12.3 Sexually Transmitted Infections (STIs): CDC Guidelines, Screening & Partner Management
Key Takeaways
- Updated CDC STI Treatment Guidelines recommend Ceftriaxone 500 mg IM single dose (for body weight <150 kg; 1000 mg IM if >=150 kg) for uncomplicated anogenital and pharyngeal gonorrhea; if Chlamydia has not been excluded, add Doxycycline 100 mg PO BID for 7 days (azithromycin 1 g is no longer recommended for gonorrhea co-treatment).
- Primary syphilis presents with a solitary, indurated, PAINLESS chancre and non-tender lymphadenopathy; secondary syphilis presents with a generalized maculopapular rash involving the palms and soles, condylomata lata, and constitutional symptoms; treatment for primary, secondary, and early latent syphilis is Benzathine Penicillin G 2.4 million units IM single dose.
- Pelvic Inflammatory Disease (PID) is a clinical diagnosis requiring empiric treatment if a sexually active female has lower pelvic pain plus >=1 cervical motion tenderness ('chandelier sign'), uterine tenderness, or adnexal tenderness; outpatient therapy comprises Ceftriaxone 500 mg IM single dose + Doxycycline 100 mg PO BID x 14 days + Metronidazole 500 mg PO BID x 14 days.
- Genital ulcer differentiation: Syphilis (painless, clean base, indurated); HSV (multiple grouped painful vesicles/erosions on red base); Chancroid (painful, purulent dirty base with suppurative buboes); Lymphogranuloma Venereum (transient painless ulcer followed by painful matted 'groove sign' lymphadenopathy, treated with doxycycline x 21 days).
- HIV Pre-Exposure Prophylaxis (PrEP) with daily oral FTC/TDF (Truvada), FTC/TAF (Descovy, excluding receptive vaginal sex), or bimonthly IM Cabotegravir (Apretude) requires documented negative HIV-1/2 antigen/antibody testing within 1-2 weeks prior to initiation, baseline renal function, and HBV/HCV screening.
Last updated: August 2026
Sexually Transmitted Infections (STIs): CDC Guidelines, Screening & Partner Management
Sexually transmitted infections (STIs) represent a major public health epidemic across the adolescent, adult, and older adult populations. For the Adult-Gerontology Primary Care Nurse Practitioner (AGPCNP), clinical practice requires rigorous application of the latest CDC STI Treatment Guidelines, structured screening protocols (USPSTF), mastery of genital ulcer and discharge differentials, expedited partner therapy (EPT), and proactive delivery of HIV biomedical prevention (PrEP and PEP).
1. Universal Screening Recommendations (CDC / USPSTF)
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| EVIDENCE-BASED STI SCREENING PROTOCOLS (USPSTF & CDC) |
| |
| TARGET POPULATION SCREENING RECOMMENDATIONS & TESTING MODALITY |
| --------------------------------------------------------------------------------------------- |
| Sexually Active Females * ANNUAL Chlamydia trachomatis & Neisseria gonorrhoeae NAAT |
| Age < 25 Years * Urine NAAT or self-collected / clinician-collected vaginal swab |
| |
| Females Age >= 25 Years * Screen annually if at INCREASED RISK (new sex partner, multiple |
| partners, sex partner with concurrent partners/STI, sex work). |
| |
| All Adults & Adolescents * Universal opt-out HIV screening at least ONCE in lifetime |
| Age 13 to 64 Years * Screen at least ANNUALLY if high risk (MSM, IDU, commercial sex)|
| |
| Pregnant Individuals * First Prenatal Visit: Syphilis (serology), HIV, Hepatitis B |
| (HBsAg), Hepatitis C (anti-HCV), Chlamydia & Gonorrhea (if <25)|
| * 28 Weeks & Delivery: Repeat Syphilis & HIV if high risk. |
| |
