Mycoplasma genitalium

M. genitalium is an emerging STI and important cause of non-gonococcal, non-chlamydial urethritis and cervicitis. It was first identified in 1980. Many aspects of research including pathogenicity and treatment recommendations have been hampered by difficulties in detecting and culturing this bacteria. Relatively recent advances in molecular microbiology have led to progress in determining clinical significance, community-based  investigation and  management of this infection. However, there are still unanswered questions (especially regarding potential complications) and molecular resistance testing will likely be required to assist with significant issues related to increasing antibiotic resistance.

Organism

M. genitalium is a mollicute class bacteria. It is of several types of mycoplasma in the human genital tract, not all are pathogens.

Characteristics include:

  • one of the smallest bacteria
  • extremely slow growing
  • lacks a peptidoglycan cell wall (beta-lactams and other antibiotics targeting the cell wall will be ineffective)
Clinical presentation

Urethritis

Symptoms: dysuria, urethral discharge, meatal irritation.

There is strong evidence for M. genitalium as a cause of acute and chronic urethritis in men. It is thought that up to a third of non-chlamydial, non-gonococcal urethritis may be due to M. genitalium.

Cervicitis, Endometritis and PID

Symptoms: dysuria, vaginal discharge, pain with sex, pelvic pain, inter-menstrual bleeding, post-coital bleeding.

A significant association also exists for cervicitis and endometritis and increasing studies and meta-analysis support a role in pelvic inflammatory disease (PID). As with chlamydia, it is thought that there will likely be a higher proportion of asymptomatic presence in women, but testing of asymptomatic women or men is not recommended. 

Testing for M. genitalium is recommended as a second line test:

  • in cases where a man or woman re-presents with symptoms consistent with urethritis or cervicitis after appropriate empiric therapy and baseline testing for chlamydia and gonorrhoea

Testing for M. genitalium is recommended as a first-line test:

  • in women who are suspected of having an upper tract infection, PID or endometritis.

Proctitis

In MSM with  symptomatic proctitis, M. genitalium is more common in HIV positive than negative men.

Testing for Mycoplasma genitalium should be:

  • considered as a first line test in HIV positive MSM with symptomatic proctitis 
  • recommended as a second-line test in MSM with symptomatic proctitis if baseline tests negative for chlamydia, gonorrhoea and herpes. 

Epididymitis, sexually acquired reactive arthritis (SARA), acute conjunctivitis and tubal factor infertility

Given the association with the above conditions and other STIs, most notably chlamydia, it is plausible that there could be a causal association withM. genitalium. Cases of epididymitis, SARA, and conjunctivitis associated with M. genitalium have been described in the literature. In addition, seroprevalence studies are suggestive of a possible link with Mycoplasma genitalium and infertility. However, the data to date is considered inconclusive and more study is required for all of the above conditions. 

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Investigations

Testing for M. genitalium is performed by NAAT technology.  Standard microscopy and culture will not detect this infection.

Testing recommendations

Asymptomatic individuals

  • Do not test, unless contact of known infection, then test as per symptomatic individuals

Symptomatic individuals

  • M. genitalium testing is indicated in cases where a man or woman re-presents with symptoms consistent with urethritis or cervicitis after appropriate empiric therapy and baseline testing for chlamydia and gonorrhea.

Males with urethritis 

  • FVU NAAT usually second-line test
Women with cervicitis or PID 
  • FVU + [SOLVS or endocervical swab (no transport medium)]
  • NAAT tests: Usually second-line test in uncomplicated cervicitis. First line test if upper tract infection is suspected. 

Proctitis 

  • Rectal NAAT (no transport medium)
  • Consider as a first-line test, in HIV positive MSM with symptomatic proctitis and as a second-line test in MSM with symptomatic proctitis if baseline tests negative for chlamydia, gonorrhoea, and herpes.

Note:

Most PCR testing to date has been 'in-house' developed tests (In WA this was performed mostly through Pathwest.) However more commercially available tests are expected in 2016 - 2017 and this may change established testing pathways over time.

FVU PCR for M. genitalium was found to be 95% sensitive in older studies for both men and women, it out-performed other swab sites but greater sensitivity was achieved in women by collecting cervical as well as FVU samples.

Later studies suggested vaginal samples out-performed cervical tests and FVU. Caution should be used in the interpretation of these findings and given the suspected release of new testing platforms, it may be prudent to discuss the appropriate test with your relevant laboratory based on their test's individual performance.

Ensure appropriate testing for other STIs such as chlamydia and gonorrhoea is performed, as well as screening for syphilis and BBVs.

Treatment

Macrolide resistance has been an increasing issue in Australia with over 30% of individuals failing therapy with a 1 G stat dose of Azithromycin in a recent study. Therefore a test of cure should be performed at three weeks.

First line therapy 

  • Extended course Azithromycin 500mg day 1 then 250mg for the next 4 days IF not already pre-treated with 1 G Azithromycin as empiric therapy in symptomatic individuals

Due to the development of resistance and a very limited  number of second and third-line therapy options, it is recommended to refer or discuss cases with a sexual health physician prior to consideration of further therapy.

Education counselling and prevention

Patients should be educated regarding:

  • The fact that we are still learning about this bacteria and the effects, including long-term complications it may or may not have on the body
  • The fact that this bacteria can be difficult to treat, therefore follow-up testing is important to ensure it has been cured
  • The fact that there are only a limited number of treatment options due to treatment resistance. Reinfection, by having sex with unsuccessfully treated or untreated partners may  increase the likelihood of development of treatment resistance. (see section below regarding partners)
  • No sex for 7 days after treatment, ideally no unprotected sex until after successfully proven treatment, by test of cure at 3 weeks.
Management of partners
  • Partners should be tested and treated with an appropriately sensitive antibiotic choice, if required
  • If the patient has proven treatment resistance, then the partners should likewise be treated with an appropriate next-line treatment option. There is little benefit in treating partners exposed to a macrolide  resistant infection with Azithromycin
  • It is recommended to ensure that all sexual contacts over the last 6 months are tested specifically for M. genitalium
  • Ensure patient provides written name of infection to give to their partners to then  pass on to health care provider in order to facilitate  appropriate testing. Patients and their partners may not realize that M. genitalium will not be found on routine STI screening and has to be specifically requested.
Follow up
  • Test of cure should be performed 3 weeks after therapy is complete. Test of re-infection at 3 months with other STI’s and window period serology should be encouraged. 
  • Encourage patients not to have unprotected sexual intercourse until they and all their partners have negative tests
  • Ensure testing for other STIs such as chlamydia and gonorrhoea was performed, as well as appropriate screening for syphilis and BBVs
  • Also follow-up treatment compliance, partner notification, and abstinence / condom use.
  • Resistant Mycoplasma genitalium should be referred to a sexual health physician for review.

Infection during pregnancy

There is a lack of sufficient data to draw conclusions of the effect of M. genitalium on pregnancy. Prevalence rates have been lower in studies where pregnant populations have been examined. Early studies have suggested there may be an association with preterm birth and early pregnancy loss, but more evidence is required. Similarly, more evidence is required to determine a possible link to infertility.

Treatment with a 1g dose of Azithromycin has been deemed acceptable in pregnancy for the treatment of Chlamydia and could be used for this indication.

Public health issues

There is no clear data to suggest the best period to contact trace and 6 months had been used as the default standard.

At this time, Mycoplasma genitalium is not a notifiable infection.