SexuallyTransmitted Infections: Overview and Clinical Approach¶
Chapter 141 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 141
Key Clinical Points¶
- Ceftriaxone 500 mg IM is the preferred treatment for gonorrhea; oral cephalosporins and fluoroquinolones are contraindicated due to resistance.
- Mycoplasma genitalium is a probable cause of Chlamydia-negative urethritis and requires moxifloxacin or azithromycin.
- All adults should be screened for HIV-1 at least once; routine screening for Chlamydia is recommended for sexually active females ≤25 years.
- Bacterial Vaginosis (BV) is associated with increased risk of HIV transmission and adverse pregnancy outcomes (preterm labor).
- Gram stain of urethral exudate showing ≥2 neutrophils per 1000× field confirms urethritis; gram-negative intracellular diplococci indicate gonorrhea.
- Syphilis incidence in the US peaked in 2022 with 207,255 cases reported, the highest since 1950, driven by MSM networks.
- Doxycycline is the preferred antibiotic for Chlamydia trachomatis; azithromycin is an alternative but resistance to M. genitalium is emerging.
- Epididymitis in men <35 is usually C. trachomatis; in older men or post-instrumentation, it is usually Enterobacteriaceae.
- Vulvovaginal candidiasis presents with clumped, adherent plaques; Trichomoniasis presents with homogeneous, low viscosity discharge.
- PrEP for HIV is associated with reduced condom use and increased STI acquisition among MSM.
DEFINITION & CLASSIFICATION¶
• Overview: STIs are infections acquired primarily through sexual contact. • Global Impact: Over 1 million STIs acquired daily; many lead to complications. • Transmission Dynamics: ◦ High-risk networks (syphilis, gonorrhea, HIV, hepatitis B, chancroid) involve high rates of partner change or multiple concurrent partners. ◦ Low-risk/Broad transmission: Chlamydia, genital HPV, and genital herpes spread even in lower-risk populations. • Microbial Diversity: ◦ Includes bacteria (e.g., N. gonorrhoeae, C. trachomatis), viruses (e.g., HIV, HSV, HPV, HBV), and other organisms (e.g., Trichomonas vaginalis).
Classification of Microorganisms¶
Definition (Harrison's 22e): Bacteria (Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Haemophilus ducreyi, Klebsiella (Calymmatobacterium) granulomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis), Viruses (HIV types 1 and 2, Human T-cell lymphotropic virus type 1, Herpes simplex virus type 2, Human papillomavirus, Hepatitis B virus, Molluscum contagiosum virus, Cytomegalovirus, Epstein-Barr virus, Human herpesvirus type 8, Zika virus), Other (Trichomonas vaginalis, Pthirus pubis, Sarcoptes scabiei, Giardia lamblia, Entamoeba histolytica).
EPIDEMIOLOGY¶
• Global Trends: ◦ Developing countries: High vulnerability due to population growth, rural-to-urban migration, and limited reproductive health services. ◦ Major concerns: HIV (leading cause of death in some areas), HPV/HBV (cancer drivers). ◦ Curable STIs: ~357 million new cases annually; all associated with increased risk of HIV transmission/acquisition. • United States Epidemiology: ◦ HSV-2: Prevalence falling since late 1990s due to delayed sexual debut and condom use. ◦ HBV: Incidence declined significantly since mid-1980s due to infant vaccination. ◦ HPV: Most common STI in the US; high prevalence in young women. ◦ Gonorrhea: Significant resurgence since 2009 (80% increase); higher rates than other Western countries. ◦ Syphilis: Record highs in 2022 (207,255 cases); 45% of male cases among MSM; significant rise in congenital syphilis. ◦ Chlamydia: Steady increase since 1984.
Impact of PrEP¶
• Observation: PrEP for HIV is associated with reduced condom use and increased STI acquisition among MSM.