| Men who have Sex with * At least ANNUALLY (every 3 to 6 months if high risk / on PrEP): |
| Men (MSM) - Syphilis serology (RPR/VDRL or Treponemal test) |
| - HIV antigen/antibody test |
| - NAAT for Chlamydia & Gonorrhea at ALL EXPOSED ANATOMIC SITES: |
| * Urethral (urine NAAT) |
| * Rectal (rectal swab NAAT) |
| * Pharyngeal (pharyngeal swab NAAT - Gonorrhea focus) |
| |
| All Adults Age 18 to 79 * Universal Hepatitis C Virus (anti-HCV with reflex RNA) ONCE. |
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2. Genital Ulcer Diseases: Differential Diagnosis & CDC Guidelines
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| GENITAL ULCER COMPARATIVE MATRIX |
| |
| DISEASE ORGANISM & LESION CHARACTERISTICS ADENOPATHY & SIGNS CDC FIRST-LINE THERAPY |
| --------------------------------------------------------------------------------------------- |
| Primary Syphilis Treponema pallidum (spirochete). PAINLESS, bilateral Benzathine Penicillin G|
| Single, PAINLESS, indurated ulcer regional LAD; firm, 2.4 million units IM |
| with clean base and sharp borders. rubbery, non-tender.single dose. |
| |
| Genital Herpes HSV-1 / HSV-2 (DNA virus). PAINFUL, bilateral Oral Valacyclovir |
| (HSV) Multiple, grouped PAINFUL vesicles inguinal adenopathy; 1000 mg BID x 7-10d |
| on red base -> shallow erosions. systemic fever/pain.(Primary episode). |
| |
| Chancroid Haemophilus ducreyi (G- bacillus). PAINFUL, suppurative Azithromycin 1 g PO |
| PAINFUL, deep, friable, dirty inguinal buboes; single dose OR |
| ulcer with ragged undermined edges.erythematous skin. Ceftriaxone 250 mg IM. |
| |
| Lymphogranuloma Chlamydia trachomatis (L1, L2, L3).PAINFUL, coalescent Doxycycline 100 mg |
| Venereum (LGV) Transient, small PAINLESS ulcer inguinal/femoral LADPO BID for 21 DAYS! |
| (often unnoticed by patient). divided by Poupart's |
| ligament ("GROOVE SIGN"). |
| |
| Granuloma Klebsiella granulomatis (G-). No true adenopathy; Azithromycin 1 g PO |
| Inguinale Painless, progressive, BEEFY-RED "Pseudobuboes" from weekly or 500 mg/d for |
| (Donovanosis) vascular ulcers that bleed easily. subcutaneous granulomas. >=3 weeks (healed)|
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Syphilis: Pathophysiological Stages, Serology & Protocols
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| SYPHILIS STAGING & CDC ANTIMICROBIAL PROTOCOLS |
| |
| [PRIMARY SYPHILIS] |
| - Painless indurated chancre at inoculation site + painless non-tender lymphadenopathy. |
| - Resolves spontaneously in 3 to 6 weeks without treatment. |
| | |
| v |
| [SECONDARY SYPHILIS (4 to 10 Weeks Post-Chancre)] |
| - Generalized non-pruritic MACULOPAPULAR RASH INVOLVING PALMS AND SOLES. |
| - CONDYLOMATA LATA: Flat, broad, moist, highly infectious whitish-gray plaques in warm skin folds.|
| - Patchy "moth-eaten" alopecia, mucous patches in oral cavity, diffuse lymphadenopathy, fever. |
| | |
| v |
| [LATENT SYPHILIS (Asymptomatic with Positive Serology)] |
| * Early Latent (<1 year duration): High risk of infectious recurrence. |
| * Late Latent (>=1 year duration or unknown timing): Non-infectious except via vertical/blood. |
| | |
| v |
| [TERTIARY SYPHILIS (Years to Decades Later)] |
| - Gummatous Syphilis (granulomatous destructive lesions of skin/bone), Cardiovascular Syphilis |
| (aortitis, aortic aneurysm), Neurosyphilis (Tabes dorsalis, Argyll Robertson pupils, paresis).|
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CDC Syphilis Antimicrobial Regimens:
- Primary, Secondary, or Early Latent (<1 year): Benzathine Penicillin G 2.4 million units IM as a single dose.
