 2019 Conference on Retroviruses and Opportunistic Infections, and reviewed guidelines published from the U.S. Centers for Disease Control and Prevention; International Union Against Sexually Transmitted Infections; British Association for Sexual Health and HIV; Australian Society for HIV, Viral Hepatitis and Sexual Health Medicine; and Public Health Agency of Canada.

An emerging cause of sexually transmitted infections (STIs): M. genitalium, a bacterium discovered in the 1980s [Tully, et al. 1981] infects epithelial cells of the urogenital tract [McGowin and Totten 2017]. The organism is now recognized as an emerging cause of STIs worldwide [Tien, et al. 2019] and has specifically been linked to urethritis [Horner, et al. 1993; Horner and Martin 2017], cervicitis [Manhart, et al. 2003], and pelvic inflammatory disease [Haggerty, et al. 2008; Totten, et al. 2008; Bjartling, et al. 2012]. Some studies have raised concerns about associations between M. genitalium infection and infertility and pregnancy complications, such as preterm delivery, but there is a paucity of high-quality evidence on these topics [Oakeshott, et al. 2004; Hitti, et al. 2010; Taylor-Robinson and Lamont 2011; Lis, et al. 2015; Wiesenfeld and Manhart 2017]. Treatment of M. genitalium infection is challenging in an era of increasing antimicrobial resistance across multiple drug classes. The availability of nucleic acid amplification tests approved by the U.S. Food and Drug Administration raises the possibility of increased detection of M. genitalium infection, leading to increased treatment with antibiotics, and potentially, more widespread multidrug resistance [Singh and Manhart 2020].

Prevalence of M. genitalium infection: In the early 2000s, prevalence estimates suggested that M. genitalium infection was more common than gonorrheal infections but less common than chlamydial infections [Manhart, et al. 2007]. Subsequent studies demonstrated that prevalence rates of M. genitalium infection vary by population and clinical setting, with general population estimates ranging between <1% and 4% worldwide, and rates among individuals with STIs reported to be as high as 38% [Casin, et al. 2002; Manhart, et al. 2007; Baumann, et al. 2018]. Although these ranges are based on data from multiple countries and populations and include a mix of symptomatic and asymptomatic individuals, most reports suggest that asymptomatic infection is common [Manhart, et al. 2007; Huppert, et al. 2008; Gesink, et al. 2016]. Coinfection with other STIs, such as Chlamydia trachomatis or Neisseria gonorrhoeae infection can occur [Hooton, et al. 1988; Mena, et al. 2002; Huppert, et al. 2008; Gaydos, et al. 2009; Harrison, et al. 2019].

1University of Rochester School of Medicine and Dentistry, Infectious Diseases Division

References

Baumann L, Cina M, Egli-Gany D, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect 2018;94(4):255-262. [PMID: 29440466]

Bjartling C, Osser S, Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012;206(6):476.e471-478. [PMID: 22483084]

Casin I, Vexiau-Robert D, De La Salmoniere P, et al. High prevalence of Mycoplasma genitalium in the lower genitourinary tract of women attending a sexually transmitted disease clinic in Paris, France. Sex Transm Dis 2002;29(6):353-359. [PMID: 12035026]

Gaydos C, Maldeis NE, Hardick A, et al. Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis in women attending sexually transmitted disease clinics. Sex Transm Dis 2009;36(10):598-606. [PMID: 19704398]

Gesink D, Racey CS, Seah C, et al. Mycoplasma genitalium in Toronto, Ont: Estimates of prevalence and macrolide resistance. Can Fam Physician 2016;62(2):e96-101. [PMID: 27331225]

Haggerty CL, Totten PA, Astete SG, et al. Failure of cefoxitin and doxycycline to eradicate endometrial Mycoplasma genitalium and the consequence for clinical cure of pelvic inflammatory disease. Sex Transm Infect 2008;84(5):338-342. [PMID: 18445635]

Harrison SA, Olson KM, Ratliff AE, et al. Mycoplasma genitalium coinfection in women with Chlamydia trachomatis infection. Sex Transm Dis 2019;46(10):e101-e104. [PMID: 31517808]

Hitti J, Garcia P, Totten P, et al. Correlates of cervical Mycoplasma genitalium and risk of preterm birth among Peruvian women. Sex Transm Dis 2010;37(2):81-85. [PMID: 20051932]

Hooton TM, Roberts MC, Roberts PL, et al. Prevalence of Mycoplasma genitalium determined by DNA probe in men with urethritis. Lancet 1988;1(8580):266-268. [PMID: 2893083]