ETIOLOGY & PATHOPHYSIOLOGY¶
• Transmission Factors: ◦ 1. Rate of sexual exposure (mitigated by education, behavior change, PEP). ◦ 2. Efficiency of transmission per exposure (mitigated by condoms, vaccines, male circumcision). ◦ 3. Duration of infectivity (mitigated by early diagnosis and treatment). • Network Dynamics: ◦ High-risk networks: Syphilis, gonorrhea, HIV, HBV, chancroid. ◦ Broad transmission: Chlamydia, HPV, HSV.
CLINICAL FEATURES¶
• General Approach: Management based on symptoms, signs, and risk factors (age, gender, residence). • Urethritis in Men: ◦ Symptoms: Urethral discharge, dysuria. ◦ Pathogens: N. gonorrhoeae, C. trachomatis, M. genitalium, U. urealyticum, T. vaginalis, HSV. ◦ Trends: C. trachomatis share of NGU declining; M. genitalium is a common cause of Chlamydia-negative cases. ◦ Risk Factors: Older men less likely to have chlamydial infection; coliforms/anaerobes associated with insertive anal intercourse. • Urethral Syndrome in Women: ◦ Symptoms: Internal dysuria, pyuria, absence of E. coli or other uropathogens at ≥10^2/mL. ◦ Differentiation: Distinguish from bacterial UTI (characterized by urgency, frequency, and presence of uropathogens) and vulvovaginitis (external dysuria due to inflammation).
Epididymitis¶
• Presentation: Acute, usually unilateral; pain, swelling, tenderness. ◦ Differentiation: Must rule out testicular torsion (surgical emergency), tumor, or trauma. ◦ Etiology (<35 years): Usually C. trachomatis and N. gonorrhoeae. ◦ Etiology (>35 years/post-instrumentation): Usually Enterobacteriaceae. ◦ Etiology (MSM insertive anal): Often Enterobacteriaceae.
Vulvovaginal Infections¶
• Clinical Assessment: Requires speculum/pelvic exam to distinguish between candidiasis, trichomoniasis, and BV. ◦ Candidiasis: Clumped, adherent plaques; white discharge; itching. ◦ Trichomoniasis: Homogeneous, low viscosity, yellow/white discharge. ◦ Bacterial Vaginosis (BV): Malodorous, gray/white discharge; clue cells on wet mount.
DIFFERENTIAL DIAGNOSIS¶
• Urethritis vs. Surgical Emergencies: ◦ Must differentiate from testicular torsion (sudden pain, elevated testicle, no blood flow on Doppler), tumor, and trauma. • Urethral Syndrome vs. UTI: ◦ Distinguish via risk assessment: Syphilis/Chlamydia suspected in young patients with ≥1 partner or new partners; UTI suggested by presence of E. coli or S. saprophyticus.
DIAGNOSTIC APPROACH¶
- Initial Screening: • Gram stain of urethral exudate → identify ≥2 neutrophils/1000x field (confirms urethritis) and gram-negative intracellular diplococci (indicates gonorrhea).
- Routine Testing: • Perform NAATs for N. gonorrhoeae and C. trachomatis.
- Targeted Testing based on Clinical Presentation: • If Chlamydia-negative urethritis: Test for M. genitalium. • For Trichomoniasis: Use NAAT of a urethral swab or specimen obtained before voiding.
- Syphilis Screening: • Dark-field, direct FA, or PCR (for immediate results) and RPR/VDRL/EIA serology.
MANAGEMENT & TREATMENT¶
- Urethritis in Men: • Gonorrhea: Ceftriaxone 500 mg IM (Note: 1 g for patients ≥ 150 kg). • Chlamydia: Doxycycline 100 mg PO BID for 10 days. • Mycoplasma genitalium: Moxifloxacin or Azithromycin. • Trichomoniasis: Metronidazole (various regimens: 2g single dose or 500mg BID x 7 days).
