National Guideline for the Management of Infection with Mycoplasma Genitalium

This summary is currently being updated

Overview

Mycoplasma genitalium (M. genitalium) is the smallest known self-replicating bacterium that can be detected not only in the genitourinary tract, but also in the rectal and respiratory tracts. M. genitalium is associated with several conditions, such as recurrent and persistent urethritis, pelvic inflammatory disease, postcoital bleeding, endometritis, preterm delivery, and sexually acquired reactive arthritis, among others.

This Guidelines summary offers a quick reference guide on screening and treatment regimens in primary care for uncomplicated and complicated infections.

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Clinical Features

• Signs and symptoms in males:
  • none—the majority are asymptomatic
  • urethral discharge
  • dysuria
  • penile irritation
  • urethral discomfort
  • urethritis (acute, persistent, recurrent)
  • balanoposthitis (in one study)
• Complications in males:
  • sexually acquired reactive arthritis
  • epididymo-orchitis
• The clinical presentation of M. genitalium urethritis is similar to other causes, and thus clinical features of acute symptomatic nongonococcal urethritis (NGU) cannot be used to determine the infective aetiology. Although the proportion of infected men that develop symptoms is unknown, this is likely to be less than 10%
• Urethral discharge may be present spontaneously or on expression, and urethritis is confirmed by demonstrating five or more polymorphonuclear leucocytes (PMNLs) per high power (x1000) microscopic field (averaged over five fields with the greatest concentration of PMNLs) on a smear obtained from the anterior urethra
• It is possible that sexually acquired reactive arthritis may occur as a result of M. genitalium infection. An association with epididymo-orchitis is possible, but current data are lacking to support an association with prostatitis. M. genitalium has been demonstrated at high prevalence in rectal samples from men who have sex with men (MSM; particularly HIV-positive MSM)
• Signs and symptoms in females:
  • none—the majority are asymptomatic
  • dysuria
  • postcoital bleeding
  • painful intermenstrual bleeding
  • cervicitis
  • lower abdominal pain (see Complications in females: pelvic inflammatory disease [PID])
• Complications in females:
  • PID
  • tubal factor infertility (uncertain association)
  • sexually acquired reactive arthritis
  • preterm delivery
• Individuals with cervicitis due to M. genitalium frequently have no symptoms at all. If present, symptoms are nonspecific, with the most common symptom being postcoital bleeding. Although the proportion of infected women that develop symptoms is unknown, this is likely to be less than 5%
• Examination is frequently normal, but on speculum examination the presence of mucopurulent cervical discharge, cervical friability, and elevated numbers of PMNLs on cervical sample Gram staining are suggestive of infection
• Clinical signs and symptoms of M. genitalium-associated PID are similar to, and indistinguishable from, PID due to Chlamydia trachomatis.

Recommendations for Testing

Based on Symptoms

• The British Association for Sexual Health and HIV (BASHH) recommends testing for M. genitalium infection in people with NGU
• BASHH recommends testing for M. genitalium infection in people with signs and symptoms suggestive of PID
• Consider testing for M. genitalium infection in people with signs or symptoms of mucopurulent cervicitis, particularly postcoital bleeding
• Consider testing for M. genitalium infection in people with epididymo-orchitis
• Consider testing for M. genitalium infection in people with sexually acquired proctitis.

Based on Risk Factors

• BASHH recommends testing current sexual partners of persons infected with M. genitalium
• Asymptomatic individuals with confirmed chlamydia and/or gonorrhoea infection should not be routinely tested for M. genitalium.

Diagnosis

• It is recommended that all M. genitalium-positive specimens should be tested for macrolide resistance-mediating mutations. In the absence of local resistance testing, the Public Health England (PHE) reference laboratory offers a molecular macrolide and fluoroquinolone susceptibility genotyping assay for specimens positive for M. genitalium.

Specimen Collection

Men

• First-void urine (FVU) is the most sensitive specimen type (sensitivity 98–100%). FVU has been shown to be more sensitive than urethral swabs.

Women

• Most studies suggest that in women, vulvovaginal swabs are the most sensitive specimen, followed by endocervical swabs. Using both vaginal and endocervical swabs increases the sensitivity further (sensitivity using a polymerase chain reaction assay: vaginal 85.7%; endocervical 74.3%; combined 95.7%).

