Sexually Transmitted Infections: The USMLE Step 1 Guide
Sexually transmitted infections share a route but differ in what they do to the body: discharge, ulcers, warts, or systemic disease years later. Step 1 tests the organism behind each presentation, the diagnostic clue (painful or painless ulcer, clue cells, motile trichomonads), and the drug. Syphilis gets its own timeline because its stages are a favorite question.
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update Updated October 2026
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Written for USMLE Step 1 · Free to read
bolt The 60-second version
Sexually transmitted infections share a route but differ in what they do to the body: discharge, ulcers, warts, or systemic disease years later. Step 1 tests the organism behind each presentation, the diagnostic clue (painful or painless ulcer, clue cells, motile trichomonads), and the drug.
check_circleChlamydia trachomatis is the most common bacterial STI in the US; it is an obligate intracellular organism with elementary and reticulate bodies.
check_circleNeisseria gonorrhoeae: gram-negative diplococci in neutrophils; treat with ceftriaxone and add doxycycline if chlamydia is not excluded.
check_circlePainless ulcer = syphilis (chancre) or lymphogranuloma venereum; painful ulcer = HSV or chancroid (Haemophilus ducreyi).
check_circleSyphilis stages: primary chancre, secondary rash on palms and soles with condylomata lata, latent, and tertiary gummas, aortitis, and tabes dorsalis.
check_circlePenicillin G is the treatment of choice for syphilis; a Jarisch-Herxheimer reaction may follow the first dose.
target What you'll be able to do · aligned to USMLE Step 1 · Microbiology & Reproductive System
MICROIdentify the organisms that cause urethritis, cervicitis, genital ulcers, and vaginitis.
MICRODescribe the stages of syphilis and interpret treponemal and nontreponemal tests.
MICRODistinguish trichomoniasis, bacterial vaginosis, and candidiasis by discharge, pH, and microscopy.
PHARMChoose first-line therapy for chlamydia, gonorrhea, syphilis, and trichomoniasis.
How STIs are tested on Step 1
Questions start from a syndrome — urethritis, cervicitis, vaginitis, genital ulcer, arthritis, or neonatal conjunctivitis — and ask for the organism, the lab finding, or the treatment.
workspace_premium Test for one, think of all
STIs travel together. A diagnosis of one should prompt testing for HIV, syphilis, chlamydia, and gonorrhea, and treatment of partners.
Chlamydia and gonorrhea
Both cause urethritis, cervicitis, pelvic inflammatory disease, and neonatal conjunctivitis. Nucleic acid amplification testing of urine or a swab detects both.
Chlamydia vs gonorrhea. Both can cause PID, ectopic pregnancy, infertility, and Fitz-Hugh–Curtis perihepatitis ("violin-string" adhesions).
Genital ulcers
Pain is the first branch point.
Disease
Organism
Ulcer
Lymph nodes
Diagnosis
Primary syphilis
Treponema pallidum
Painless, indurated, clean base
Painless, rubbery
Dark-field microscopy; VDRL/RPR and treponemal tests
Genital herpes
HSV-2 (or HSV-1)
Painful grouped vesicles that ulcerate
Tender
PCR; Tzanck shows giant cells
Chancroid
Haemophilus ducreyi
Painful, ragged, purulent base
Tender, may suppurate
"School of fish" on Gram stain
Lymphogranuloma venereum
C. trachomatis L1–L3
Small painless ulcer, often unnoticed
Painful buboes, may form fistulas
NAAT; serology
Granuloma inguinale
Klebsiella granulomatis
Painless, beefy red, bleeds easily
Usually none
Donovan bodies
Mnemonic: "You do cry with ducreyi" — chancroid hurts; syphilis does not.
Syphilis stages
Untreated syphilis progresses over years. Nontreponemal tests (VDRL, RPR) track activity; treponemal tests (FTA-ABS) stay positive for life.
Syphilis stages. Tertiary disease includes aortitis (tree-bark aorta, ascending aneurysm), neurosyphilis (tabes dorsalis, Argyll Robertson pupil, general paresis), and gummas.
Test
Type
Use
VDRL, RPR
Nontreponemal (anticardiolipin)
Screening and monitoring response; false positives in SLE, pregnancy, viral infection
Three causes of vaginal discharge are tested side by side.
Vaginitis. Metronidazole treats trichomoniasis (treat partners) and bacterial vaginosis (Gardnerella overgrowth, not strictly an STI); azoles treat candidiasis.
functions Worked example — the ulcer that doesn't hurt
A 26-year-old has a firm, painless ulcer on the penis with clean edges and painless inguinal lymphadenopathy. RPR is positive. What is the treatment, and what may happen within hours of the first dose?
A painless, indurated ulcer with a positive RPR is primary syphilis.
Benzathine penicillin G, a single intramuscular dose, treats early syphilis.
Rapid killing of spirochetes releases lipoproteins that trigger cytokines.
Answer. Benzathine penicillin G IM. Fever, chills, and myalgias within 24 hours represent the Jarisch-Herxheimer reaction, which is managed supportively.
1. A sexually active man develops conjunctivitis, urethritis, and asymmetric knee arthritis 3 weeks after an episode of urethral discharge. Which organism most likely triggered this?
Explanation. Reactive arthritis classically follows chlamydial urethritis (or enteric infections) and is associated with HLA-B27.
2. A patient has a rash on the palms and soles and moist, flat, gray-white lesions in the perianal area. What are these lesions?
Explanation. Condylomata lata are highly infectious lesions of secondary syphilis; condylomata acuminata are HPV warts.
3. Wet mount of a frothy, malodorous vaginal discharge shows motile pear-shaped organisms with flagella. What is the treatment?
Explanation. Trichomonas vaginalis is treated with metronidazole; partners must be treated to prevent reinfection.
Frequently asked questions
Which genital ulcers are painful?expand_more
Herpes simplex (grouped vesicles that ulcerate) and chancroid from Haemophilus ducreyi. Syphilis, lymphogranuloma venereum, and granuloma inguinale are usually painless.
What are the stages of syphilis?expand_more
Primary (painless chancre), secondary (rash on palms and soles, condylomata lata, lymphadenopathy), latent (no symptoms, positive serology), and tertiary (gummas, aortitis, neurosyphilis).
How are gonorrhea and chlamydia treated?expand_more
Gonorrhea is treated with intramuscular ceftriaxone. Chlamydia is treated with doxycycline, or azithromycin in pregnancy. If chlamydia has not been excluded in a patient treated for gonorrhea, doxycycline is added.
What are clue cells?expand_more
Vaginal epithelial cells coated with Gardnerella vaginalis and other anaerobes, giving them a stippled border. They indicate bacterial vaginosis.
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