Infectious Disease · PANCE / PANRE

Chlamydia trachomatis Genital Infection

Most common bacterial STI in the US — often asymptomatic; serotypes D-K cause urogenital infection. Cervicitis/urethritis treated with doxycycline.

Also known as: chlamydia, Chlamydia trachomatis, urethritis, cervicitis, PID

Overview

Infection of genitourinary epithelium by Chlamydia trachomatis, an obligate intracellular gram-negative bacterium. Serovars D-K cause urogenital infection; A-C cause trachoma (ocular); L1-L3 cause lymphogranuloma venereum. Vertical transmission causes neonatal conjunctivitis and pneumonia.

Epidemiology

Most commonly reported notifiable infection in the US — 1.6 million cases in 2022 (CDC), with true incidence likely much higher due to asymptomatic infection. Peaks in ages 15-24; women disproportionately affected. Frequently coinfects with gonorrhea.

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Risk factors

Age <25, multiple sexual partners
New partner within 60 days, inconsistent condom use
Prior STI history
Sex work, MSM (rectal/pharyngeal infection)
Mother with untreated chlamydia (neonatal infection)

Pathophysiology

Elementary bodies (infectious form) attach to and invade columnar epithelial cells of cervix, urethra, rectum, conjunctiva. Inside, they convert to reticulate bodies and replicate within inclusions, then revert to elementary bodies and are released. Persistent infection drives chronic inflammation that scars the upper genital tract — causing tubal infertility and chronic pelvic pain.

Clinical presentation

Symptoms

Women (often asymptomatic): mucopurulent cervical discharge, intermenstrual or post-coital bleeding, dysuria
Men: urethral discharge (clearer/whiter than gonorrhea), dysuria, urethral itching; ~50% asymptomatic
Rectal infection: often asymptomatic; proctitis with pain, discharge, tenesmus possible
Pharyngeal: usually asymptomatic
Neonatal: conjunctivitis (5-14 days), staccato-cough pneumonia (3-12 weeks)
Reiter syndrome (reactive arthritis): urethritis + conjunctivitis + asymmetric oligoarthritis

Signs / physical exam

Mucopurulent cervical discharge; friable cervix; cervical motion tenderness
Urethral meatus erythema, discharge expressible
Lower abdominal tenderness if ascending infection
Conjunctival injection with mucopurulent discharge (neonate or adult inclusion conjunctivitis)

Classic findings

Sexually active young woman with intermenstrual or post-coital bleeding and mucopurulent cervicitis — chlamydia until proven otherwise. Test all sexually active women under 25 annually.

Differential diagnosis

Gonorrhea — More purulent discharge, concurrent in ~30%; treat for both empirically
Mycoplasma genitalium — Persistent urethritis/cervicitis after standard therapy; NAAT; macrolide resistance common
Trichomoniasis — Frothy, malodorous vaginal discharge, strawberry cervix; NAAT or wet mount
Bacterial vaginosis — Thin gray discharge, fishy odor, clue cells, pH >4.5
HSV cervicitis — Painful vesicles/ulcers, dysuria; PCR
Pelvic inflammatory disease — Adnexal/cervical motion tenderness, fever; treat broadly
UTI — Dysuria with pyuria but negative for STI; urine culture

Diagnostic workup

Diagnostic criteria

Positive NAAT in symptomatic or screened asymptomatic patient.

Labs

Nucleic acid amplification test (NAAT) — gold standard; sensitivity >95%
Specimens: first-catch urine (men/women), endocervical swab, vaginal swab (provider or patient self-collected), urethral swab, rectal swab, pharyngeal swab
Co-test for gonorrhea at the same time and site (frequent coinfection)
Screen for syphilis and HIV; offer hepatitis screening as indicated
Wet mount for trichomoniasis if discharge
USPSTF recommends annual chlamydia screening for sexually active women <25 and older women with risk factors

Imaging

Pelvic ultrasound if PID with tubo-ovarian abscess suspected
Generally none required for uncomplicated infection

Diagnostic algorithm

Population/Site	First-line Therapy	Notes
Urogenital (non-pregnant)	Doxycycline 100 mg BID x 7 d	Preferred over azithromycin
Pregnancy	Azithromycin 1 g PO x 1	Doxycycline contraindicated; test of cure at 4 wk
Rectal	Doxycycline 100 mg BID x 7 d	Azithromycin inferior here
LGV (L1-L3)	Doxycycline 100 mg BID x 21 d	Inguinal/anal bubo; MSM
Neonatal	Erythromycin x 14 d (PO)	Counsel for pyloric stenosis risk

CDC 2021 chlamydia treatment by site and host.

Treatment

First-line

Uncomplicated urogenital chlamydia (CDC 2021):
• Doxycycline 100 mg PO BID × 7 days — preferred (more effective than azithromycin for rectal and pharyngeal infections)
• Azithromycin 1 g PO × 1 — alternative if adherence concerns or pregnancy (single dose, observed therapy)
Rectal chlamydia: doxycycline 100 mg PO BID × 7 days (azithromycin inferior)
LGV (L1-L3 serovars): doxycycline 100 mg PO BID × 21 days
Pregnancy: azithromycin 1 g PO × 1 (doxycycline contraindicated)
Neonatal conjunctivitis or pneumonia: erythromycin base or ethylsuccinate PO × 14 days (parents counseled about pyloric stenosis risk)
Ceftriaxone for gonorrhea + doxycycline for chlamydia — empiric treatment of concurrent gonorrhea is no longer routine without positive gonorrhea NAAT, but combination remains the empiric regimen when both organisms are likely (e.g., PID)

Second-line / adjunct

Levofloxacin 500 mg PO daily × 7 days — second-line, particularly for epididymitis
Expedited partner therapy (EPT) — provide medication or prescription to give to partners (legal in most states)
Test of cure NOT routinely recommended (except pregnancy at 4 weeks post-treatment)
Rescreen at 3 months for reinfection regardless of partner treatment

Complications

Pelvic inflammatory disease (PID) → tubal infertility, ectopic pregnancy, chronic pelvic pain
Fitz-Hugh-Curtis syndrome (perihepatitis with 'violin string' adhesions and RUQ pain)
Epididymitis, prostatitis (men)
Reactive arthritis (Reiter syndrome)
Neonatal conjunctivitis (1-2 weeks), pneumonia (3-12 weeks)
Increased HIV transmission risk

PANCE pearls

Doxycycline is now preferred over single-dose azithromycin for urogenital chlamydia (CDC 2021) — particularly important for rectal infections.
Routine annual NAAT screening for all sexually active women <25 (USPSTF Grade B).
Treat partners and counsel for 7 days of abstinence after treatment to prevent reinfection.
Persistent symptoms after appropriate therapy — consider Mycoplasma genitalium (NAAT) or reinfection.
Pregnancy: azithromycin replaces doxycycline; test of cure at 4 weeks post-treatment.

References

CDC 2021 — Sexually Transmitted Infections Treatment Guidelines, 2021 (MMWR Recommendations and Reports)
USPSTF 2021 — Screening for Chlamydia and Gonorrhea: US Preventive Services Task Force Recommendation Statement
CDC Surveillance — Sexually Transmitted Disease Surveillance — Chlamydia chapter

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