Mycoplasma genitalium: Challenges in Diagnosis and Treatment

The Centers for Disease Control and Prevention (CDC) listed Mycoplasma genitalium bacterial infection as an “emerging issue” in its Sexually Transmitted Diseases Treatment Guidelines in 2015.^1,2 M genitalium was only first identified in the 1980s and is increasingly recognized as an important cause of several sexually transmitted infections (STIs), such as urethritis in men and cervicitis in women.¹ In fact, M genitalium infection is responsible for more STIs than Neisseria gonorrhoeae and is the second-most prevalent STI next to Chlamydia trachomatis infection. Despite its widespread prevalence, however, M genitalium infection can be difficult to diagnose and treat.³

Infectious Disease Advisor spoke with Oluwatosin Jaiyeoba Goje, MD, from the Ob/Gyn & Women’s Health Institute of Cleveland Clinic in Ohio, and Amesh Adalja, MD, spokesman for the Infectious Diseases Society of America and Senior Associate with Johns Hopkins Center for Health Security in Baltimore, Maryland, about challenges in the diagnosis and management of M genitalium infection.

An Emerging STI

M genitalium infection is a ubiquitous cause of STIs worldwide, with prevalence rates ranging from 0.4% in young adults in the United States to 4.5% in The Netherlands. Up to 6.3% of patients at a sexually transmitted diseases (STD) clinic in Sweden were found to have M genitalium infection. Although prevalence rates differ between countries, M genitalium is the most common cause of STIs, ranking only second to C trachomatis in prevalence.³

“The prevalence of M genitalium is especially concerning because most people infected with the bacteria don’t even know they have it,” Dr Goje said. “Symptoms could be non-specific and non-existent and, when left untreated, M genitalium infection can produce devastating health problems including urethritis, cervicitis, and pelvic inflammatory diseases.”

Even when patients are symptomatic, clinicians may not necessarily know to look for M genitalium. “Clinicians are less familiar with M genitalium infection than they are with other, more common STIs that they have experience treating or learned about in medical school,” Dr Adalja said. “But M genitalium has a high enough prevalence in certain contexts that it’s something we don’t want to ignore.”

Diagnostic Techniques and Challenges

According to Dr Adalja, M genitalium infection should be considered in men with symptoms of urethritis — similar to the symptoms observed in chlamydia and gonorrhea. “M genitalium is the second most common cause of urethritis, and it has been definitively studied in men. You would especially want to test men who didn’t get better after the first course of antibiotics, because M genitalium is frequently resistant to antibiotics that are commonly used to treat STIs,” Dr Adalja said.

Dr Goje also suggests testing for M genitalium in women with persistent symptoms of cervicitis, particularly in women who have not responded to empiric antibiotic therapy for chlamydia and gonorrhea and have tested negative for these pathogens.

Testing for M genitalium, however, can be cumbersome and time-consuming because M genitalium is a slow-growing organism.³ “Isolating and culturing M genitalium is not feasible when there is a need to institute immediate antimicrobial therapy,” Dr Goje said.

“While there is no FDA-approved test for M genitalium, nucleic acid amplification test (NAAT) is the preferred technique,” Dr Goje said. NAAT uses polymerase chain reaction (PCR) and can be performed on multiple sample types, including urethral, vaginal, and cervical swabs; urine; and endometrial biopsies.

However, NAAT for diagnosing M genitalium uses assays that were developed for the research setting and, as a result, NAAT is only available in reference labs — usually at large university hospitals. “If you’re in a small hospital, you have to know where you can get the testing done, and which hospitals are doing it in research settings,” Dr Adalja said. “It’s not something that you would find readily available.”

Management and Antimicrobial Resistance

Significant antimicrobial resistance presents a major challenge to the treatment of M genitalium infection. Because M genitalium lacks a cell wall, antibiotics targeting cell wall biosynthesis, such as beta lactams (eg, penicillins and cephalosporins), are ineffective against this organism, Dr Goje said. 

According to Dr Adalja, patients with urethritis commonly receive an empiric course of doxycycline, which covers C trachomatis but is associated with high treatment failure rates for M genitalium infection. “Over half of patients with M genitalium who are treated with doxycycline may have a microbiological failure,” he said.

Dr Goje noted that patients who have not responded to an initial course of doxycycline often require a second round of antibiotic treatment, usually consisting of azithromycin for at least 5 days. However, up to 50% of patients with M genitalium infection exhibit resistance to azithromycin. In cases of azithromycin failure, moxifloxacin 400 mg daily for 7 to 14 days is the preferred antibiotic regimen. “Cure rates with moxifloxacin are 100% in initial reports, although more studies are needed,” Dr Goje said.

To prevent further development of antimicrobial resistance in M genitalium, clinicians need to avoid using inappropriate antibiotics—such as doxycycline — as initial treatment, Dr Adalja said. “I think that the key to optimizing treatment for M genitalium is to increase awareness among clinicians that this organism may be causing their patient’s STI symptoms. Many clinicians who are not in the infectious diseases or STI world probably don’t know much about M genitalium and its role in STI. As a result, they may inadvertently continue to prescribe the wrong antibiotic.”

Challenges in making the diagnosis of M genitalium infection in the first place pose one of the most important barriers to successful treatment, according to Dr Goje. “We can’t effectively treat what we cannot diagnose,” she said. “Sometimes we have no choice but to empirically treat based on signs and symptoms and elimination of other known causes of urethritis and cervicitis.”

References

1. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR3):1-137.
2. Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. Nat Rev Urol. 2017;14(3):139-152.
3. Munoz JL, Goje OJ. Mycoplasma genitalium: an emerging sexually transmitted infection. Scientifica (Cairo). 2016;2016:7537318. doi:10.1155/2016/7537318