- Late Latent, Latent of Unknown Duration, or Tertiary with normal CSF: Benzathine Penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units).
- Neurosyphilis, Ocular Syphilis, or Otosyphilis: Aqueous Crystalline Penicillin G 18–24 million units IV daily, administered as 3–4 million units IV every 4 hours or continuous IV infusion for 10 to 14 days.
- Penicillin Allergy Management:
- Non-pregnant patients: Doxycycline 100 mg PO BID for 14 days (early) or 28 days (late).
- PREGNANCY WITH SYPHILIS & PENICILLIN ALLERGY: MANDATORY INPATIENT DESENSITIZATION TO PENICILLIN followed immediately by treatment with Benzathine Penicillin G. There are no safe or acceptable alternative antimicrobial regimens for syphilis in pregnancy!
- The Jarisch-Herxheimer Reaction: Acute febrile reaction with rigors, diaphoresis, headache, tachycardia, and exacerbation of cutaneous lesions occurring within 2 to 24 hours after initiating penicillin for syphilis. Caused by massive spirochete lysis and cytokine release (TNF-alpha, IL-6). Management: supportive care with antipyretics and patient reassurance. Crucial exam point: This is NOT a penicillin allergy and does NOT warrant discontinuing penicillin!
Syphilis Serological Testing Algorithms:
- Non-Treponemal Tests (RPR, VDRL): Measure antibodies against cardiolipin-lecithin-cholesterol antigen. Quantitative titers (e.g., 1:32) correlate with disease activity and are used to monitor treatment response. A four-fold decline in titer (e.g., from 1:32 down to 1:8, or 1:16 down to 1:4) at 6 to 12 months signifies successful therapeutic cure. False positives occur in SLE, antiphospholipid syndrome, pregnancy, IV drug use, advanced age, and acute viral infections.
- Treponemal Tests (FTA-ABS, TP-PA, CIA, EIA): Detect specific antibodies against T. pallidum. Qualitative (positive/negative); once positive, treponemal tests remain positive for life in >85% of individuals regardless of treatment success, and cannot be used to monitor cure or detect reinfection.
3. Urethritis, Cervicitis & Pelvic Inflammatory Disease (PID)
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| CERVICITIS & URETHRITIS: ETIOLOGY & UPDATED CDC MANAGEMENT |
| |
| PATHOGEN CLINICAL MANIFESTATIONS DIAGNOSTICS CDC 2021/2026 REGIMEN |
| --------------------------------------------------------------------------------------------- |
| Neisseria Purulent urethral/cervical NAAT (urine, vaginal, CEFTRIAXONE 500 MG IM |
| gonorrhoeae discharge, dysuria, inter- endocervical, rectal, SINGLE DOSE (for weight|
| (Gram-negative menstrual bleeding, PID. pharyngeal). Gram stain:<150 kg; 1000 mg IM if |
| diplococci) Disseminated DGI: triad of Gram-negative intra- weight >=150 kg). |
| polyarthralgia, tenosynovitis, cellular diplococci If Chlamydia not ruled |
| and pustular skin lesions. in polymorphonuclear WBC.out: add Doxycycline! |
| |
| Chlamydia Mucopurulent discharge or NAAT (first-catch urine DOXYCYCLINE 100 MG PO |
| trachomatis completely ASYMPTOMATIC in in men, self-collected BID FOR 7 DAYS |
| (Serovars D - K) up to 70% women, 50% men. vaginal swab in women - (First-line!). |
| Complications: PID, ectopic preferred over cervix). Pregnancy: Azithromycin|
| pregnancy, tubal infertility. 1 g PO single dose. |
| |
| Mycoplasma Persistent / recurrent non- Specific M. genitalium Two-Stage Regimen: |
| genitalium gonococcal urethritis (NGU) NAAT (macrolide Doxycycline 100mg BID |
| (Lacks cell wall) or cervicitis failing doxy. resistance testing). x 7d -> FOLLOWED BY |
| Moxifloxacin 400mg x 7d|
| |
| Trichomonas Copious frothy yellow-green NAAT (gold standard) or METRONIDAZOLE 500 MG |
