Mycoplasma genitalium

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Mycoplasma genitalium (MG) is a sexually transmitted bacterium only detectable by nucleic acid amplification tests (NAAT). It causes urethritis in men, cervicitis in women, and (often asymptomatic) rectal infection. It is associated with pelvic inflammatory disease (PID) and is a possible cause of preterm delivery, spontaneous abortion and tubal infertility.
DIAGNOSIS
Most laboratories now offer NAAT testing for M. genitalium or can forward to others such as Molecular Microbiology at the Royal Women’s Hospital or the Victorian Infectious Diseases Reference Laboratory. Some NAA tests also detect a mutation conferring resistance to macrolides such as azithromycin.

Men
In men, a first void urine specimen appears more sensitive than a urethral swab. A urine specimen for MG should be performed in all men with non-gonococcal urethritis (NGU). See urethritis guideline.

Women
In women, a vaginal swab is the most sensitive specimen but first void urine or cervical swabs can be used. Women who present with cervicitis or PID should be tested for MG. See vaginal discharge guideline.

Men who have sex with men (MSM)
Rectal infection is common and MG has an uncertain association with proctitis.

Asymptomatic peopleSexual contacts of MG, particularly those in a continuing relationship with a symptomatic case, should be offered testing. MSM require anorectal swabs. Throat swabs are unnecessary as pharyngeal infection is considered rare. Screening other asymptomatic individuals for M. genitalium is currently not recommended.

TREATMENT
In 2016-2017 macrolide resistance mutations were detected in approximately 80% of MSM and 50% of heterosexual men and women infected with MG at Melbourne Sexual Health Centre (MSHC). Infections susceptible to azithromycin develop detectable resistance in 10 – 20% of cases treated with azithromycin, presumably selected during treatment. To improve treatment efficacy and reduce selection of resistance MSHC is investigating a non-PBS treatment protocol supported by limited data1 - see Rationale, below.

MG infections treated with azithromycin on the same day as the MG test may be cured but confirm this with a test of cure at least three weeks later. If treatment fails, resistance is almost certain, particularly if reinfection is unlikely. Clinicians with no access to resistance testing can assume resistance in azithromycin treatment failures and, at least in Melbourne, in MSM.

To avoid the selection of macrolide resistance, MSHC treats urethritis, cervicitis and proctitis with one week of doxycycline 100mg bd, instead of azithromycin. All patients with these syndromes are tested for MG and recalled if positive. Other MG-infected patients (eg sexual partners) are also pre-treated with doxycycline which lowers the bacterial load,1 increasing the likelihood of cure with a second antibiotic.2-4 Doxycycline alone only cures 30% of infections.5

For MG infections known or suspected to be macrolide-susceptible

  • doxycycline 100mg bd, 7 days, followed immediately by
  • azithromycin 1g stat, then 500mg daily for another three days (2.5g total)
For MG infections known or suspected to be macrolide resistant (MG in MSM, persisting symptoms >7 days, positive MG result >21 days after azithromycin, MG resistance mutation detected) use
  • doxycycline 100mg bd, 7 days, followed immediately by
  • moxifloxacin 400mg daily for seven days

Moxifloxacin is not approved by the Therapeutic Goods Administration (TGA) for this infection and may cause significant side-effects including diarrhoea or tendonitis. We recommend discussing this with patients. Pharmacies typically charge over $70 for five tablets. There are limited efficacy data and no data for treatment courses of less than seven days.6

FOLLOW-UP
Test of cure is essential in managing all MG infections because of the risk of persisting, asymptomatic, resistant infection. The ideal time is three weeks (minimum two) after starting the definitive second antibiotic. If azithromycin has been prescribed and symptoms are improving it is reasonable to wait and perform a test of cure. If symptoms have persisted or rebounded to similar intensity, treatment failure due to resistance is likely, but reinfection is also possible.

Sexual partners
Testing, and treating infected partners is recommended, particularly in a continuing relationship. Given the high prevalence of macrolide resistance and need for moxifloxacin in cases with resistance, discuss with patients both the benefits of treatment and the risk of uncommon but serious side effects. Infection rates in contacts are 40–50% in women and MSM (mostly rectal infection) and 30% in heterosexual men.
 