Horner PJ, Gilroy CB, Thomas BJ, et al. Association of Mycoplasma genitalium with acute non-gonococcal urethritis. Lancet 1993;342(8871):582-585. [PMID: 8102721]

Horner PJ, Martin DH. Mycoplasma genitalium infection in men. J Infect Dis 2017;216(suppl_2):S396-S405. [PMID: 28838074]

Huppert JS, Mortensen JE, Reed JL, et al. Mycoplasma genitalium detected by transcription-mediated amplification is associated with Chlamydia trachomatis in adolescent women. Sex Transm Dis 2008;35(3):250-254. [PMID: 18490867]

Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015;61(3):418-426. [PMID: 25900174]

Manhart LE, Critchlow CW, Holmes KK, et al. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis 2003;187(4):650-657. [PMID: 12599082]

Manhart LE, Holmes KK, Hughes JP, et al. Mycoplasma genitalium among young adults in the United States: an emerging sexually transmitted infection. Am J Public Health 2007;97(6):1118-1125. [PMID: 17463380]

McGowin CL, Totten PA. The unique microbiology and molecular pathogenesis of Mycoplasma genitalium. J Infect Dis 2017;216(suppl_2):S382-s388. [PMID: 28838077]

Mena L, Wang X, Mroczkowski TF, et al. Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans. Clin Infect Dis 2002;35(10):1167-1173. [PMID: 12410476]

Oakeshott P, Hay P, Taylor-Robinson D, et al. Prevalence of Mycoplasma genitalium in early pregnancy and relationship between its presence and pregnancy outcome. Bjog 2004;111(12):1464-1467. [PMID: 15663138]

Singh AE, Manhart L. Is it time for the United States and Canada to reconsider macrolides as the first-line empiric treatment for males with symptomatic urethritis? Clin Infect Dis 2020;70(5):811-813. [PMID: 30972414]

Taylor-Robinson D, Lamont RF. Mycoplasmas in pregnancy. Bjog 2011;118(2):164-174. [PMID: 21091927]

Tien V, Punjabi C, Holubar MK. Antimicrobial resistance in sexually transmitted infections. J Travel Med 2019. [PMID: 31840758]

Totten PA, Taylor-Robinson D, Jensen JS. Chapter 41: Genital Mycoplasmas, Sexually Transmitted Diseases. In: Holmes KK, Sparling PF, Stamm WE et al., editors. 4th ed. New York, NY: McGraw-Hill; 2008. 709-736.

Tully JG, Taylor-Robinson D, Cole RM, et al. A newly discovered mycoplasma in the human urogenital tract. Lancet 1981;1(8233):1288-1291. [PMID: 6112607]

Wiesenfeld HC, Manhart LE. Mycoplasma genitalium in women: current knowledge and research priorities for this recently emerged pathogen. J Infect Dis 2017;216(suppl_2):S389-s395. [PMID: 28838078]

Risk Factors and Clinical Syndromes

Lead authors: Daniela E. DiMarco, MD, MPH, and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

Risk factors for infection: Risk factors for infection with Mycoplasma genitalium include tobacco use [Manhart, et al. 2003; Balkus, et al. 2018], multiple sex partners [Manhart, et al. 2003; Manhart, et al. 2007; Crowell, et al. 2019], vaginal sex [Manhart, et al. 2007], black race [Manhart, et al. 2007], younger age (≤22 years) in cisgender women [Manhart, et al. 2003; Mobley, et al. 2012], and HIV infection [Lusk, et al. 2011; Crowell, et al. 2019].

Transmission is presumed to occur through mucosal contact during penile-vaginal and penile-anal sex, as demonstrated by concordance between partners [Totten, et al. 2008; Cina, et al. 2019]. There is no current evidence of oral-genital transmission.

Associated clinical syndromes: Although asymptomatic infection is commonly reported, M. genitalium infection has been associated with the clinical syndromes of urethritis, cervicitis, and pelvic inflammatory disease (PID). In cisgender women, M. genitalium has been detected in urine [Gaydos CA, et al. 2019], vaginal, and cervical specimens, as well as endometrial tissue samples [Cohen, et al. 2005; Haggerty, et al. 2006]. In cisgender men, M. genitalium has been detected in anorectal and urethral samples [Maeda, et al. 1998; Crowell, et al. 2019]. At present, there is insufficient evidence that M. genitalium is a primary cause of proctitis and no evidence that it is a cause of pharyngitis or epididymo-orchitis.

