Sexually Transmitted Infections — Syndrome, Organism and Antibiotic Stewardship

The answer first

Sexually transmitted infections (STIs) are among the commonest reportable diseases worldwide, are major causes of infertility, adverse pregnancy outcome, cancer and death, and are uniquely shaped by the rise of antimicrobial resistance. The physician must move between the syndromic (urethritis, genital ulcer, pelvic inflammatory disease) and the aetological (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Mycoplasma genitalium, herpes simplex virus, human papillomavirus, HIV) approaches, choosing tests that change management and antibiotics that follow current resistance patterns. ^{[1] [2]}

A physician-level answer rests on four pillars: ^[1]

1. Treat by the CDC 2021 (or equivalent) guideline and verify the organism. Gonorrhoea is treated with ceftriaxone 500 mg IM as monotherapy for uncomplicated infection; chlamydia with doxycycline 100 mg orally twice daily for 7 days; syphilis by stage with benzathine penicillin G 2.4 million units IM; M. genitalium with an extended macrolide regimen or moxifloxacin when macrolide-resistant. ^{[1] [3] [4]}
2. Screen the asymptomatic at-risk patient and the partner. Annual nucleic acid amplification test (NAAT) screening for chlamydia and gonorrhoea in sexually active women under 25, in men who have sex with men, in pregnancy, and on PrEP enrolment; syphilis, HIV and hepatitis C serology in at-risk groups; treat partners by expedited partner therapy where permitted. ^[1]
3. Recognise the complications early. Pelvic inflammatory disease, ectopic pregnancy and tubal infertility from chlamydia and gonorrhoea; congenital syphilis; disseminated gonococcal infection; neurosyphilis; neonatal herpes; and HIV acquisition amplified by ulcerative STIs. ^{[2] [4] [5]}
4. Use PrEP, vaccination and behavioural prevention in parallel. HIV pre-exposure prophylaxis with tenofovir alafenamide-emtricitabine (or tenofovir disoproxil fumarate-emtricitabine) reduces sexual HIV acquisition by roughly 86 to 99 percent in adherent patients; HPV vaccination prevents cervical, anal and oropharyngeal cancer; condoms, partner notification and harm reduction complete the package. ^{[8] [9] [11]}

DWE high-yield: "Ceftriaxone alone, no azithromycin." The CDC 2021 gonorrhoea recommendation dropped routine dual therapy because of falling azithromycin susceptibility and rising ceftriaxone efficacy: ceftriaxone 500 mg IM as a single agent for uncomplicated urogenital, rectal and pharyngeal gonorrhoea (1 g for weights ≥ 150 kg). Add doxycycline 100 mg bd for 7 days only if chlamydia has not been excluded. ^{[1] [3]}

References12ShowHide

1. [1]Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep, 2021.PMID 34292926
2. [2]Unemo M, Seifert HS, Hook EW 3rd, et al. Gonorrhoea. Nat Rev Dis Primers, 2019.PMID 31754194
3. [3]Barbee LA, St Cyr SB Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines. Clin Infect Dis, 2022.PMID 35416971
4. [4]Chevalier FJ, Bacon O, Johnson KA, et al. Syphilis: A Review. JAMA, 2025.PMID 41100079
5. [5]Hamill MM, Ghanem KG, Tuddenham S State-of-the-Art Review: Neurosyphilis. Clin Infect Dis, 2024.PMID 37593890
6. [6]Wood GE, Bradshaw CS, Manhart LE Update in Epidemiology and Management of Mycoplasma genitalium Infections. Infect Dis Clin North Am, 2023.PMID 37105645
7. [7]Jensen JS, Unemo M Antimicrobial treatment and resistance in sexually transmitted bacterial infections. Nat Rev Microbiol, 2024.PMID 38509173
8. [8]Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet, 2020.PMID 32711800
9. [9]McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet, 2016.PMID 26364263
10. [10]Le Cleach L, Trinquart L, Do G, et al. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients. Cochrane Database Syst Rev, 2014.PMID 25086573
11. [11]Lei J, Ploner A, Elfström KM, et al. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med, 2020.PMID 32997908
12. [12]Hufstetler K, Llata E, Miele K, et al. Clinical Updates in Sexually Transmitted Infections, 2024. J Womens Health (Larchmt), 2024.PMID 38770770