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Chlamydial, Mycoplasmal, and Ureaplasmal Mucosal Infections


Sheldon R. Morris

, MD, MPH, University of California San Diego

Last full review/revision Dec 2020| Content last modified Sep 2022
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Sexually transmitted urethritis, cervicitis, proctitis, and pharyngitis not due to gonorrhea are caused predominantly by chlamydiae and infrequently by mycoplasmas or Ureaplasma sp. Chlamydiae may also cause salpingitis, epididymitis, perihepatitis, neonatal conjunctivitis, and infant pneumonia. Untreated chlamydial salpingitis can become chronic, causing minimal symptoms but having serious consequences. Diagnosis is by culture, immunoassay for antigens, or nucleic acid–based tests. Treatment is with single-dose azithromycin or a week of ofloxacin, levofloxacin, erythromycin, or a tetracycline.

Several organisms can cause nongonococcal sexually transmitted cervicitis in women and urethritis, proctitis, and pharyngitis in both sexes. These organisms include

The imprecise term "nonspecific urethritis” can be used, but only if tests for chlamydiae and gonococci are negative and no other pathogen is identified.

Symptoms and Signs

Men develop symptomatic urethritis after a 7- to 28-day incubation period, usually beginning with mild dysuria, discomfort in the urethra, and a clear to mucopurulent discharge. Discharge may be slight, and symptoms may be mild but are frequently more marked early in the morning; then, the urethral meatus is often red and blocked with dried secretions, which may also stain underclothes. Occasionally, onset is more acute and severe, with severe dysuria, frequency, and a copious, purulent discharge that simulates gonococcal urethritis. Infection may progress to epididymitis. After rectal or orogenital contact with an infected person, proctitis or pharyngitis may develop.

Women are usually asymptomatic, although vaginal discharge, dysuria, increased urinary frequency and urgency, pelvic pain, dyspareunia, and symptoms of urethritis may occur. Cervicitis with yellow, mucopurulent exudate and cervical ectopy (expansion of the red endocervical epithelium onto the vaginal surfaces of the cervix) are characteristic. Pelvic inflammatory disease Pelvic Inflammatory Disease (PID) Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper female genital tract: the cervix, uterus, fallopian tubes, and ovaries; abscess may occur. PID may be sexually transmitted... read more (PID; salpingitis and pelvic peritonitis) may cause lower abdominal discomfort (typically bilateral) and marked tenderness when the abdomen, adnexa, and cervix are palpated. Long-term consequences of PID include ectopic pregnancy and infertility. Fitz-Hugh-Curtis syndrome (perihepatitis) may cause right upper quadrant pain, fever, and vomiting.

Images of Chlamydial Reactive Arthritis


  • Nucleic acid–based tests of cervical, urethral, pharyngeal, or rectal exudate or urine

Chlamydial, mycoplasmal, or ureaplasmal infection is suspected in patients with symptoms of urethritis, salpingitis, cervicitis, or unexplained proctitis, but similar symptoms can also result from gonococcal infection.

If clinical evidence for urethritis is uncertain, the Centers for Disease Control and Prevention (CDC) 2015 Sexually Transmitted Diseases Treatment Guidelines state that urethritis can be documented by any of the following:

  • Mucoid, mucopurulent, or purulent discharge observed during examination

  • ≥ 10 white blood cells per high-power field in spun first-void urine

  • A positive leukocyte esterase test on first-void urine

  • ≥ 2 white blood cells per oil immersion field in Gram-stained urethral secretions

Samples of cervical or vaginal specimens or male urethral or rectal exudates are obtained to check for chlamydiae. Urine samples can be used as an alternative to cervical or urethral specimens. Throat and rectal swabs are needed to test for infection at those sites.

Commercially available nucleic acid amplification tests (NAATs) are highly sensitive and specific and can also be done on self-collected urine or vaginal specimens, eliminating the need for doing an uncomfortable swab of the urethra or cervix. Point-of-care NAAT platforms are available and can provide same-visit results. In general, samples from the throat and rectum should be tested only in laboratories that have verified the use of these tests for those anatomic sites.

Because other STIs (particularly gonococcal infection) often coexist, patients who have symptomatic urethritis should also be tested for gonorrhea. All patients who receive a diagnosis of gonorrhea or chlamydia should be tested for other STIs, including syphilis and HIV.

Detection of mycoplasmas and Ureaplasma sp is currently impractical in routine practice; some commercial NAAT assays are being developed for mycoplasma but may not be widely available.