Evidence is strong that M. genitalium is a causative agent of urethritis and persistent or recurrent urethritis in cisgender men [Totten, et al. 2001; Wikstrom and Jensen 2006; Horner and Martin 2017]. Symptoms of urethritis in this group have been described as milder than those of gonococcal urethritis and similar to those of Chlamydia trachomatis urethral infection [Mena, et al. 2002]. In a study among heterosexual men at an STD clinic in Seattle, Washington, M. genitalium was found in 22% of participants with nongonococcal urethritis and 4% of controls. In a multivariate analysis controlling for multiple factors, including prior urethritis, M. genitalium was associated with a more than 6-fold increase in the risk of urethritis [Totten, et al. 2001].

Several studies conducted in STI clinics in the United States and internationally have found statistically significant associations between detection of M. genitalium and cervicitis, independent of C. trachomatis infection, with a Seattle study noting a 3-fold increase in risk for mucopurulent cervicitis [Manhart, et al. 2003; Gaydos C, et al. 2009; Lusk, et al. 2011; Bjartling, et al. 2012]. In a cohort of women with HIV in New Orleans, Louisiana, cure of M. genitalium infection was associated with resolution of histologic markers of cervical inflammation, suggesting this pathogen was the cause of cervicitis in these women [Dehon, et al. 2016].

A 2015 meta-analysis found a statistically significant association between M. genitalium infection and an increased risk of both cervicitis and PID, even when accounting for coinfections with other STIs [Lis, et al. 2015]. M. genitalium–associated PID symptoms may be more indolent and chronic than gonococcal disease [Short, et al. 2009].

References

Balkus JE, Manhart LE, Jensen JS, et al. Mycoplasma genitalium infection in Kenyan and US women. Sex Transm Dis 2018;45(8):514-521. [PMID: 29465649]

Bjartling C, Osser S, Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012;206(6):476.e471-478. [PMID: 22483084]

Cina M, Baumann L, Egli-Gany D, et al. Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis. Sex Transm Infect 2019;95(5):328-335. [PMID: 31055469]

Cohen CR, Mugo NR, Astete SG, et al. Detection of Mycoplasma genitalium in women with laparoscopically diagnosed acute salpingitis. Sex Transm Infect 2005;81(6):463-466. [PMID: 16326847]

Crowell TA, Lawlor J, Lombardi K, et al. Anorectal and urogenital Mycoplasma genitalium in Nigerian men who have sex with men and transgender women: Prevalence, incidence, and association with HIV. Sex Transm Dis 2019. [PMID: 31880740]

Dehon PM, Hagensee ME, Sutton KJ, et al. Histological evidence of chronic Mycoplasma genitalium-induced cervicitis in HIV-infected women: A retrospective cohort study. J Infect Dis 2016;213(11):1828-1835. [PMID: 26783349]

Gaydos C, Maldeis NE, Hardick A, et al. Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis in women attending sexually transmitted disease clinics. Sex Transm Dis 2009;36(10):598-606. [PMID: 19704398]

Gaydos CA, Manhart LE, Taylor SN, et al. Molecular testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study. J Clin Microbiol 2019;57(11). [PMID: 31484702]

Haggerty CL, Totten PA, Astete SG, et al. Mycoplasma genitalium among women with nongonococcal, nonchlamydial pelvic inflammatory disease. Infect Dis Obstet Gynecol 2006;2006:30184. [PMID: 17485798]

Horner PJ, Martin DH. Mycoplasma genitalium infection in men. J Infect Dis 2017;216(suppl_2):S396-S405. [PMID: 28838074]

Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015;61(3):418-426. [PMID: 25900174]

Lusk MJ, Konecny P, Naing ZW, et al. Mycoplasma genitalium is associated with cervicitis and HIV infection in an urban Australian STI clinic population. Sex Transm Infect 2011;87(2):107-109. [PMID: 21071566]

Maeda S, Tamaki M, Nakano M, et al. Detection of Mycoplasma genitalium in patients with urethritis. J Urol 1998;159(2):405-407. [PMID: 9649249]

Manhart LE, Critchlow CW, Holmes KK, et al. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis 2003;187(4):650-657. [PMID: 12599082]

Manhart LE, Holmes KK, Hughes JP, et al. Mycoplasma genitalium among young adults in the United States: an emerging sexually transmitted infection. Am J Public Health 2007;97(6):1118-1125. [PMID: 17463380]

Mena L, Wang X, Mroczkowski TF, et al. Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans. Clin Infect Dis 2002;35(10):1167-1173. [PMID: 12410476]

Mobley VL, Hobbs MM, Lau K, et al. Mycoplasma genitalium infection in women attending a sexually transmitted infection clinic: diagnostic specimen type, coinfections, and predictors. Sex Transm Dis 2012;39(9):706-709. [PMID: 22902666]

Short VL, Totten PA, Ness RB, et al. Clinical presentation of Mycoplasma genitalium infection versus Neisseria gonorrhoeae infection among women with pelvic inflammatory disease. Clin Infect Dis 2009;48(1):41-47. [PMID: 19025498]

Totten PA, Schwartz MA, Sjostrom KE, et al. Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men. J Infect Dis 2001;183(2):269-276. [PMID: 11120932]

Totten PA, Taylor-Robinson D, Jensen JS. Chapter 41: Genital Mycoplasmas, Sexually Transmitted Diseases. In: Holmes KK, Sparling PF, Stamm WE et al., editors. 4th ed. New York, NY: McGraw-Hill; 2008. 709-736.