| vaginalis malodorous discharge, pruritus,wet mount (motile PO BID FOR 7 DAYS |
| (Protozoan) "STRAWBERRY CERVIX" (petechiae).flagellated protozoa). in women! Treat partner|
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Pelvic Inflammatory Disease (PID): Diagnosis & Management
- Clinical Diagnostic Threshold (CDC): In any sexually active young female presenting with lower pelvic/abdominal pain, initiate empiric PID therapy immediately if one or more of the following minimum clinical criteria are present on bimanual pelvic examination, with no other cause identified:
- Cervical Motion Tenderness ("Chandelier Sign")
- Uterine Tenderness
- Adnexal Tenderness
- Additional Supporting Criteria: Oral temperature $>38.3^\circ\text{C}$ ($101^\circ\text{F}$), abnormal mucopurulent cervical discharge or cervical friability, abundant WBCs on saline wet mount, elevated ESR or CRP, and laboratory documentation of cervical N. gonorrhoeae or C. trachomatis.
- Outpatient Antimicrobial Regimen:
- Ceftriaxone 500 mg IM in a single dose (1000 mg if $\ge 150\text{ kg}$)
- + Doxycycline 100 mg PO BID for 14 days
- + Metronidazole 500 mg PO BID for 14 days (provides mandatory anaerobic coverage and treats comorbid bacterial vaginosis/trichomoniasis).
- Hospital Admission Criteria for Inpatient IV Therapy:
- Surgical emergencies (e.g., appendicitis, ovarian torsion) cannot be excluded.
- Tubo-ovarian abscess (TOA) suspected or confirmed on transvaginal ultrasound.
- Pregnancy.
- Severe illness, high fever, nausea, vomiting, or peritonitis.
- Inability to tolerate or lack of clinical improvement after 48–72 hours of outpatient oral therapy.
4. Vaginitis Syndromes: Clinical & Microscopic Differentiation
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| VAGINITIS SYNDROMES COMPARISON |
| |
| CRITERIA BACTERIAL VAGINOSIS (BV) TRICHOMONIASIS CANDIDA VULVOVAGINITIS |
| --------------------------------------------------------------------------------------------- |
| Pathophysiology Polymicrobial dysbiosis; loss Trichomonas vaginalis Candida albicans |
| of Lactobacillus; overgrowth (flagellated protozoan; (fungal overgrowth; |
| of Gardnerella & anaerobes. sexually transmitted). not sexually transmitted)|
| |
| Discharge Thin, homogeneous, off-white / Copious, frothy, Thick, white, curdy, |
| Appearance gray; smoothly coats walls. yellow-green, malodorous."cottage cheese-like".|
| |
| Symptoms "Fishy" malodor, worse after Pruritus, dysuria, Severe vulvar pruritus,|
| intercourse/menses; no itch. dyspareunia, soreness. burning, vulvar erythema|
| |
| Vaginal pH ELEVATED (>4.5) ELEVATED (>4.5) NORMAL (<=4.5) |
| |
| 10% KOH Whiff POSITIVE (sharp amine fishy POSITIVE or negative NEGATIVE (no amine odor)|
| Test odor upon adding 10% KOH). |
| |
| Microscopy CLUE CELLS (>20% squamous MOTILE FLAGELLATED PSEUDOHYPHAE and |
| (Wet Mount) epithelial cells covered in TRICHOMONADS + abundant budding yeast spores on|
| bacteria; obscured borders). PMN leukocytes. 10% KOH preparation. |
| |
| CDC Treatment Metronidazole 500 mg PO BID Metronidazole 500 mg PO Fluconazole 150 mg PO |
| Regimen x 7 days OR Metronidazole BID x 7 days (females); single dose (or topical|
| 0.75% vaginal gel QHS x 5 days.TREAT ALL SEX PARTNERS! clotrimazole/miconazole)|
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5. Human Papillomavirus (HPV) & Genital Warts
- Viral Genotypes:
- Low-Risk Non-Oncogenic Types (6 and 11): Cause $>90%$ of Condylomata Acuminata (genital warts: soft, fleshy, sessile, verrucous or cauliflower-like exophytic papules on the vulva, perineum, perianal region, penis, or scrotum).