Considerations for People Following Gender Reassignment Surgery

• There are a paucity of data concerning M. genitalium infection in individuals following gender reassignment surgery. It is therefore difficult to recommend an optimal specimen type, but this should be guided by sexual history and symptoms. For more detail, clinicians should refer to the BASHH standards for trans and non-binary people document.

Recommendations

• BASHH recommends first-void urine as the specimen of choice in cisgender men
• BASHH recommends vaginal swabs (clinician- or self-taken) as the specimen of choice in cisgender women
• BASHH recommends that, where possible, all M. genitalium-positive specimens should be tested for macrolide resistance-mediating mutations.

Window Period

• There are no data on the incubation period for M. genitalium, or on the likely window period before a laboratory test becomes reliably positive. However, it is likely that sensitive tests will detect early infection.

Management

General Advice

• Patients should be given a detailed explanation of their condition with particular emphasis on the long-term implications for the health of themselves and their partner(s). This should be reinforced with clear and accurate written information. A patient information leaflet for M. genitalium can be found on the guidelines page of the BASHH website
• Patients should be advised to abstain from sexual intercourse until 14 days after the start of treatment, and until symptoms have resolved. Where azithromycin has been used, this is especially important because of its long half-life, and is likely to reduce the risk of selecting/inducing macrolide resistance if the patient is re-exposed to M. genitalium. BASHH recommends a test of cure (TOC) should be performed in all patients.

Treatment of Uncomplicated Urogenital Infection (Urethritis, Cervicitis)

• See Algorithm 1 for a suggested treatment pathway for men presenting with NGU who subsequently test positive for M. genitalium.

Algorithm 1: Suggested Treatment Pathway for Men Presenting with Non-gonococcal Urethritis Who Subsequently Test Positive for M. Genitalium

Recommended Regimens (Uncomplicated Infections)

• Doxycycline 100 mg twice daily for 7 days followed by azithromycin 1 g orally as a single dose, then 500 mg orally once daily for 2 days where organism is known to be macrolide-sensitive or where resistance status is unknown
• Moxifloxacin 400 mg orally once daily for 10 days if organism known to be macrolide-resistant or where treatment with azithromycin has failed.

Treatment of Complicated Urogenital Infection (PID, Epididymo-orchitis)

• There are few studies examining the efficacy of extended azithromycin regimens in the treatment of PID and epididymo-orchitis caused by M. genitalium. Given the need for prompt and effective treatment in complex STI syndromes, patients with confirmed M. genitalium infection, or who have a partner who has tested positive for M. genitalium, should be given moxifloxacin as a 14-day regimen.

Recommended Regimens (Complicated Infection)

• Moxifloxacin 400 mg orally once daily for 14 days.

Partner Notification

• Only current partner(s) (including non-regular partners where there is likely to be further sexual contact) should be tested and treated if positive. This is to reduce the risk of reinfection to the index patient. Partners should be given the same antibiotic as the index patient unless there is available resistance information to suggest otherwise.

Alternative Regimens

• Very little evidence exists for the effectiveness of the following regimens but they may be considered:
  • doxycycline 100 mg twice daily for 7 days, then pristinamycin 1 g orally 4 times daily for 10 days
  • pristinamycin 1 g orally 4 times daily for 10 days
  • doxycycline 100 mg orally twice daily for 14 days
  • minocycline 100 mg orally twice daily for 14 days.

Rectal Infection

• This should be managed in the same way as urogenital infection. For severe proctitis, a longer course of moxifloxacin (14 days) may be considered.

Sourcing of Unlicensed Products

• Pristinamycin is not currently available in the UK and must be imported against a prescription. The cost of importing medicines can be high and availability is inconsistent. A Medicines and Healthcare products Regulatory Agency register of licensed wholesalers who can import medicines without a UK marketing authorisation is available. At the time of writing, pristinamycin was available from several wholesalers with a lead time of 2–3 weeks.