Wikstrom A, Jensen JS. Mycoplasma genitalium: a common cause of persistent urethritis among men treated with doxycycline. Sex Transm Infect 2006;82(4):276-279. [PMID: 16877573]

Laboratory Testing

Lead authors: Daniela E. DiMarco, MD, MPH, and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

RECOMMENDATIONS
Laboratory Testing
  • Clinicians should not routinely screen for Mycoplasma genitalium in asymptomatic individuals. (A3)
  • When testing is indicated, clinicians should use nucleic acid amplification testing (NAAT) to diagnose M. genitalium, with resistance testing if available. (A3)

Laboratory tests: M. genitalium bacteria have no cell wall and can take months to grow in culture; thus, traditional methods of diagnosis with gram stain or culture are not useful. Diagnosis was difficult until molecular tests, such as NAAT, became available. NAAT is the preferred, U.S. Food and Drug Administration (FDA)-approved diagnostic method for M. genitalium infection. The FDA-approved tests currently available for detection of M. genitalium are the Aptima™ Mycoplasma genitalium Assay (Hologic, Inc) and the cobas® TV/MG Assay (Roche Diagnostics). 

Molecular tests that detect both M. genitalium and antibiotic-associated resistance mutations are available in some countries. These combination tests are not currently commercially available in the United States but are anticipated to become available in the near future. At present, resistance assays are most useful in determining macrolide resistance. The association of certain resistance mutations with clinical treatment failure is inconsistent, particularly for quinolone antibiotics [Conway, et al. 2019]. However, resistance testing has been demonstrated as a clinically useful tool to guide treatment, resulting in high cure rates, as evidenced by the resistance-guided antimicrobial therapy model [Durukan, et al. 2019] described in more detail in the section on Treatment in this guideline. As with other infections associated with emerging antibiotic resistance, resistance testing may help minimize use of broader spectrum antibiotics with greater potential for adverse effects and improve likelihood of treatment success.

Diagnostic testing: Diagnostic testing may be considered for individuals with urethritis, cervicitis, or pelvic inflammatory disease (PID). Some experts advise that diagnostic testing for M. genitalium be performed only in individuals with symptomatic urethritis, cervicitis, or PID [ASHA 2017; Soni, et al. 2019]; others advise that testing be performed only in those with negative gonorrhea and chlamydia test results or who do not respond to first-line empiric treatment [Expert Working Group 2016; Jensen, et al. 2016]. Nonresponse to first-line treatment increases the index of suspicion for M. genitalium as a causative agent. Reinfection from untreated sexual partners and infection with other STIs such as Trichomonas vaginalis or herpes simplex virus are important to include in the differential diagnosis for individuals with recurrent or persistent STI syndromes.

Specimen collection: Acceptable specimen types for M. genitalium testing include first-void urine and swabs from the vagina, endocervix, cervix, or penile urethra/urethral meatus [Hologic Inc. 2017; Gaydos, et al. 2019]. Self-collected specimens are acceptable for vaginal, urine, and urethral meatus sites, although swabs from the urethral meatus have <90% sensitivity [Hologic Inc. 2017; Gaydos, et al. 2019]. There is insufficient evidence to recommend extragenital testing for M. genitalium in any population. For cisgender women, vaginal swabs are preferred over urine specimens because of greater sensitivity [Mobley, et al. 2012; Gaydos, et al. 2019]; for cisgender men, urine specimens are preferred over urethral meatus swabs but have sensitivity comparable to that of traditional urethral swabs [Gaydos, et al. 2019]. There is currently no published evidence to support a preferred testing site or type of specimen in individuals who have a neovagina or neopenis.

Screening: Currently available evidence does not support routine screening for M. genitalium in asymptomatic individuals or in any specific population [Golden, et al. 2017; Horner and Martin 2017]. Prevalence estimates of M. genitalium in the general population are low, antimicrobial resistance is increasing, and treatment options are limited [Golden, et al. 2017; Horner and Martin 2017; Baumann, et al. 2018; Fernandez-Huerta, et al. 2019].