- High-Risk Oncogenic Types (16, 18, 31, 33, 45, 52, 58): Account for $>70%$ of cervical, anogenital (vulvar, vaginal, penile, anal), and oropharyngeal squamous cell carcinomas.
- Treatment of Genital Warts:
- Patient-Applied: Imiquimod 5% cream (applied QHS 3 times/week for up to 16 weeks; stimulates local toll-like receptor 7 interferon release), Podofilox 0.5% solution/gel (applied BID for 3 consecutive days followed by 4 days off).
- Provider-Administered: Liquid nitrogen cryotherapy (repeated every 1–2 weeks), Trichloroacetic Acid (TCA 80%–90%) (safe in pregnancy!), surgical excision, or electrosurgery.
- HPV 9-Valent Vaccine (Gardasil 9): Indicated for all males and females through age 26 (and adults 27–45 via shared clinical decision-making). Dosing schedule: 2 doses at 0 and 6–12 months if series initiated before 15th birthday; 3 doses at 0, 1–2, and 6 months if initiated at $\ge 15\text{ years}$ or in immunocompromised patients.
6. Partner Management, EPT, and HIV Prevention (PrEP/PEP)
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| EXPEDITED PARTNER THERAPY & HIV BIOMEDICAL PREVENTION |
| |
| [EXPEDITED PARTNER THERAPY (EPT)] |
| - Clinical practice of treating sex partners of patients diagnosed with Chlamydia or Gonorrhea |
| by providing prescriptions or medication directly to the index patient to give to partners, |
| WITHOUT prior clinical examination of the partner by the provider. |
| - Strongly endorsed by CDC for heterosexually transmitted Chlamydia and Gonorrhea. |
| - Patient counseling: Partners must abstain from sexual activity until 7 days after completing |
| antimicrobial therapy and symptom resolution. |
| | |
| v |
| [HIV PRE-EXPOSURE PROPHYLAXIS (PrEP)] |
| * Daily Oral FTC / TDF (Truvada - Emtricitabine 200mg + Tenofovir Disoproxil Fumarate 300mg): |
| - Approved for all at-risk adults (MSM, heterosexual men/women, IDU) with CrCl >=60 mL/min. |
| * Daily Oral FTC / TAF (Descovy - Emtricitabine 200mg + Tenofovir Alafenamide 25mg): |
| - Approved for MSM and transgender women with CrCl >=30 mL/min. |
| - NOT APPROVED for cisgender women engaging in receptive vaginal intercourse! |
| * Long-Acting Injectable Cabotegravir (Apretude 600mg IM every 2 months): |
| - Gluteal IM injection every 2 months following two 1-month loading doses. |
| * Baseline & Monitoring Protocol for PrEP: |
| - MANDATORY: Document negative HIV-1/2 Ag/Ab test within 1-2 weeks prior to starting PrEP! |
| - Baseline: eGFR/serum creatinine, HBsAg, anti-HBs, anti-HCV, pregnancy test, STI NAATs. |
| - Every 3 Months: HIV Ag/Ab test, pregnancy test, STI NAAT screening. |
| - Every 6 Months: Serum creatinine / eGFR (assess tenofovir nephrotoxicity). |
| | |
| v |
| [HIV POST-EXPOSURE PROPHYLAXIS (PEP / nPEP)] |
| - Emergent 28-day antiretroviral course initiated as soon as possible, ideally within 2 hours |
| and NO LATER THAN 72 HOURS following high-risk occupational or sexual/injection exposure. |
| - 3-Drug Regimen: TDF/FTC (Truvada) once daily + Dolutegravir (Tivicay 50mg) once daily |
| OR Bictegravir/FTC/TAF (Biktarvy) once daily for EXACTLY 28 DAYS. |
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7. Board-Yield Summary & Clinical Pearls
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| ANCC AGPCNP CLINICAL EXAM PEARLS |
| |
| - CDC Gonorrhea Treatment Update: Prescribe CEFTRIAXONE 500 MG IM single dose (1000 mg IM if |
| weight >=150 kg). Azithromycin 1 g is NO LONGER recommended for gonorrhea due to resistance; |