- Epididymitis: • Treatment follows the same protocol as urethritis based on suspected agent.
- Genital Ulcers: • Syphilis: Benzathine penicillin 2.4 million units IM once (to patient and recent partners). • Herpes: Acyclovir, valacyclovir, or famciclovir. • Chancroid: Ciprofloxacin (500 mg PO single dose) OR Ceftriaxone (250 mg IM single dose) OR Azithromycin (1 g PO single dose).
- Pelvic Inflammatory Disease (PID): • Outpatient: Ceftriaxone 500 mg IM + Doxycycline 100 mg PO BID x 14 days + Metronidazole 500 mg PO BID x 14 days. • Inpatient (Regimen A): Cefotetan or cefoxitin (2g) + Doxycycline (100mg). • Inpatient (Regimen B): Clindamycin (900mg) + Gentamicin (loading 2 mg/kg, then 1.5 mg/kg q8h).
Management of Recurrence¶
• Step 1: Confirm objective evidence of urethritis. • Step 2: If re-exposed to untreated/new partner → repeat treatment for both. • Step 3: If no re-exposure → consider T. vaginalis (metronidazole) or resistant M. genitalium (azithromycin followed by moxifloxacin).
COMPLICATIONS & PROGNOSIS¶
• General: Infertility, PID, ectopic pregnancy, and increased HIV transmission risk. • Pregnancy-specific: ◦ Syphilis: Congenital syphilis, stillbirths, neonatal death. ◦ BV: Increased risk of preterm labor and low birth weight. ◦ Chlamydia/Gonorrhea: Risk of PID → infertility or ectopic pregnancy. • Neoplasias: ◦ HPV (types 16, 18, 31, 45) → Cervical, anal, vulvar, vaginal, or penile cancers. ◦ HHV-8 → Kaposi's sarcoma, body-cavity lymphomas. ◦ HTLV-1 → T-cell leukemia, Tropical spastic paraparesis. ◦ HBV → Hepatocellular carcinoma.
SPECIAL POPULATIONS¶
• MSM: ◦ Higher risk for syphilis and gonorrhea. ◦ Benefit from PrEP but may have higher STI rates due to reduced condom use. ◦ Require regular STI screening while on PrEP.
MSM and PrEP¶
• Risk: Higher incidence of syphilis, gonorrhea, and HIV. • Intervention: PrEP (tenofovir/emtricitabine) is highly effective for HIV but requires concurrent STI screening.
KEY PEARLS & HIGH-YIELD POINTS¶
• Diagnostic Clues: ◦ Gram stain: ≥2 neutrophils/1000x field = urethritis; gram-negative intracellular diplococci = gonorrhea. ◦ BV: Malodorous, low-viscosity discharge + clue cells on wet mount. ◦ Syphilis in MSM: Often presents with chancre or lymphadenopathy. ◦ PrEP Trap: May mask STI symptoms due to reduced condom use; regular screening is mandatory.
Clinical Differentiation of Ulcers¶
• Syphilis: 9–90 day incubation, single painless ulcer, firm base. • Herpes: 2–7 day incubation, multiple painful vesicles/ulcers. • Chancroid: 1–14 day incubation, multiple tender "punched-out" ulcers with undermined edges. • LGV: 3 days–6 weeks incubation, tender lymphadenopathy (inguinal/femoral).