References

ASHA. Australian STI management guidelines for use in primary care. 2018 Jul 11. http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium [accessed 2019 Dec 31]

Baumann L, Cina M, Egli-Gany D, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect 2018;94(4):255-262. [PMID: 29440466]

Conway RJH, Cook S, Malone C, et al. Clearance of Mycoplasma genitalium infection with moxifloxacin in the presence of quinolone resistance-associated mutations. Sex Transm Dis 2019. [PMID: 31738298]

Durukan D, Read TRH, Murray G, et al. Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability. Clin Infect Dis 2019. [PMID: 31629365]

Expert Working Group. Canadian guidelines on sexually transmitted infections. 2017 Jun 1. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/2016-updates-summary.html#a2.6 [accessed 2019 Dec 31]

Fernandez-Huerta M, Barbera MJ, Esperalba J, et al. Prevalence of Mycoplasma genitalium and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening: a cross-sectional study. Sex Transm Infect 2019. [PMID: 31451540]

Gaydos CA, Manhart LE, Taylor SN, et al. Molecular testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study. J Clin Microbiol 2019;57(11). [PMID: 31484702]

Golden MR, Workowski KA, Bolan G. Developing a public health response to Mycoplasma genitalium. J Infect Dis 2017;216(suppl_2):S420-s426. [PMID: 28838079]

Hologic Inc. Aptima Mycoplasma genitalium Assay Package Insert. 2017 May. https://www.hologic.com/sites/default/files/package-insert/AW-14170-001_005_01.pdf [accessed 2020 Feb 24]

Horner PJ, Martin DH. Mycoplasma genitalium infection in men. J Infect Dis 2017;216(suppl_2):S396-S405. [PMID: 28838074]

Jensen JS, Cusini M, Gomberg M, et al. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2016;30(10):1650-1656. [PMID: 27505296]

Mobley VL, Hobbs MM, Lau K, et al. Mycoplasma genitalium infection in women attending a sexually transmitted infection clinic: diagnostic specimen type, coinfections, and predictors. Sex Transm Dis 2012;39(9):706-709. [PMID: 22902666]

Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS 2019;30(10):938-950. [PMID: 31280688]

Treatment

Lead authors: Daniela E. DiMarco, MD, MPH, and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

RECOMMENDATIONS
Treatment
  • Clinicians should prescribe treatment with oral moxifloxacin 400 mg daily for 7 to 14 days for individuals with confirmed cases of symptomatic Mycoplasma genitalium infection. (B2)
  • Clinicians should consider using doxycycline for empiric treatment of persistent or recurrent urethritis or cervicitis while awaiting M. genitalium test results, to facilitate lead-in to a 2-step treatment approach. (B2)

General considerations: Azithromycin, doxycycline, and moxifloxacin are the most frequently used antibacterial agents for M. genitalium treatment (Table). Single-dose azithromycin has been a standard treatment for M. genitalium infection [Mena, et al. 2009; Schwebke, et al. 2011]; however, there is recent evidence of emerging macrolide resistance and treatment failure associated with the single 1 g oral dose [Manhart, et al. 2013; Gesink, et al. 2016; Horner, et al. 2018]. Early reports of superior cure rates with an extended course of azithromycin have not been confirmed in more recent studies [Anagrius, et al. 2013; Horner, et al. 2018]. Prevalence of macrolide-associated resistance mutations is now >50% in many areas and was recently found to be >62% in a sexually transmitted infection (STI) clinic population in the United States [Bachmann, et al. 2019]. A 2015 review of the literature noted that treatment efficacy for both azithromycin and doxycycline has been declining [Manhart, et al. 2015].

Like azithromycin, moxifloxacin had documented cure rates approaching 100%, but in the last decade, that number has fallen below 90% with monotherapy in some studies [Manhart, et al. 2015; Li, et al. 2017]. In the 2015 review noted above, levofloxacin and ofloxacin had lower cure rates than fourth-generation quinolones (including moxifloxacin, gatifloxacin, and sitafloxacin) [Manhart, et al. 2015]. A meta-analysis of primarily observational studies compared efficacy of 7- and 10-day treatment durations for moxifloxacin and found no significant difference [Li, et al. 2017]. For pelvic inflammatory disease (PID) related to M. genitalium or in the PID clinical syndrome in general, a 14-day course of moxifloxacin treatment was found to be effective [Ross, et al. 2006; Judlin, et al. 2010; Latimer, et al. 2019a; Ovens, et al. 2019]. Because of emerging resistance overall and a lack of treatment alternatives, moxifloxacin has not been recommended for first-line empiric use in existing international guidelines [Expert Working Group 2016; Jensen, et al. 2016; ASHA 2017; Soni, et al. 2019].