| add oral Doxycycline 100 mg BID for 7 days if Chlamydia has not been excluded. |
| |
| - Primary Syphilis Chancre is strictly PAINLESS with a clean indurated base and non-tender LAD. |
| Secondary Syphilis features non-pruritic maculopapular rash on PALMS & SOLES and CONDYLOMATA |
| LATA. Treatment is BENZATHINE PENICILLIN G 2.4 million units IM single dose. |
| |
| - In a Pregnant Patient with Syphilis and a true Penicillin Allergy: MANDATORY HOSPITAL |
| ADMISSION FOR PENICILLIN DESENSITIZATION and treatment with Benzathine Penicillin G! No other |
| antimicrobial class is curative for fetal congenital syphilis. |
| |
| - Minimum criteria to treat PID: Sexually active female + pelvic pain + Cervical Motion |
| Tenderness (Chandelier sign), Uterine tenderness, OR Adnexal tenderness on bimanual exam. |
| Outpatient regimen: Ceftriaxone 500 mg IM + Doxycycline 100 mg BID x 14d + Metronidazole |
| 500 mg BID x 14d. |
| |
| - Trichomoniasis treatment in women is METRONIDAZOLE 500 MG BID FOR 7 DAYS (superior to single |
| 2 g dose); MUST treat all sexual partners simultaneously! Warn about disulfiram reaction with |
| alcohol. |
| |
| - Descovy (FTC/TAF) is NOT approved for HIV PrEP in individuals at risk from receptive vaginal |
| sex due to insufficient drug concentration in cervicovaginal tissues. Use Truvada (FTC/TDF). |
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Test Your Knowledge
A 24-year-old male presents to the clinic reporting a 3-day history of burning with urination and a copious, thick, yellowish-green urethral discharge. He reports having condomless sexual intercourse with a new female partner 6 days ago. Microscopic examination of the urethral exudate reveals numerous polymorphonuclear leukocytes with intracellular Gram-negative diplococci. His body weight is 78 kg. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis is pending. According to the current CDC STI Treatment Guidelines, which of the following represents the most appropriate initial pharmacological management?
A
B
C
D
Test Your Knowledge
A 22-year-old sexually active female presents to the primary care clinic reporting a 4-day history of bilateral lower abdominal aching, mild nausea, and abnormal yellowish vaginal discharge. Her last menstrual period ended 5 days ago. Vital signs: BP 118/74 mmHg, HR 82 bpm, Temp 38.4°C (101.1°F). On speculum examination, purulent discharge is seen exuding from the cervical os, and the cervix is friable. On bimanual examination, the patient exhibits severe pain and flinches upon gentle lateral motion of the cervix (positive cervical motion tenderness / chandelier sign) and moderate bilateral adnexal tenderness. Urine pregnancy test is negative. She is tolerating fluids and has no peritoneal signs. What is the most appropriate next step in clinical management?
A
B
C
D
Test Your Knowledge
A 28-year-old pregnant female at 14 weeks gestation presents for her initial prenatal visit. Routine serological screening reveals a reactive RPR with a quantitative titer of 1:64, and reflex treponemal testing (TP-PA) is positive. She denies any history of prior syphilis or previous treatment. Physical examination reveals a healing, non-tender ulcer on the right labium majus. The patient provides a documented history of severe IgE-mediated anaphylaxis to penicillin (hives, throat tightness, and hypotension requiring epinephrine at age 12). Which of the following is the most appropriate clinical management plan for this patient?
A
B
C
D