Sexually transmitted infection by Mycoplasma genitalium: A short review
How to cite this article: Harish S. Sexually transmitted infection by Mycoplasma genitalium: A short review. J Skin Sex Transm Dis 2021;3(1):46-50.
Mycoplasma genitalium is identified as a pathogen causing sexually transmitted infection. Difficulty to culture the organism has been a major obstacle in understanding more about the pathogenesis. Lack of facility to diagnose the disease in many centers has led to syndromic management. Widespread treatment of asymptomatic individuals who test positive for the organism and syndromic management have resulted in emergence of drug-resistant strains.
Recent years have seen much interest in research and knowledge about Mycoplasma genitalium (M. genitalium) as a pathogen capable of causing sexually transmitted infection (STI). Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, published in 2015, have placed M. genitalium under emerging issues.
About 15%–20% of non-gonococcal urethritis (NGU) cases, 20%–25% of non-chlamydial NGU, and about 30% of recurrent or persistent urethritis are considered to be caused by M. genitalium. In most settings, its prevalence is more than that of Neisseria gonorrhoeae but less common than that of Chlamydia trachomatis. Although often the sole pathogen isolated, its coinfection with C. trachomatis is not uncommon. M. genitalium is suggested as an independent risk factor for the acquisition of human immunodeficiency virus (HIV) infection. Thus, it becomes essential for the clinicians to have awareness about the clinical presentation, diagnosis, and management guidelines of M. genitalium infection.
M. genitalium is the smallest known self-replicating organism with a genome size of only 580 Kb. It belongs to the class Mollicutes (meaning soft skin). M. genitalium lacks a cell wall which has provided the organism inherent resistance against antibiotics such as beta-lactams and penicillins that target cell wall synthesis. This flask-shaped organism has a slightly curved terminal organelle. Ability for adhesion, gliding motility, and cell invasion aid it in pathogenesis. The organism is small enough to penetrate the surface of the agar medium, hence when viewed microscopically from above, the colonies give the characteristic “fried egg” appearance. The colonies appear as “flying saucers” when looked obliquely from beneath with adequate lighting.
The organism has been detected in the genitourinary, rectal, and respiratory tract specimens, but is very rare in the throat. It was first isolated in 1981 from the urethral samples of two men presenting with NGU. Originally, it was isolated from a medium from which thallous acetate had been omitted. Thallous acetate is a chemical that is often incorporated in media for mycoplasma. This led to the conclusion that the organism is susceptible to thallous acetate.
Younger age group, smoking, dark skin phenotype, and multiple partners are the common risk factors for acquiring this infection.[7-9] Most common route of transmission is by genital-genital contact. Penile-anal transmission has also been reported. Oral sex is not considered to be significant in transmission.[11-13]
CLINICAL SIGNS AND SYMPTOMS
Majority of males infected with M. genitalium remain asymptomatic. It is possible that <10% of males develop symptoms due to M. genitalium, though the exact proportion of those who develop symptoms remains unknown. Urethral discharge, dysuria, urethral discomfort, or penile discomfort are seen in some of the affected men. Features of acute, recurrent, or persistent urethritis may be present. Anagrius et al. reported an association between M. genitalium and balanoposthitis. It can also be associated with complications such as sexually acquired reactive arthritis (SARA) and epididymitis.[4,13,15] There are not enough data regarding the incidence of prostatitis in patients with M. genitalium. In patients with proctitis, higher bacterial load of M. genitalium was noted, but its exact role in disease causation needs further elucidation.
In females, again majority of the infected, remain asymptomatic. Although the exact proportion is not known, it is believed that <5% of infected women develop symptoms.[17,18] Post-coital bleeding, dysuria, intermenstrual bleeding (which can be painful), cervicitis, and lower abdominal pain are the manifestations reported in symptomatic cases. Cervicitis most often presents as post-coital bleeding. M. genitalium infection in females may be associated with complications such as pelvic inflammatory disease (PID), SARA, and preterm delivery.
WHEN TO TEST PATIENTS FOR M. genitalium?
Testing for M. genitalium is recommended in men with NGU. It is recommended to consider testing for M. genitalium in patients with epididymitis and sexually acquired proctitis. In women, testing is recommended in patients with signs and symptoms of PID. Testing must be considered in people with signs or symptoms of mucopurulent cervicitis, especially those manifesting post-coital bleeding.
Gram stain analysis of genital secretions cannot detect M. genitalium since it lacks a cell wall. Culture is not the preferred diagnostic technique since the organism is very slow growing (about 6 months in culture) and fastidious in its growth requirements. Nucleic acid amplification tests that detect specific deoxyribonucleic acid or ribonucleic acid of M. genitalium in samples are the test of choice. Due to a high rate of macrolide resistance, it would be ideal to test all M. genitalium positive specimens for macrolide resistance as well.
In men, first void urine is the most sensitive specimen, which is more sensitive than urethral swabs.[21-23] In women, vulvovaginal swabs (self-taken or clinician taken) are the most sensitive followed by the endocervical swabs.[22,24,25] Exact information regarding the incubation period or window period before which a laboratory test becomes positive is lacking.