The Table, below, summarizes current treatment options.

Table: Antimicrobial Treatment Regimens for Mycoplasma genitalium Infection
Oral Regimens Considerations
Moxifloxacin 400 mg daily for 7 to 14 days [a]
  • Recommended by this committee for symptomatic, laboratory-confirmed genitalium infection.
  • Consider for use after failed empiric therapy for STI syndromes when diagnostic testing for genitalium is not available and when infection with Chlamydia trachomatis, Trichomonas vaginalis, or other STIs has been excluded or is unlikely.
  • Moxifloxacin is generally not recommended for pregnant individuals. See Special Populations > Pregnant Patients.

Azithromycin 1 g as a single dose
OR
500 mg on day 1, followed by 250 mg daily on days 2, 3, 4, and 5

  • High rates of resistance.
  • Single-dose azithromycin was considered superior to doxycycline [Mena, et al. 2009; Schwebke, et al. 2011]; however, the prevalence of resistance is now >50% in most areas [Bachmann, et al. 2019].
  • Only regimen available in the United States that does not contain drugs contraindicated in pregnancy.
Doxycycline 100 mg twice daily for 7 days, followed by azithromycin 1g on day 1, then 500 mg daily on days 2, 3, and 4
  • Two-step regimen when macrolide resistance is NOT suspected or confirmed [b].
  • Not for persistent or recurrent syndromes.
  • Doxycycline is generally not recommended for pregnant individuals. See Special Populations > Pregnant Patients.
Doxycycline 100 mg twice daily for 7 days, followed by moxifloxacin 400 mg daily for 7 to 14 days [a]
  • Two-step regimen when there is concern for macrolide resistance [b].
  • Resistance is more likely among MSM and individuals with previous exposure to azithromycin [Bercot, et al. 2019; Furegato, et al. 2019; Li, et al. 2020].
  • Doxycycline is generally not recommended for pregnant individuals. See Special Populations > Pregnant Patients.
Pristinamycin 1 g 4 times daily for 10 days
  • An option for macrolide and moxifloxacin treatment failure.
  • Not currently available in the United States or Canada.

Abbreviations: MSM, men who have sex with men; PID, pelvic inflammatory disease; STI, sexually transmitted infection.
Notes:
a. A 14-day regimen containing moxifloxacin is preferred for treatment of PID [Ross, et al. 2006; Judlin, et al. 2010; Latimer, et al. 2019a; Ovens, et al. 2019]. The evaluation and treatment for refractory PID are not limited to the management discussed here.
b. Pretreatment with doxycycline may reduce bacterial load, which may increase effectiveness of azithromycin or moxifloxacin [Durukan, et al. 2019].

A 2-step treatment approach: A 2-step approach to antimicrobial treatment has improved treatment success in published reports, leading to recommendations for 2-step treatment in Australian and UK treatment guidelines [ASHA 2017; Soni, et al. 2019]. The premise of the 2-step approach is that pretreatment with doxycycline has been shown to decrease the overall bacterial burden, making treatment with a second follow-up drug more efficacious [Bjornelius, et al. 2008; Anagrius, et al. 2013; Durukan, et al. 2019].

In Australia, cure rates have risen to >90% with the implementation of resistance-guided antimicrobial therapy (RGT) [Durukan, et al. 2019]. Individuals with an STI syndrome received 7 days of oral doxycycline 100 mg twice daily empirically and then, if found to have M. genitalium without macrolide resistance, received 2.5 g oral azithromycin over 4 days (1 g on day 1 and 500 mg daily on days 2 through 4). After initial treatment with doxycycline, individuals with macrolide-resistant M. genitalium received oral moxifloxacin 400 mg daily for 7 days. A test of cure was performed 2 to 4 weeks after treatment. The cure rate with the RGT approach was 92%, even in regions with reported quinolone resistance of 15% to 20% [Durukan, et al. 2019].

Macrolide resistance: Knowledge of the local prevalence of macrolide and quinolone resistance may help guide regimen choice, particularly when resistance testing is not readily available. Risk factors for macrolide-associated resistance mutations include a recent STI, STI coinfection, and use of antibiotics within 30 days [Furegato, et al. 2019; Li, et al. 2020]. A substudy of the ANRS IPERGAY trial found a high prevalence of antibiotic-resistant M. genitalium in men who have sex with men (MSM) taking pre-exposure prophylaxis to prevent HIV infection [Bercot, et al. 2019]. Use of azithromycin as a standard treatment for gonorrhea and chlamydia has been associated with higher rates of macrolide resistance in MSM [Anagrius, et al. 2013; Latimer, et al. 2019b]. 

