How do you rule out a Sexually Transmitted Infection (STI)?

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Last updated: August 11, 2025View editorial policy

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Ruling Out Sexually Transmitted Infections (STIs)

To rule out STIs, comprehensive testing should include nucleic acid amplification tests (NAATs) for gonorrhea and chlamydia from all sites of potential exposure, wet mount and culture for trichomoniasis, and serologic testing for syphilis and HIV, with appropriate follow-up testing at 2 weeks and 12 weeks post-exposure.

Initial Evaluation and Specimen Collection

Specimen Collection by Site

  • Urogenital specimens:

    • Urine samples (first-void urine) for NAAT testing for gonorrhea and chlamydia 1
    • Vaginal swabs (can be self-collected) for women 2
    • Urethral swabs for men if symptomatic 3
  • Extragenital specimens (based on exposure history):

    • Pharyngeal specimens for gonorrhea culture (NAATs not FDA-approved for this site) 3
    • Rectal specimens for gonorrhea and chlamydia, especially important for men who have sex with men 3

Laboratory Testing

  1. Gonorrhea and Chlamydia:

    • NAAT testing is preferred due to high sensitivity (86.1%-100%) and specificity (97.1%-100%) 4
    • If chlamydial culture is unavailable, nonculture tests are acceptable, but positive results should be verified with a second test 3
  2. Trichomoniasis:

    • Wet mount and culture of vaginal swab specimens 3
    • Note: Microscopy sensitivity for T. vaginalis is only approximately 50%, so culture or antigen-based detection should be used for symptomatic patients with negative microscopy 3
  3. Bacterial Vaginosis and Yeast:

    • If vaginal discharge or malodor is present, wet mount should be examined for evidence of BV and yeast infection 3
  4. Syphilis:

    • Serologic testing using sequential testing for treponemal and nontreponemal antibodies 4
  5. HIV:

    • Initial serum sample should be preserved for subsequent analysis if follow-up serologic tests are positive 3

Follow-Up Testing Schedule

2-Week Follow-Up

  • Repeat cultures and wet mount tests if prophylactic treatment was not provided 3
  • This is critical because infectious agents may not have produced sufficient concentrations of organisms to result in positive tests at the initial examination 3
  • Test of cure is recommended for all cases of pharyngeal gonorrhea and for rectal chlamydia if treated with azithromycin 5

12-Week Follow-Up

  • Serologic tests for syphilis and HIV infection 3
  • If positive, testing of the sera collected at the initial examination will assist in determining whether the infection predated the exposure 3

Treatment Recommendations

Empiric Treatment for Common STIs

If high-risk exposure or symptoms are present, consider empiric treatment:

  • For gonorrhea:

    • Ceftriaxone 250 mg IM in a single dose (weight-based dosing per 2021 CDC guidelines) 6, 5
  • For chlamydia:

    • Doxycycline 100 mg orally twice daily for 7 days (preferred treatment per 2021 CDC guidelines) 7, 5
    • Alternative: Azithromycin 1 g orally in a single dose 8
  • For trichomoniasis:

    • Metronidazole 2 g orally in a single dose 3
    • For vaginal trichomoniasis, a seven-day regimen of metronidazole is now recommended 5

Special Considerations

Asymptomatic Infections

  • Approximately 70% of infections with trichomoniasis and 53%-100% of extragenital gonorrhea and chlamydia infections are asymptomatic 4
  • Screening based on risk factors rather than symptoms is essential, as most chlamydia infections and many gonorrhea infections are asymptomatic 1
  • In some studies, only 2% of individuals with positive tests reported symptoms 9

Testing Technology Advances

  • Self-collected specimens (urine or vaginal swabs) have made screening more accessible and less invasive 1
  • NAATs have revolutionized STI testing by allowing for non-invasive sample collection with high accuracy 2

Common Pitfalls to Avoid

  1. Relying solely on symptoms for diagnosis: The majority of STIs (81%-98%) would be undiagnosed and untreated using only symptomatology 9

  2. Missing extragenital infections: Failing to test pharyngeal and rectal sites based on sexual exposure history 3

  3. Inadequate follow-up: Low follow-up rates are a concern, with only 21% of infected individuals seeking medical care 10

  4. Improper specimen collection: Using the wrong collection technique or container can lead to false-negative results

  5. Not testing for all common STIs: Focusing only on gonorrhea and chlamydia while missing trichomoniasis, syphilis, or HIV

By following this comprehensive approach to STI testing, clinicians can effectively rule out infections, prevent complications, and reduce transmission in the community.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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