Reference Tables¶
TABLE 141-1 Sexually Transmitted and Sexually Transmissible Microorganisms BACTERIA Transmitted in Adults Predominantly…¶
Harrison's 22e, p.1096
| BACTERIA | VIRUSES | OTHERa |
|---|---|---|
| Transmitted in Adults Predominantly by Sexual Intercourse | ||
| Neisseria gonorrhoeae Chlamydia trachomatis Treponema pallidum Haemophilus ducreyi Klebsiella (Calymmatobacterium) granulomatis Ureaplasma urealyticum Mycoplasma genitalium |
HIV (types 1 and 2) Human T-cell lymphotropic virus type 1 Herpes simplex virus type 2 Human papillomavirus (multiple genital genotypes) Hepatitis B virusb Molluscum contagiosum virus |
Trichomonas vaginalis Pthirus pubis |
| Sexual Transmission Repeatedly Described but Not Well Defined or Not the Predominant Mode |
||
| 141 | Sexually Transmitted Infections: Overview and Clinical Approach Jeanne M. Marrazzo |
|
| Transmitted by Sexual Contact Involving Oral–Fecal Exposure; of Declining Importance in Men Who Have Sex with Men |
||
| Shigella spp. Campylobacter spp. |
Hepatitis A virus | Giardia lamblia Entamoeba histolytica |
TABLE 141-2 Major Sexually Transmitted Disease Syndromes and Sexually Transmitted Microbial Etiologies¶
Harrison's 22e, p.1097
| SYNDROME | SEXUALLY TRANSMITTED MICROBIAL ETIOLOGIES |
|---|---|
| AIDS | HIV types 1 and 2 |
| Epididymitis | C. trachomatis, N. gonorrhoeae, and (in older men or men who have sex with men) coliform bacteria |
| Acute pelvic inflammatory disease |
N. gonorrhoeae, C. trachomatis, BV-associated bacteria, M. genitalium, group B streptococci |
| Ulcerative lesions of the genitalia |
HSV-1, HSV-2, Treponema pallidum, Haemophilus ducreyi, C. trachomatis (LGV strains), Klebsiella (Calymmatobacterium) granulomatis |
| Intestinal infections | |
| Proctitis | C. trachomatis, N. gonorrhoeae, HSV, T. pallidum |
| Proctocolitis or enterocolitis | Campylobacter spp., Shigella spp., Entamoeba histolytica, Helicobacter spp., other enteric pathogens |
| Enteritis | Giardia lamblia |
| Genital and anal warts | HPV (30 genital types) |
| Hepatitis | Hepatitis viruses, T. pallidum, CMV, EBV |
| Tropical spastic paraparesis | HTLV-1 |
| Pubic lice | Pthirus pubis |
TABLE 141-3 Eleven-Question Sexually Transmitted Disease¶
Harrison's 22e, p.1098
| Framing Statement | |
|---|---|
| In order to provide the best care for you today and to understand whether we should consider certain infections, I’d like to talk about your sexual behavior. |
|
| Screening Questions | |
| (1) D o you have any reason to think you might have a sexually transmitted infection? If so, what reason? (2) F or all adolescents <18 years old: Have you begun having any kind of sex yet? |
|
| STD History | |
| (3) H ave you ever had any sexually transmitted infections or any genital infections? If so, which ones? |
|
| Sexual Preference | |
| (4) H ave you had sex with men, women, or both? | |
| Injection Drug Use | |
| (5) H ave you ever injected yourself with drugs? (If yes, have you ever shared needles or injection equipment?) (6) H ave you ever had sex with anyone who had ever injected drugs? |
|
| Characteristics of Partner(s) | |
| (7) H ave any of your sex partners had any sexually transmitted infections? If so, which ones? (8) H ave any of your sex partners had other sex partners during the time you’ve been together? |
|
| STD Symptoms Checklist | |
| (9) H ave you recently developed any of these symptoms? | |
| For Men | For Women |
| (a) Discharge of pus (drip) from the penis (b) Genital sores (ulcers) or rash |
