What is Ureaplasma?
Ureaplasma is a genus of cell wall-deficient bacteria that colonizes the human urogenital tract, comprising two species—Ureaplasma urealyticum and Ureaplasma parvum—with U. urealyticum recognized as a pathogen in nongonococcal urethritis while U. parvum is generally considered non-pathogenic. 1, 2
Microbiological Characteristics
- Ureaplasma species lack a cell wall, which makes them inherently resistant to beta-lactam antibiotics and difficult to culture using standard microbiological methods 2, 3
- The organism possesses 14 known serotypes divided into two biovars: U. parvum (biovar 1) and U. urealyticum (biovar 2) 2
- Key virulence factors include urease enzyme, phospholipases A and C, IgA protease, and the Multiple Banded Antigen (MBA) which elicits host antibody responses 2
Clinical Significance and Pathogenicity
Established Pathogenic Role
- U. urealyticum, but NOT U. parvum, is recognized as an etiological agent in nongonococcal urethritis (NGU) 1, 4
- U. urealyticum accounts for 15-25% of NGU cases in males and is associated with cervicitis and pelvic inflammatory disease in females 1
- A meta-analysis demonstrated that U. urealyticum and Mycoplasma hominis strains were associated with male infertility, while U. parvum and M. genitalium were not 1
Colonization vs. Infection—A Critical Distinction
- Culture or NAATs for Ureaplasma are NOT recommended due to high prevalence of colonization in asymptomatic, sexually active people 1
- The presence of Ureaplasma in the urogenital tract often represents commensal colonization rather than pathogenic infection 1
- Treatment should only be initiated when there are objective signs of urethritis (≥5 polymorphonuclear leukocytes per high-power field on urethral smear) or symptomatic urethritis (discharge, dysuria, urethral pruritus) 4
Clinical Manifestations
Urogenital Infections
- In men: nongonococcal urethritis, epididymitis, prostatitis, and potential contribution to infertility 2, 5
- In women: cervicitis, pelvic inflammatory disease, and adverse pregnancy outcomes including preterm labor 2
- Symptoms include mucopurulent or purulent urethral discharge, dysuria, and urethral pruritus, though many infections are asymptomatic 1
Pregnancy and Neonatal Complications
- Ureaplasma infection produces cytokines in amniotic fluid that can initiate preterm labor 2
- Associated with chronic lung disease and retinopathy of prematurity in newborns 2
Invasive Infections in Immunocompromised Patients
- Immunosuppressed patients (including those on rituximab or with HIV) are at increased risk of invasive Ureaplasma infections including intra-abdominal abscesses, empyema, suppurative arthritis, and renal stones 2, 3
- Ureaplasma may act as a cofactor in AIDS pathogenesis 2
Diagnostic Approach
- Culture and PCR are the mainstay of diagnosis, with commercial assays now available with improved turnaround time 2
- 16S rRNA PCR assays can detect Ureaplasma when conventional cultures are negative 3
- The organism's lack of cell wall makes standard culture difficult and time-consuming 3
- Diagnosis should be reserved for symptomatic patients or those with objective evidence of urethritis, not for screening asymptomatic individuals 1, 4
Treatment Principles
When to Treat
- Only treat when there are symptoms of urethritis or documented urethritis (≥5 PMNs/HPF on urethral smear) 4
- Do NOT treat asymptomatic bacteriuria unless the patient is undergoing traumatic urinary tract procedures 4
- Avoid treating based on laboratory detection alone without clinical correlation 1, 4
First-Line Treatment
- Doxycycline 100 mg orally twice daily for 7 days is the primary treatment for U. urealyticum infections 4
- For men where prostatitis cannot be excluded, consider extending treatment to 14 days 4
Alternative Regimens
- Azithromycin 1 g orally as a single dose (particularly useful for compliance concerns) 4
- Erythromycin base 500 mg orally four times daily for 7 days 1, 4
- Fluoroquinolones (levofloxacin 500 mg once daily or ofloxacin 300 mg twice daily for 7 days) 4
Critical Treatment Pitfalls
- Avoid empirical fluoroquinolone use in patients from urology departments or those who used fluoroquinolones in the last 6 months due to high resistance rates 4
- Always treat sexual partners with last contact within 30 days of symptom onset (symptomatic patients) or 60 days of diagnosis (asymptomatic patients) 4
- Resistance to macrolides, tetracyclines, and fluoroquinolones has been reported, with biovar 2 (U. urealyticum) maintaining higher sensitivity rates than biovar 1 2
Antimicrobial Resistance
- Increasing resistance to macrolides, tetracyclines, and fluoroquinolones has been documented 2, 6
- Moxifloxacin 400 mg orally once daily for 7-14 days is an option for macrolide-resistant infections 4
- Microdilution testing against azithromycin, josamycin, ofloxacin, and doxycycline is routinely performed for susceptibility determination 2