M.genitalium associated PID
Routine PID treatment is not likely to adequately treat Mg-associated PID and moxifloxacin is recommended for 14 days. See MSHC treatment guideline on PID. 

M.genitalium in pregnancy
Azithromycin is category B1 and can be prescribed in pregnancy. If a patient is pregnant and considered at risk of resistant M.genitalium infection this case should be discussed with a sexual health physician and pristinamycin may be recommended.

Pristinamycin
Resistance to fluoroquinolones (eg moxifloxacin) was detected in 14% of infections in Melbourne in 2012-137 and so moxifloxacin treatment-failures are expected. Pristinamycin may be effective when quinolones have failed or cannot be used. It has been used at MSHC at a dose of 1g qid or (combined with doxycycline 100mg bd) 1g tds for 10 days and appears to cure 70 - 80% of macrolide-resistant infections.8 This is available through hospital pharmacies, using the Special Access Scheme of the TGA.

Rationale
This treatment protocol is a response to the finding of macrolide resistance mutations in two-thirds of our patients since we began routine resistance testing in 2016 and the further selection of macrolide resistance in at least 10% of apparently susceptible cases. We no longer use azithromycin for NGU, cervicitis and proctitis because of the increasing macrolide resistance in MG, gonorrhoea and syphilis. In line with recent changes in the UK and European guidelines we have switched to doxycycline first line instead of 1g azithromycin.

The protocol is only supported by limited evidence. A preliminary evaluation of an otherwise identical protocol, which used sitafloxacin (100mg bd for 7 days) instead of moxifloxacin, found that >90% of infections in both treatment groups were cured.1 Doxycycline lowered bacterial load in most cases. Several studies show that low load infections are more likely to be cured.2-4 Sweden, which uses doxycycline to treat non-gonococcal urethritis and 1.5g of azithromycin over five days, has low rates of azithromycin failure and resistance.5

  1. Read TRH, Fairley CK, Jensen JS, et al. Improved outcomes following resistance-guided treatment of Mycoplasma genitalium infection. International Society for Sexually Transmitted Diseases Research. Rio de Janiero2017.
  2. 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2015;60:1228-36.
  3. Guschin A, Ryzhikh P, Rumyantseva T, Gomberg M, Unemo M. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin. BMC infectious diseases 2015;15:40.
  4. Read TRH, Fairely CK, Tabrizi S, Bissessor M, Vodstrcil L, Chow EPF, Grant M, Danielewski J, Garland SM, Hocking JS, Chen MY, Bradshaw CS. Azithromycin 1.5g over five days compared to 1g single dose in urethral Mycoplasma genitalium: impact on treatment outcome and resistance Clinical Infectious Diseases 2016.
  5. Jensen JS, Bradshaw C. Management of Mycoplasma genitalium infections - can we hit a moving target? BMC infectious diseases 2015;15:343.
  6. Li Y, Le WJ, Li S, Cao YP, Su XH. Meta-analysis of the efficacy of moxifloxacin in treating Mycoplasma genitalium infection. International journal of STD & AIDS 2017:956462416688562.
  7. Murray GL, Bradshaw CS, Bissessor M, et al. Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium. Emerg Infect Dis 2017;23:809-12.
  8. Bradshaw CS, Read TRH, Fairley CK, Jensen J, Danielewski J, Tabrizi S. Efficacy of pristinamycin for treatment resistant Mycoplasma genitalium. Australasian Sexual Health Conference. Adelaide2016.

 

Disclaimer
The content of these treatment guidelines is for information purposes only. The treatment guidelines are generic in character and should be applied to individuals only as deemed appropriate by the treating practitioner on a case by case basis. Alfred Health, through MSHC, does not accept liability to any person for the information or advice (or the use of such information or advice) which is provided through these treatment guidelines. The information contained within these treatment guidelines is provided on the basis that all persons accessing the treatment guidelines undertake responsibility for assessing the relevance and accuracy of the content and its suitability for a particular patient. Responsible use of these guidelines requires that the prescriber is familiar with contraindications and precautions relevant to the various pharmaceutical agents recommended herein.

Last Updated August 2017