(a) Abnormal vaginal discharge (increased amount, abnormal odor, abnormal yellow color) (b) Genital sores (ulcers), rash, or itching |
| Sexual Practices, Past 2 Months (for patients answering yes to any of the above questions, to guide examination and testing) |
|
| (10) Now I’d like to ask what parts of your body may have been sexually exposed to an STD (e.g., your penis, mouth, vagina, anus). |
|
| Query About Interest in STD Screening Tests (for patients answering no to all of the above questions) |
|
| (11) Would you like to be tested for HIV or any other STDs today? (If yes, clinician can explore which STD and why.) |
TABLE 141-4 Management of Urethral Discharge in Men¶
Harrison's 22e, p.1099
| USUAL CAUSES | USUAL INITIAL EVALUATION |
|---|---|
| Chlamydia trachomatis Neisseria gonorrhoeae Mycoplasma genitalium Ureaplasma urealyticum Trichomonas vaginalis Herpes simplex virus |
Demonstration of urethral discharge or pyuria Exclusion of local or systemic complications Urethral Gram’s stain to confirm urethritis, detect gram-negative diplococci Test for N. gonorrhoeae, C. trachomatis, M. genitalium (if indicated and available) |
| Initial Treatment for Patient and Partners | |
| Management of Recurrence | |
| Confirm objective evidence of urethritis. If patient was reexposed to untreated or new partner, repeat treatment of patient and partner. If patient was not reexposed, consider infection with T. vaginalisb or antibiotic- resistant M. genitaliumc, and treat accordingly (metronidazole for trichomoniasis; azithromycin for M. genitalium followed by moxifloxacin if needed). |
TABLE 141-5 Diagnostic Features and Management of Vaginal Infection FEATURE Etiology¶
Harrison's 22e, p.1101
| FEATURE | NORMAL VAGINAL EXAMINATION |
VULVOVAGINAL CANDIDIASIS | TRICHOMONAL VAGINITIS | BACTERIAL VAGINOSIS (BV) |
|---|---|---|---|---|
| Etiology | Uninfected; lactobacilli predominant |
Candida albicans | Trichomonas vaginalis | Associated with Gardnerella vaginalis, various anaerobic bacteria, and mycoplasmas |
| None | Vulvar itching and/or irritation | Profuse discharge; vulvar itching |
||
| Discharge | ||||
| Amount | Variable; usually scant | Scant | Often profuse | Moderate |
| Colora | Clear or translucent | White | White or yellow | White or gray |
| Consistency | Nonhomogeneous, flocculent |
Clumped; adherent plaques | Homogeneous | Homogeneous, low viscosity; uniformly coats vaginal walls |
| None | Erythema of vaginal epithelium, introitus; vulvar dermatitis, fissures common |
Erythema of vaginal and vulvar epithelium; colpitis macularis |
||
| pH of vaginal fluidb | Usually ≤4.5 | Usually ≤4.5 | Usually ≥5 | Usually >4.5 |
| None | None | May be present | ||
| Microscopyc | Normal epithelial cells; lactobacilli predominant |
Leukocytes, epithelial cells; mycelia or pseudomycelia in up to 80% of C. albicans culture–positive persons with typical symptoms |
Leukocytes; motile trichomonads seen in 80–90% of symptomatic patients, less often in the absence of symptoms |
Clue cells; few leukocytes; no lactobacilli or only a few outnumbered by profuse mixed microbiota, nearly always including G. vaginalis plus anaerobic species on Gram’s stain (Nugent’s score ≥7) |
| Isolation of Candida spp. | Isolation of T. vaginalis or positive NAATd |
|||
| Usual treatment | None | Azole cream, tablet, or suppository—e.g., miconazole (100-mg vaginal suppository) or clotrimazole (100-mg vaginal tablet) once daily for 7 days Fluconazole, 150 mg orally (single dose) |
Metronidazole or tinidazole, 2 g orally (single dose) Metronidazole, 500 mg PO bid for 7 days |
