2.2 Sexually Transmitted Infections: Chlamydia, Gonorrhea, Syphilis & Pelvic Inflammatory Disease
Key Takeaways
Chlamydia trachomatis first-line therapy is oral doxycycline 100 mg twice daily for 7 days; azithromycin 1 g single dose is strictly reserved for pregnant patients or severe adherence barriers.
Neisseria gonorrhoeae is treated with ceftriaxone 500 mg intramuscular monotherapy for patients weighing under 150 kg (1 g for ≥150 kg), adding doxycycline only if chlamydial infection has not been ruled out.
Primary, secondary, and early latent syphilis are treated with benzathine penicillin G 2.4 million units IM single dose, whereas late latent syphilis requires weekly doses for 3 consecutive weeks.
Penicillin is the only proven curative agent for syphilis during pregnancy; pregnant women with documented severe penicillin allergy must undergo hospital desensitization followed by benzathine penicillin G.
Pelvic inflammatory disease requires immediate empiric treatment upon identifying at least one minimum bimanual sign (uterine, adnexal, or cervical motion tenderness) using ceftriaxone 500 mg IM plus oral doxycycline and metronidazole for 14 days.
Sexually Transmitted Infections: Chlamydia, Gonorrhea, Syphilis & PID
Sexually transmitted infections (STIs) and pelvic inflammatory disease (PID) represent crucial priorities in ambulatory women's health. Prompt detection and guideline-adherent pharmacotherapy prevent long-term reproductive complications, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Current Centers for Disease Control and Prevention (CDC) guidelines reflect critical therapeutic updates designed to combat antimicrobial resistance and optimize cure rates.
Important
The CDC STI guidelines recommend oral doxycycline (100 mg twice daily for 7 days) as first-line therapy for uncomplicated urogenital Chlamydia trachomatis, replacing single-dose azithromycin. For uncomplicated Neisseria gonorrhoeae, ceftriaxone 500 mg intramuscular monotherapy is standard for patients weighing under 150 kg.
Chlamydia trachomatis
Chlamydia trachomatis is the most frequently reported bacterial STI in the United States. Infection is predominantly asymptomatic (up to 70–80% of women), serving as a silent reservoir for upper genital tract disease.
Screening & Diagnostics
- Screening: Annual screening is recommended for all sexually active women under 25 years. Women aged 25 and older require annual screening if high-risk factors exist (new or multiple partners, concurrent STI, inconsistent barrier use). Universal screening is mandated at the first prenatal visit, with third-trimester retesting for high-risk patients.
- Diagnostics: Nucleic Acid Amplification Testing (NAAT) from a vaginal swab (patient- or clinician-collected) is the gold standard. First-catch urine and endocervical swabs are acceptable alternatives.
Treatment & Surveillance
- First-Line Regimen: Oral doxycycline 100 mg twice daily for 7 days.
- Alternative / Pregnancy: Oral azithromycin 1 g single dose is reserved for pregnancy (doxycycline is contraindicated) or documented severe non-adherence.
- Surveillance: All patients require rescreening at 3 months post-treatment due to high reinfection rates. A test-of-cure (TOC) via NAAT at 4 weeks is indicated only during pregnancy or when using alternative regimens.
Neisseria gonorrhoeae
Neisseria gonorrhoeae is a fastidious Gram-negative diplococcus infecting mucosal columnar and transitional epithelium, presenting as purulent cervicitis, urethritis, or proctitis.
Diagnostics & Pharmacotherapy
Diagnosis relies on NAAT. Routine dual therapy with azithromycin has been discontinued to avoid promoting macrolide resistance.
- Weight < 150 kg: Ceftriaxone 500 mg intramuscular (IM) in a single dose.
- Weight >= 150 kg: Ceftriaxone 1,000 mg (1 g) IM in a single dose.
- Chlamydia Co-Infection: If chlamydia has not been excluded by NAAT, add oral doxycycline 100 mg twice daily for 7 days (or azithromycin 1 g if pregnant).
- Follow-Up: Uncomplicated gonorrhea treated with ceftriaxone does not require a test-of-cure; repeat screening is recommended at 3 months.
Syphilis (Treponema pallidum)
Syphilis is a systemic venereal infection caused by the spirochete Treponema pallidum. Untreated disease progresses through distinct clinical stages.
| Stage | Clinical Features | Diagnostic Findings |
|---|---|---|
| Primary | Solitary, indurated, painless ulcer (chancre); painless adenopathy | Darkfield microscopy; reactive serology (may lag) |
| Secondary | Non-pruritic maculopapular rash on palms/soles; condylomata lata | Peak non-treponemal titers (RPR >= 1:32); reactive treponemal test |
| Latent | Asymptomatic seropositivity (Early: <1 yr; Late: >1 yr or unknown duration) | Reactive serology without active lesions; normal CSF |
| Tertiary | Gummatous necrosis, aortic aneurysm, aortitis, late neurosyphilis | Reactive treponemal serology; variable non-treponemal titers |
Diagnostic Algorithms
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Traditional Algorithm: Initial non-treponemal screening (RPR or VDRL) detecting anticardiolipin antibodies. Quantitative titers monitor disease activity and therapeutic response (a fourfold decrease indicates cure). Reactive screens require confirmation with a specific treponemal assay (TP-PA or FTA-ABS). Biological false positives occur with pregnancy, lupus, and viral infections.