In cases of treatment failure with macrolides and moxifloxacin, pristinamycin 1 g 4 times daily for 10 days has been effective in European and Australian studies [Bissessor, et al. 2015; Read, et al. 2018], but this treatment is not currently available in the United States.

STI coinfections: When coinfection with another sexually transmitted organism is present, it remains unclear based on available evidence whether M. genitalium is a true pathogen.

Test of cure: Test of cure can be considered after completion of treatment in patients who remain symptomatic. The timeframe used for test of cure in the published literature is highly variable. Existing guidelines from Europe, Australia, and the United Kingdom have recommendations ranging from ≥2 to ≥5 weeks after treatment [Jensen, et al. 2016; ASHA 2017; Soni, et al. 2019]. Testing too soon carries the risk of detecting residual noninfectious particles after treatment.

Evaluation and treatment of sex partners: Sex partners of individuals with symptomatic M. genitalium infection should be evaluated. There is insufficient evidence to clarify whether partners should receive treatment without testing or be treated only if infection is detected through a laboratory test. [Expert Working Group 2016; Jensen, et al. 2016; ASHA 2017; Soni, et al. 2019]. Now that diagnostic tests for M. genitalium are approved by the U.S. Food and Drug Administration, this Committee considers it reasonable to limit treatment to ongoing sex partners with positive test results.

References

Anagrius C, Lore B, Jensen JS. Treatment of Mycoplasma genitalium. Observations from a Swedish STD clinic. PLoS One 2013;8(4):e61481. [PMID: 23593483]

ASHA. Australian STI management guidelines for use in primary care. 2018 Jul 11. http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium [accessed 2019 Dec 31]

Bachmann L, Kirkcaldy R, Geisler W, et al. Prevalence of Mycoplasma genitalium infection, antimicrobial resistance, and symptom resolution following treatment. STI & HIV World Congress; 2019 Jul 14-17; Vancouver, Canada. https://sti.bmj.com/content/95/Suppl_1/A274.2

Bercot B, Charreau I, Rousseau C, et al. High prevalence and antibiotic resistance of M genitalium infections in MSM on PrEP. Conference on Retroviruses and Opportunistic Infections; 2019 Mar 4-7; Seattle, WA. https://www.croiconference.org/abstract/high-prevalence-and-antibiotic-resistance-m-genitalium-infections-msm-prep/

Bissessor M, Tabrizi SN, Twin J, et al. Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens. Clin Infect Dis 2015;60(8):1228-1236. [PMID: 25537875]

Bjornelius E, Anagrius C, Bojs G, et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex Transm Infect 2008;84(1):72-76. [PMID: 17932127]

Durukan D, Read TRH, Murray G, et al. Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability. Clin Infect Dis 2019. [PMID: 31629365]

Expert Working Group. Canadian guidelines on sexually transmitted infections. 2017 Jun 1. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/2016-updates-summary.html#a2.6 [accessed 2019 Dec 31]

Furegato M, Broad C, Phillips L, et al. Macrolide resistance in Mycoplasma genitalium is strongly associated with STI co-infection. STI & HIV World Congress; 2019 Jul 14-17; Vancouver, Canada. https://sti.bmj.com/content/95/Suppl_1/A271.2.info

Gesink D, Racey CS, Seah C, et al. Mycoplasma genitalium in Toronto, Ont: Estimates of prevalence and macrolide resistance. Can Fam Physician 2016;62(2):e96-101. [PMID: 27331225]

Horner P, Ingle SM, Garrett F, et al. Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis. Sex Transm Infect 2018;94(1):14-20. [PMID: 28717050]

Jensen JS, Cusini M, Gomberg M, et al. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2016;30(10):1650-1656. [PMID: 27505296]

Judlin P, Liao Q, Liu Z, et al. Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study. Bjog 2010;117(12):1475-1484. [PMID: 20716255]

Latimer RL, Read TRH, Vodstrcil LA, et al. Clinical features and therapeutic response in women meeting criteria for presumptive treatment for pelvic inflammatory disease associated with Mycoplasma genitalium. Sex Transm Dis 2019a;46(2):73-79. [PMID: 30640861]

Latimer RL, Vodstrcil LA, Read TRH, et al. Extragenital Mycoplasma genitalium infections amongst men who have sex with men. STI & HIV World Congress; 2019b Jul 14-17; Vancouver, Canada. https://sti.bmj.com/content/96/1/10

Li Y, Le WJ, Li S, et al. Meta-analysis of the efficacy of moxifloxacin in treating Mycoplasma genitalium infection. Int J STD AIDS 2017;28(11):1106-1114. [PMID: 28118803]