Metronidazole, 500 mg PO bid for 7 days Metronidazole gel, 0.75%, one applicator (5 g) intravaginally once daily for 5 days Clindamycin, 2% cream, one full applicator vaginally each night for 7 days |
| None | None; topical treatment if candidal dermatitis of penis is detected |
Examination for sexually transmitted infection; treatment with metronidazole, 2 g PO (single dose) |
TABLE 141-6 Combination Antimicrobial Regimens Recommended for Outpatient Treatment or for Parenteral Treatment of…¶
Harrison's 22e, p.1106
| OUTPATIENT REGIMENSa | PARENTERAL REGIMENS |
|---|---|
| Ceftriaxone (500 mg IM once) plus Doxycycline (100 mg PO bid for 14 days) plusb Metronidazole (500 mg PO bid for 14 days) |
Initiate parenteral therapy with either of the following regimens; continue parenteral therapy until 48 h after clinical improvement; then change to outpatient therapy, as described in the text Regimen A Cefotetan (2 g IV q12h) or cefoxitin (2 g IV q6h) plus Doxycycline (100 mg IV or PO q12h) Regimen B Clindamycin (900 mg IV q8h) plus Gentamicin (loading dose of 2 mg/kg IV or IM, then maintenance dose of 1.5 mg/kg q8h) |
TABLE 141-7 Clinical Features of Genital Ulcers FEATURE Incubation period Early primary lesions Number of lesions…¶
Harrison's 22e, p.1108
| FEATURE | SYPHILIS | HERPES | CHANCROID | LYMPHOGRANULOMA VENEREUM |
DONOVANOSIS |
|---|---|---|---|---|---|
| Incubation period | 9–90 days | 2–7 days | 1–14 days | 3 days–6 weeks | 1–4 weeks (up to 6 months) |
| Papule | Vesicle | Pustule | Papule, pustule, or vesicle | ||
| Number of lesions | Usually one | Multiple | Usually multiple, may coalesce |
Usually one; often not detected, despite lymphadenopathy |
Variable |
| 5–15 mm | 1–2 mm | Variable | 2–10 mm | ||
| Edges | Sharply demarcated, elevated, round, or oval |
Erythematous | Undermined, ragged, irregular |
Elevated, round, or oval | Elevated, irregular |
| Superficial or deep | Superficial | Excavated | Superficial or deep | ||
| Base | Smooth, nonpurulent, relatively nonvascular |
Serous, erythematous, nonvascular |
Purulent, bleeds easily | Variable, nonvascular | Red and velvety, bleeds readily |
| Firm | None | Soft | Occasionally firm | ||
| Pain | Uncommon | Frequently tender | Usually very tender | Variable | Uncommon |
| Firm, nontender, bilateral |
Firm, tender, often bilateral with initial episode |
Tender, may suppurate, loculated, usually unilateral |
Tender, may suppurate, loculated, usually unilateral |
TABLE 141-8 Initial Management of Genital or Perianal Ulcer Causative Pathogens HSV Treponema pallidum (primary…¶
Harrison's 22e, p.1109
- Causative Pathogens
- HSV
Treponema pallidum (primary syphilis)
Haemophilus ducreyi (chancroid) - Usual Initial Laboratory Evaluation
- Dark-field examination (if available), direct FA, or PCR for T. pallidum
RPR, VDRL, or EIA serologic test for syphilisa
Culture, direct FA, ELISA, or PCR for HSV
HSV-2-specific serology (consider)
In chancroid-endemic area: PCR or culture for H. ducreyi - Initial Treatment
- Herpes confirmed or suspected (history or sign of vesicles):
Treat for genital herpes with acyclovir, valacyclovir, or famciclovir. - Syphilis confirmed (dark-field, FA, or PCR showing T. pallidum, or RPR reactive):
Benzathine penicillin (2.4 million units IM once to patient, to recent [e.g., within
3 months] seronegative partner[s], and to all recent partners)b - Chancroid confirmed or suspected (diagnostic test positive, or HSV and syphilis
excluded, and persistent lesion):
Ciprofloxacin (500 mg PO as single dose) or
Ceftriaxone (250 mg IM as single dose) or
Azithromycin (1 g PO as single dose)