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.
Try two board-style Chlamydia trachomatis Genital Infection questions
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Question 1ReproductiveMedium
A 22-year-old woman presents with 5 days of yellow vaginal discharge and mild dysuria. She has a new sexual partner and inconsistent condom use. She denies abdominal pain, fever, or abnormal bleeding. Temperature 37.0 C, BP 118/74 mm Hg. Pelvic exam shows mucopurulent cervical discharge without cervical motion tenderness. Nucleic acid amplification testing of a vaginal swab is positive for Chlamydia trachomatis and negative for Neisseria gonorrhoeae. Urine pregnancy test is negative. Which of the following is the recommended first-line treatment?
AMetronidazole 500 mg orally twice daily for 7 days
BDoxycycline 100 mg orally twice daily for 7 days
CCeftriaxone 500 mg intramuscularly once
DAmoxicillin 500 mg orally 3 times daily for 7 days
EAzithromycin 1 g orally once
Reveal answer & full explanation
Correct answer: B — Doxycycline 100 mg orally twice daily for 7 days
AMetronidazole 500 mg orally twice daily for 7 days
BDoxycycline 100 mg orally twice daily for 7 days✓
CCeftriaxone 500 mg intramuscularly once
DAmoxicillin 500 mg orally 3 times daily for 7 days
EAzithromycin 1 g orally once
Why Doxycycline 100 mg orally twice daily for 7 days is correct
Doxycycline 100 mg orally twice daily for 7 days is the current CDC first-line treatment for uncomplicated urogenital Chlamydia trachomatis infection in nonpregnant adults (2021 STI Treatment Guidelines)
Microbiologic cure rates with doxycycline are superior to single-dose azithromycin (approximately 97% vs 94%)
Azithromycin failures are substantially higher for rectal chlamydia specifically
Why the others are wrong
Azithromycin 1 g orally once — previously co-first-line and still acceptable when adherence is a concern or in pregnancy, but no longer the preferred regimen because of inferior efficacy
Ceftriaxone 500 mg intramuscularly once — first-line for gonorrhea, not chlamydia; would be added if NAAT were positive for N. gonorrhoeae or empirically when gonorrhea cannot be excluded
Metronidazole 500 mg orally twice daily for 7 days — covers trichomoniasis and bacterial vaginosis, not chlamydia
Amoxicillin 500 mg orally 3 times daily for 7 days — an alternative regimen for chlamydia in pregnancy, which tempts students treating a woman of reproductive age, but her pregnancy test is negative and amoxicillin is not a recommended regimen for nonpregnant adults, in whom doxycycline is preferred
Additional high-yield points
Sexual partners within the past 60 days should be evaluated and treated
The patient should abstain from intercourse for 7 days after starting therapy
Test of reinfection (not test of cure) is recommended at 3 months
Question 2Infectious DiseaseMedium
A 32-year-old man develops fever, night sweats, and tender bilateral inguinal lymphadenopathy three weeks after unprotected intercourse. He recalls a small, painless penile ulcer that has since healed. Nucleic acid amplification testing of an inguinal lymph node aspirate is positive for Chlamydia trachomatis. Which of the following is the most likely diagnosis?
ALymphogranuloma venereum
BGranuloma inguinale
CChancroid
DPrimary syphilis
EPrimary genital herpes
Reveal answer & full explanation
Correct answer: A — Lymphogranuloma venereum
ALymphogranuloma venereum✓
BGranuloma inguinale
CChancroid
DPrimary syphilis
EPrimary genital herpes
Why Lymphogranuloma venereum is correct
Caused by the invasive Chlamydia trachomatis serovars L1-L3; a positive C. trachomatis NAAT from a lymph node aspirate plus a compatible syndrome is enough to diagnose and treat, because serovar genotyping is not widely available
Classic course: a small painless primary ulcer (often already healed) followed by painful, tender inguinal lymphadenopathy (buboes)
The 'groove sign' occurs when adenopathy forms both above and below the inguinal ligament
Why the others are wrong
Chancroid — Haemophilus ducreyi causes a painful (not painless) genital ulcer with tender adenopathy, but the node aspirate would not be positive for C. trachomatis (premature closure on 'painful ulcer with nodes')
Granuloma inguinale — Klebsiella granulomatis causes progressive beefy-red ulcerative lesions without true buboes (buzzword-matching on tropical STI)
Primary syphilis — Treponema pallidum produces a painless chancre with nontender, rubbery regional nodes rather than tender buboes, and would not yield a C. trachomatis-positive node aspirate (anchoring on 'painless ulcer = syphilis')
Primary genital herpes — primary herpes simplex infection does cause fever, malaise, and tender bilateral inguinal lymphadenopathy, but its lesions are multiple painful vesicles that erode into shallow ulcers, the adenopathy accompanies the active lesions rather than following a healed painless ulcer by weeks, and the node aspirate would not be positive for C. trachomatis (anchoring on 'fever with tender bilateral nodes')
Additional high-yield points
Rectal LGV (common in men who have sex with men): proctitis, rectal pain, bloody discharge
Treatment: doxycycline 100 mg twice daily for 21 days; test and treat partners
Fluctuant buboes may be aspirated through intact skin or incised and drained to prevent inguinal or femoral ulceration (CDC 2021)
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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
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
UTI — Abrupt dysuria and frequency, often hematuria; nitrite or urine culture positive. Dysuria with pyuria but a sterile culture (sterile pyuria) in a young sexually active woman suggests chlamydial or gonococcal urethritis, so send NAAT
Diagnostic workup
Diagnostic criteria
Positive NAAT in symptomatic or screened asymptomatic patient.
Labs
Nucleic acid amplification test (NAAT) — gold standard; sensitivity >95%
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 — treat both presumptively for cervicitis in women at increased risk (age <25, new partner, partner with an STI) or when follow-up is uncertain or NAAT is unavailable, and for urethritis when a point-of-care Gram stain is unavailable; if the chlamydia NAAT is positive and the gonorrhea NAAT negative, doxycycline alone is enough; PID adds metronidazole and extends therapy to 14 days
Second-line / adjunct
Levofloxacin 500 mg PO daily × 7 days — alternative regimen (as is azithromycin 1 g PO × 1)
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
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.