Li Y, Su X, Le W, et al. Mycoplasma genitalium in symptomatic male urethritis: macrolide use is associated with increased resistance. Clin Infect Dis 2020;70(5):805-810. [PMID: 30972419]

Manhart LE, Gillespie CW, Lowens MS, et al. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin Infect Dis 2013;56(7):934-942. [PMID: 23223595]

Manhart LE, Jensen JS, Bradshaw CS, et al. Efficacy of antimicrobial therapy for Mycoplasma genitalium infections. Clin Infect Dis 2015;61 Suppl 8:S802-817. [PMID: 26602619]

Mena LA, Mroczkowski TF, Nsuami M, et al. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin Infect Dis 2009;48(12):1649-1654. [PMID: 19438399]

Ovens KJ, Reynolds-Wright JJ, Cross ELA, et al. High rates of treatment failure for Mycoplasma genitalium among men and women attending a sexual health clinic. BMJ Sex Reprod Health 2019. [PMID: 31722934]

Read TRH, Jensen JS, Fairley CK, et al. Use of pristinamycin for macrolide-resistant Mycoplasma genitalium infection. Emerg Infect Dis 2018;24(2):328-335. [PMID: 29350154]

Ross JD, Cronje HS, Paszkowski T, et al. Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sex Transm Infect 2006;82(6):446-451. [PMID: 16723364]

Schwebke JR, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens–a randomized clinical trial. Clin Infect Dis 2011;52(2):163-170. [PMID: 21288838]

Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS 2019;30(10):938-950. [PMID: 31280688]

Special Populations

Lead authors: Daniela E. DiMarco, MD, MPH, and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

Pregnant patients: Moxifloxacin and doxycycline are generally not recommended for pregnant individuals. An azithromycin-only course of treatment could be considered. Given high rates of azithromycin resistance, a shared decision-making approach is warranted, balancing the risks of untreated Mycoplasma genitalium infection during pregnancy with possible adverse drug events associated with antibiotics not generally used during pregnancy.

At present, there is insufficient evidence regarding pregnancy complications and treatment benefits to recommend for or against screening in asymptomatic pregnant individuals [Wiesenfeld and Manhart 2017]; however, a meta-analysis of available studies has suggested significant associations with preterm birth and spontaneous abortion [Lis, et al. 2015]. In this same analysis, the risk of infertility was described as elevated but was not statistically significant [Lis, et al. 2015].

Individuals with HIV: Data are limited on M. genitalium infection in individuals with HIV. Although M. genitalium infection has been associated with viral shedding of HIV from the cervix in smaller studies of women with HIV in Kenya and Zimbabwe [Manhart, et al. 2008; Napierala Mavedzenge, et al. 2015], evidence for enhanced transmission with coinfection is lacking.

Transgender individuals: Data are lacking on M. genitalium infection in transgender individuals. As noted above, the specimen and site of optimal sensitivity for testing in transgender individuals have not been evaluated. There is insufficient evidence to support a recommendation for testing or treatment in asymptomatic transgender individuals.

References

Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015;61(3):418-426. [PMID: 25900174]

Manhart LE, Mostad SB, Baeten JM, et al. High Mycoplasma genitalium organism burden is associated with shedding of HIV-1 DNA from the cervix. J Infect Dis 2008;197(5):733-736. [PMID: 18266605]

Napierala Mavedzenge S, Muller EE, Lewis DA, et al. Mycoplasma genitalium is associated with increased genital HIV type 1 RNA in Zimbabwean women. J Infect Dis 2015;211(9):1388-1398. [PMID: 25404521]

Wiesenfeld HC, Manhart LE. Mycoplasma genitalium in women: current knowledge and research priorities for this recently emerged pathogen. J Infect Dis 2017;216(suppl_2):S389-s395. [PMID: 28838078]

All Recommendations

Lead authors: Daniela E. DiMarco, MD, MPH, and Marguerite A. Urban, MD, with the Medical Care Criteria Committee; September 2020

ALL RECOMMENDATIONS
Laboratory Testing
  • Clinicians should not routinely screen for Mycoplasma genitalium in asymptomatic individuals. (A3)
  • When testing is indicated, clinicians should use nucleic acid amplification testing (NAAT) to diagnose M. genitalium, with resistance testing if available. (A3)
Treatment
  • Clinicians should prescribe treatment with oral moxifloxacin 400 mg daily for 7 to 14 days for individuals with confirmed cases of symptomatic Mycoplasma genitalium infection. (B2)
  • Clinicians should consider using doxycycline for empiric treatment of persistent or recurrent urethritis or cervicitis while awaiting M. genitalium test results, to facilitate lead-in to a 2-step treatment approach. (B2)