In the US, confirmed cases of chlamydial infection, gonorrhea, and syphilis must be reported to the public health system.


Testing urine or self-collected vaginal swabs using NAAT is especially useful for screening asymptomatic people at high risk of STIs because genital examination is not necessary. Screening recommendations vary by sex, age, sexual practices, and setting.

Nonpregnant women (including women who have sex with women) are screened annually if they

  • Are sexually active and < 25 years

  • Have a history of a prior STI

  • Engage in high-risk sexual behavior (eg, have a new sex partner or multiple sex partners, engage in sex work, use condoms inconsistently)

  • Have a partner who engages in high-risk behavior

Pregnant women are screened during their initial prenatal visit; those < 25 years or with risk factors are screened again during the 3rd trimester.

Heterosexually active men are not routinely screened except for those in situations with a high prevalence of chlamydial infection, including those with multiple sex partners, patients at adolescent or STI clinics, and men entering correctional facilities.

Men who have sex with men are screened at least annually if they have been sexually active within the previous year (for insertive intercourse, urine screen; for receptive intercourse, rectal swab; and for oral intercourse, pharyngeal swab). Those with HIV infection, those with multiple sex partners, or those whose partner has multiple partners should be screened more frequently, at 3 to 6-month intervals.

(See also the US Preventive Services Task Force’s summary of recommendations regarding screening for chlamydial infection.)


  • Oral antibiotics (preferably azithromycin)

  • Empiric treatment for gonorrhea if it has not been excluded

  • Treatment of sex partners

Uncomplicated documented or suspected chlamydial, ureaplasmal, or mycoplasmal infections are treated with one of the following:

  • A single dose of azithromycin 1 g orally

  • Doxycycline 100 mg orally twice a day for 7 days

  • Erythromycin as the base 500 mg orally or as ethylsuccinate 800 mg four times a day for 7 days

  • Ofloxacin 300 mg orally twice a day for 7 days

  • Levofloxacin 500 mg orally once a day for 7 days

Azithromycin (given as a single dose) is preferred to drugs that require multiple doses over 7 days, although there is some evidence that doxycycline may be preferable for rectal chlamydia (1 Treatment reference Sexually transmitted urethritis, cervicitis, proctitis, and pharyngitis not due to gonorrhea are caused predominantly by chlamydiae and infrequently by mycoplasmas or Ureaplasma sp. Chlamydiae... read more Treatment reference ).

For pregnant women, azithromycin 1 g orally once should be used.

These regimens do not reliably treat gonorrhea, which coexists in many patients with chlamydial infections. Therefore, treatment should include a single dose of ceftriaxone 250 mg IM if gonorrhea has not been excluded.

Patients who relapse (about 10%) are usually coinfected with microbes that do not respond to antichlamydial therapy, or they were reinfected since treatment.

They should be retested for chlamydial infection and gonorrhea and, if possible, for trichomoniasis. They should be treated with azithromycin unless they were treated with it before. If azithromycin has been ineffective, moxifloxacin (active against azithromycin-resistant Mycoplasma or Ureaplasma species) should be tried. In areas where trichomoniasis is prevalent, empiric treatment with metronidazole is recommended unless polymerase chain reaction (PCR) testing indicates patients are negative for trichomoniasis.

Current sex partners should be treated. Patients should abstain from sexual intercourse until they and their partners have been treated for ≥ 1 week.

If chlamydial genital infections are untreated, symptoms and signs subside within 4 weeks in about two thirds of patients. However, in women, asymptomatic cervical infection may persist, resulting in chronic endometritis, salpingitis, or pelvic peritonitis and their sequelae—pelvic pain, infertility, and increased risk of ectopic pregnancy. Because chlamydial infections can have serious long-term consequences for women, even when symptoms are mild or absent, detecting the infection in women and treating them and their sex partners is crucial.

Treatment reference

  • 1. Kong FYS, Tabrizi SN, Fairley CK, et al: The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J Antimicrob Chemother 70: 1290–1297, 2015. doi: 10.1093/jac/dku574

Key Points

  • Sexually acquired chlamydial, mycoplasmal, and ureaplasmal infections may affect the urethra, cervix, adnexa, throat, or rectum.

  • Diagnose using nucleic acid amplification tests.

  • Also test for coinfection with other STIs, including gonorrhea, syphilis, and HIV infection.

  • Screen high-risk, asymptomatic patients for chlamydial infection.

  • Use an antibiotic regimen that also treats gonorrhea if it has not been excluded.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

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