Management of patients involves detailed explanation of the condition, and advice to abstain from sexual intercourse for 14 days from the start of the treatment or till the resolution of symptoms, whichever is later.[13,26,27]
Macrolide-resistant M. genitalium is becoming more common worldwide. The prevalence of macrolide-resistant strains ranges from 30% to 100%. Doxycycline as monotherapy [Table 1] has a low eradication rate for M. genitalium, but it is seen that treatment with doxycycline followed by an extended azithromycin regimen (an initial 500 mg dose followed by 250 mg daily for 4 days) can improve the success of treatment.[13,26,27] This could be because doxycycline reduces the load of the organism, thus bringing down the risk of macrolide resistance [Table 1].[13,26,27]
|For uncomplicated infections|
|If macrolide sensitivity is unknown or if the organism is known to be macrolide sensitive – doxycycline 100 mg twice daily for 7 days followed by azithromycin 500 mg stat dose followed by 250 mg daily for 4 days|
|Infection by macrolide-resistant organism or in cases of treatment failure|
|Moxifloxacin 400 mg orally once daily for 10 days
For complicated cases (e.g., epididymitis, severe proctitis, and pelvic inflammatory diseases) – moxifloxacin 400 mg orally once daily for 14 days
|Alternative treatment regimens|
|Doxycycline 100 mg twice daily for 14 days
Pristinamycin 1 g orally 4 times daily for 10 days
Doxycycline 100 mg twice daily for 7 days followed by pristinamycin 1 g 4 times daily for 10 days
Minocycline 100 mg twice daily for 14 days
As doxycycline is used as first-line drug for uncomplicated NGU, a repeat treatment with doxycycline is not required if patient tests positive for Mycoplasma genitalium after standard treatment for NGU. Azithromycin should be given immediately after doxycycline and preferably within 2 weeks of completing doxycycline. NGU: Non-gonococcal urethritis
Moxifloxacin has been found to be very effective in Europe, but resistance seems to be increasing in Asia–Pacific region to the drug.[29,30] Therefore moxifloxacin as the first line treatment is not recommended. Ten days are the recommended duration of optimal treatment.
Pristinamycin, a streptogramin, that binds the 50S subunit of the bacterial ribosome is found useful against M. genitalium. The different regimens prescribed are 1 g 2 times a day or 1 g 4 times a day or a combination therapy of 1 g 3 times a day with doxycycline for 10 days.
Although the mechanism of action remains unknown, minocycline at 100 mg twice a day for 14 days is found useful in treating M. genitalium infections that failed to respond to doxycycline and showed both macrolide and quinolone resistance mutations.
Three-day course of azithromycin can be used for uncomplicated M. genitalium infection. In pregnant women with macrolide resistance or with upper genital tract involvement, treatment options are limited. Moxifloxacin and doxycycline are contraindicated in pregnancy. There are no data regarding the safety of pristinamycin in pregnancy. As the amount of azithromycin detected in breast milk is very low, it is considered to be of low risk in lactation. An increased risk of pyloric stenosis has been reported in breastfed infants of mothers who had taken macrolides during the post delivery period of 0-13 days. Doxycycline, moxifloxacin, and pristinamycin are contraindicated in lactation.
Treatment of M. genitalium in HIV-positive patients is the same as that for HIV-negative individuals.
Treatment of asymptomatic individuals
There is no evidence to recommend screening and treatment of asymptomatic individuals for M. genitalium. This is based on the knowledge that there will be spontaneous clearance of infection in many of the affected. On the contrary, treatment of asymptomatic individuals may increase the risk of the organism acquiring antimicrobial resistance.
Asymptomatic partners of patients who tested positive for M. genitalium should be tested and when found positive, should be treated using the same treatment regimen. Testing of current partners is recommended so as to avoid reinfection in index case. This is contrary to the partner notification advised for most other STI pathogens, where contact tracing and treatment are offered to all sexual contacts of previous 3 months to prevent transmission in the community.
Test of cure is recommended for all patients to confirm clearance of the organism. If M. genitalium is detected after treatment with azithromycin or moxifloxacin, it strongly indicates antimicrobial resistance.[37,38] The time taken for eradication of the organism after treatment is variable. One study that used polymerase chain reaction to detect the organism reported 96% eradication within 8 days after treatment with azithromycin, but the same authors noted that after a period of negative results, the patient showed resistant strains. This suggested that test of cure should be delayed after treatment. Test of cure is recommended for all patients and should be performed 5 weeks after the start of treatment. However, others have questioned this recommendation stating that the treatment should aim at clinical cure, rather than microbiological eradication. It is argued that an asymptomatic infection may be nonpathogenic and attempt at microbiological eradication may lead to overtreatment.
When facility is not available for diagnosing M. genitalium infection, an empirical treatment may be started in patients with persistent or recurrent NGU, or in those with PID, who show lack of response to treatment within 7–10 days.
As per current knowledge, the most common cause of persistent or recurrent NGU (especially following treatment with doxycycline) is M. genitalium. The possibility of disease caused by M. genitalium should be considered in PID cases not responding to treatment since the recommended treatment regimens for PID advise antibiotics that are ineffective against M. genitalium.
It is advised that azithromycin 1 g orally should be given to men who manifest recurrent or persistent NGU after treatment with doxycycline. Higher doses of azithromycin were not found effective in such patients; hence, those who fail to respond to 1 g azithromycin should receive retreatment with moxifloxacin. Moxifloxacin 400 mg/day for 14 days is the recommended treatment for PID patients who do not respond to standard treatment.
ADVERSE EFFECTS OF DRUGS USED IN TREATMENT
Most common side effects with azithromycin, doxycycline, moxifloxacin, and pristinamycin are gastrointestinal problems.[40,41] Azithromycin and moxifloxacin can prolong QT interval, so one must be cautious when prescribing it to patients who are on medications that can prolong QT interval. Fluoroquinolone antibiotics can cause side effects affecting muscles, tendons, bones, or nervous system.
Additional research can give valuable information on the disease pathogenesis and may help to improve the management of infections due to M. genitalium. In resource-poor settings, where diagnostic facilities are not available, patients who fail first-line treatment for urethritis, cervicitis, and PID should receive treatment for M. genitalium infection.
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