Genital Mycoplasma Infection
Genital mycoplasma infection, led by Mycoplasma genitalium (and to a lesser degree Mycoplasma hominis and Ureaplasma urealyticum), is an emerging sexually transmitted infection (STI) that is becoming increasingly troublesome. Often called the "stealth" organisms of microbiology, mycoplasmas have tiny genomes and no peptidoglycan cell wall at all. Because of this unusual biology, they are intrinsically resistant to every beta-lactam antibiotic (penicillins, cephalosporins), drugs that work by blocking cell wall synthesis.
Among the genital mycoplasmas, M. genitalium is the main culprit. It causes roughly 15–25% of nongonococcal urethritis (NGU) in men, and cervicitis, endometritis and pelvic inflammatory disease (PID) in women. Because symptoms tend to be subacute, silent or persistent, the infection is easily missed or treated with the wrong regimen. More worrying still is the worldwide spread of M. genitalium strains with mutations conferring resistance to macrolides (azithromycin) and fluoroquinolones (moxifloxacin), which makes treatment a real challenge.
At Haute-Derma, we manage genital mycoplasma infection according to the latest IUSTI/CDC recommendations: multiplex real-time PCR (NAAT) testing, genetic testing for resistance mutations, and resistance-guided sequential therapy followed by a test of cure, to prevent infertility and pelvic scarring.
Pathogenesis: A Wall-less Bacterium and How It Evades the Immune System
Unusual Structure and Built-in Antibiotic Resistance
- Mycoplasma genitalium is one of the smallest known self-replicating bacteria, only 0.2–0.3 µm across.
- Lacking a peptidoglycan cell wall, it can change shape freely and is intrinsically resistant to antibiotics that target the cell wall, such as penicillin G, ampicillin, ceftriaxone, cefixime and vancomycin.
The MgPa Adhesion Complex and Intracellular Survival
- At one end, the bacterium has a specialized tip structure carrying the adhesin MgPa (Mycoplasma genitalium protein A), which lets it cling tightly to the columnar epithelial cells of the urethra and cervix and to sperm.
- Once attached, M. genitalium can enter the host cell (a partly intracellular lifestyle), hiding from the immune system and from antibiotics in the bloodstream. It damages cells by releasing toxic by-products such as hydrogen peroxide and superoxide radicals.
Clinical Features
Men (Nongonococcal Urethritis, NGU):
- Incubation period: 1 to 3 weeks after sexual contact.
- Symptoms: a small to moderate amount of clear or slightly cloudy mucoid urethral discharge (unlike the thick yellow-green pus of gonorrhea), itching or tickling along the urethra, mild burning on urination and frequent urination.
- Persistence: symptoms often linger or keep coming back after standard treatment for gonorrhea or chlamydia.
Women (Cervicitis and Pelvic Inflammatory Disease, PID):
- More than 50–70% of infections cause no obvious symptoms.
- Signs: increased abnormal vaginal discharge, bleeding after sex (postcoital bleeding), bleeding between periods and lower abdominal pain or pressure.
- Complications: PID and salpingitis that can scar and block the fallopian tubes, a higher risk of tubal factor infertility, ectopic pregnancy and miscarriage.
The Alarming Rise of Drug-Resistant Strains
- Macrolide resistance: point mutations at position 2058 or 2059 of the 23S rRNA gene cut the cure rate of azithromycin from over 85% to below 30–40%.
- Fluoroquinolone resistance: mutations in the QRDR region of the parC and gyrA genes make moxifloxacin ineffective.
Differential Diagnosis of Urethritis / Cervicitis Pathogens
| Mycoplasma genitalium | Chlamydia trachomatis | Neisseria gonorrhoeae |
|---|---|---|
| NO cell wall | Thin cell wall | Gram-negative bacterium |
| Scant, clear or slightly cloudy mucus | Moderate, clear or cloudy-white mucus | Profuse, thick yellow/green pus |
| Mild burning, itching along the urethra | Mild to moderate burning | SEVERE PAIN ("like passing broken glass") |
How We Diagnose It at Haute-Derma
Molecular Testing by NAAT / Real-Time PCR (the Required Gold Standard):
- Because M. genitalium grows extremely slowly (culture takes 1 to 6 months) and has no cell wall to show up on a Gram stain, real-time PCR is the only reliable way to confirm the diagnosis.
- Samples: first-void urine (the first 10–20 mL, with no urination in the previous 2 hours) for men; a cervical or vaginal swab for women.
Genetic Testing for Macrolide Resistance: as soon as a sample is PCR-positive for M. genitalium, PCR-RFLP or sequencing is used to look directly for 23S rRNA mutations, so the doctor can choose the right antibiotic from the start.
Screening for Other STIs: a multiplex test checks at the same time for gonorrhea (N. gonorrhoeae), Chlamydia trachomatis, Trichomonas vaginalis, syphilis and HIV.
Sequential Therapy at Haute-Derma
Standard Sequential Regimen (IUSTI / CDC Guidelines)
- Step 1 (initial phase: reducing the bacterial load):
- Doxycycline: 100 mg by mouth twice daily for 7 consecutive days.
- Step 2 (eradication, guided by resistance testing):
- Macrolide-susceptible strain (no mutation):
- Follow straight on with azithromycin: 1 g by mouth on day 8, then 500 mg once daily on days 9, 10 and 11 (2.5 g in total).
- Macrolide-resistant strain (mutation present) OR resistance testing not available:
- Follow straight on with moxifloxacin: 400 mg by mouth once daily for 7 consecutive days (days 8 to 14).
- Macrolide-susceptible strain (no mutation):
- Moxifloxacin failure (multidrug resistance): an advanced combination of doxycycline 100 mg twice daily for 14 days PLUS sitafloxacin or pristinamycin, decided at a specialist case conference at Haute-Derma.
Partner Management and Test of Cure
- Partner management: anyone who has had sex with the patient in the past 60 days should have a PCR test and be treated with an equivalent sequential regimen, to avoid passing the infection back and forth (ping-pong infection).
- Timing of the test of cure (TOC): patients must return for a repeat real-time PCR 21 to 28 days after finishing antibiotics. Testing too early (< 21 days) can give a false-positive result from leftover DNA of dead bacteria.