Pregnancy and Breastfeeding

Pregnancy

• Data on M. genitalium and its association with adverse pregnancy outcomes are limited; however, it has been associated with a small increased risk of preterm delivery and spontaneous abortion. Azithromycin use during pregnancy is unlikely to increase the risk of birth defects or adverse pregnancy outcomes
• A 3-day course of azithromycin can be used for uncomplicated M. genitalium infection detected in pregnancy
• The use of moxifloxacin in pregnancy is contraindicated
• In women with likely macrolide resistance, or with upper genital tract infection in pregnancy, options are limited
• Although doxycycline is considered safe for use in the first trimester by the US Food and Drug Administration, the British National Formulary advises against its use in all trimesters
• There are no data regarding the use of pristinamycin in pregnancy
• An informed discussion should be had with the pregnant woman around the risks associated with the use of these medicines in pregnancy and the risks of adverse outcomes associated with M. genitalium infection, and, where possible, treatment should be delayed until after pregnancy.

Breastfeeding

• Very low levels of azithromycin are detected in breast milk, and systemic exposure in infants does not exceed that observed when azithromycin is administered for treatment, therefore risk is considered to be low. Infants should be monitored for possible side effects due to effects on the gastrointestinal flora, including diarrhoea and candidiasis
• Doxycycline is excreted into breast milk and is contraindicated in nursing mothers due to the risk of tooth discolouration and effects on bone growth
• Use of moxifloxacin is contraindicated during breastfeeding
• Pristinamycin is contraindicated during breastfeeding due to its side effect profile.

Adverse Events

• Azithromycin, doxycycline, moxifloxacin, and pristinamycin can all cause gastrointestinal problems including nausea, but symptoms are most frequently reported with doxycycline and azithromycin doses over 1 g
• Caution should be taken when prescribing azithromycin or moxifloxacin to patients already on medications which may prolong the QT interval
• The European Medicines Agency committee has recommended that the use of fluoroquinolone antibiotics should be restricted following a review of their disabling and potentially long-lasting side effects
• Healthcare professionals should advise patients to stop treatment with a fluoroquinolone antibiotic at the first sign of side effects involving muscles, tendons, bones, or the nervous system. The only absolute contraindication to moxifloxacin is known hypersensitivity to this class of drugs. Hepatotoxicity has been reported, but is very rare (less than one in 10,000).

HIV

• Treatment of M. genitalium in HIV-positive individuals is the same as that for HIV-negative individuals.

Test of Cure and Follow Up

• TOC is vital in ensuring microbiological clearance of infection and is recommended for all patients with confirmed M. genitalium, even if the infection was initially sensitive to macrolides, to detect resistance which may have emerged following treatment
• Persistence of M. genitalium has been demonstrated in the absence of symptoms in men treated for NGU. This occurs in about 10–20% of men treated with doxycycline, but is not associated with development of antimicrobial resistance. Persistence of M. genitalium following treatment with azithromycin and moxifloxacin is strongly associated with antimicrobial resistance
• BASHH recommends that all patients should attend for a TOC 5 weeks (and no sooner than 3 weeks in order to avoid false negative results) after the start of treatment to ensure microbiological cure and to help identify emerging resistance
• Treatment failures should be reported to the UK Health Security Agency.

Auditable Outcome Measures

• New cases of M. genitalium should have Sexual Health and HIV Activity Property Type code 'C16' submitted to the Genitourinary Medicine Clinical Activity Dataset (performance standard 97%)
• Individuals treated for M. genitalium should have a TOC at least 5 weeks after the start of treatment (performance standard 97%)
• Cases of confirmed treatment failure by positive TOC should be reported to the UK Health Security Agency
• Individuals should be provided with written information about their diagnosis and management (performance standard 97%)
• Partner notification should be performed and documented according to the BASHH statement on partner notification for sexually transmissible infections (performance standard 97%).

Footnotes

[A] Given that most individuals will have had doxycycline as first-line treatment for uncomplicated infection, a repeat course is unnecessary once the M. genitalium positive result is known. Azithromycin should be given immediately after doxycycline, and ideally within 2 weeks of completing doxycycline. If this is not possible, the course of doxycycline should be repeated prior to giving azithromycin.

[B] Treatment failure is defined as persistent symptoms following treatment, or a positive test of cure taken 5 weeks post-treatment.

[C] Prior treatment with doxycycline will reduce M. genitalium load, and has been demonstrated to be of benefit if administered prior to extended azithromycin and also pristinamycin treatment which is only 75% effective as monotherapy.