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Reverse Sequence Algorithm: Automated treponemal immunoassay (EIA/CIA) performed first. If reactive, reflex to quantitative RPR. Discordant results are arbitrated by a second treponemal assay (TP-PA).
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Screening in Pregnancy: CDC recommends syphilis serology for every pregnant patient at the first prenatal visit. Because congenital syphilis rose sharply, ACOG (2024) now recommends universal rescreening in the third trimester (ideally around 28 weeks) and again at delivery.
Pharmacotherapy & Reactions
- Primary, Secondary, Early Latent: Benzathine penicillin G 2.4 million units IM in a single dose.
- Late Latent / Unknown Duration: Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units). Missed doses exceeding 14 days in non-pregnant patients (>7–9 days in pregnancy) require restarting the series.
- Pregnancy & Allergy: Penicillin is the only effective agent during pregnancy. Allergic pregnant patients must undergo desensitization and receive benzathine penicillin G.
- Jarisch-Herxheimer Reaction: An acute systemic febrile reaction (fever, chills, headache) occurring 2–24 hours following spirochetal lysis. It is managed with antipyretics. In pregnancy, it may precipitate uterine contractions or fetal heart rate decelerations.
Pelvic Inflammatory Disease (PID)
Pelvic inflammatory disease is an ascending, polymicrobial infection extending from the endocervix to the endometrium, fallopian tubes, and pelvic peritoneum, involving C. trachomatis, N. gonorrhoeae, Mycoplasma genitalium, and anaerobes.
Clinical Diagnostic Criteria
To prevent irreversible tubal scarring, clinicians must initiate empiric therapy in sexually active women with lower abdominal/pelvic pain who exhibit at least one minimum clinical criterion on bimanual exam:
- Cervical motion tenderness ("chandelier sign")
- Uterine tenderness
- Adnexal tenderness
Supportive criteria include oral temperature >38.3 deg C (101 deg F), abnormal cervical mucopurulent discharge or friability, abundant WBCs on wet mount, elevated ESR or C-reactive protein, and positive gonococcal or chlamydial laboratory results.
Pharmacotherapy & Sequelae
- Outpatient Regimen: Ceftriaxone 500 mg IM single dose (<150 kg) PLUS oral doxycycline 100 mg twice daily for 14 days PLUS oral metronidazole 500 mg twice daily for 14 days. Metronidazole ensures coverage against anaerobes and bacterial vaginosis.
- Inpatient Criteria: Pregnancy, surgical emergencies unexcluded (appendicitis), severe illness/vomiting, tubo-ovarian abscess (TOA), or failure of outpatient therapy after 48–72 hours. Inpatient regimens include IV cefotetan or cefoxitin plus doxycycline.
- Long-Term Sequelae: Tubal factor infertility (~8% after 1 episode, ~20% after 2, ~40% after 3), 7- to 10-fold increased ectopic pregnancy risk, and chronic pelvic pain.
A 22-year-old female presents to the clinic after learning that her sexual partner was treated for gonorrhea. A point-of-care urine pregnancy test is negative. Endocervical NAAT testing confirms Neisseria gonorrhoeae infection and is negative for Chlamydia trachomatis. The patient weighs 62 kg and has no drug allergies. According to current CDC guidelines, what is the most appropriate treatment?
Ceftriaxone 250 mg IM single dose plus azithromycin 1 g orally single dose
Ciprofloxacin 500 mg orally in a single dose
Ceftriaxone 500 mg IM in a single dose
Doxycycline 100 mg orally twice daily for 7 days
A 27-year-old female at 14 weeks of gestation presents for prenatal care. She reports a generalized, non-pruritic maculopapular rash involving her trunk, palms, and soles for the past 2 weeks. Speculum examination reveals moist, flat, vegetative lesions on the labia majora. Serum RPR is reactive at a titer of 1:64, and TP-PA testing is reactive. The patient has a documented history of severe penicillin anaphylaxis with hives and bronchospasm. What is the most appropriate management?
Oral doxycycline 100 mg twice daily for 14 days
Penicillin desensitization, then benzathine penicillin G
Oral azithromycin 2 g as a single dose under observation
Intramuscular ceftriaxone 1 g daily for 10 to 14 days
A 19-year-old sexually active female presents with a 3-day history of bilateral lower abdominal pain and dyspareunia. Vital signs reveal a temperature of 38.4°C (101.1°F), heart rate 88 bpm, and blood pressure 114/72 mmHg. Bimanual pelvic examination elicits marked cervical motion tenderness and right adnexal tenderness without a palpable adnexal mass. Saline wet mount reveals numerous white blood cells and absence of trichomonads. Urine pregnancy test is negative. She is tolerating fluids without nausea. What is the most appropriate next step in clinical management?
Start ceftriaxone 500 mg IM once plus oral doxycycline 100 mg and metronidazole 500 mg twice daily for 14 days
Order an urgent outpatient pelvic ultrasound and withhold antibiotic therapy until pelvic ultrasound results confirm salpingitis
Prescribe oral azithromycin 1 g as a single dose and advise follow-up in 2 weeks if pain persists
Admit the patient for immediate diagnostic laparoscopy before starting any antibiotic therapy
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