Table 1.

State-of-the-art in the approach to treatment of STIs in Europe.^a

	Antibiotics with intrinsic proven activity in wild-type strains	Widespread antimicrobial resistant strains	Current first-line	Second line when allergy or treatment failure	Third line after treatment failure or resistance	Resistance guided therapy	Pregnancy	Empirical combination
Gonorrhoea	Penicillin, cephalosporins, carbapenems, tetracyclines, macrolides, aminoglycosides, and fluoroquinolones	Penicillin, fluoroquinolones, tetracyclines, macrolides	-Ceftriaxone 1 g IM as a single dose in settings where patients are likely to return for test of cure OR -Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose in non-well controlled settings	-Spectinomycin 2 g IM as a single dose together with azithromycin 2 g as a single oral dose -Ciprofloxacin 500 mg as a single oral dose in susceptible strains -Gentamicin 240 mg IM as a single dose together with azithromycin 2 g as a single oral dose -Ertapenem 1 g IM once daily for three days OR -Cefixime 400 mg as a single oral dose together with azithromycin 2 g as a single oral dose.	Guided by resistance testing	Quinolone susceptibility confirmed by molecular tests: -Ciprofloxacin 500 mg as a single oral dose Ceftriaxone resistance: -Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose -Spectinomycin 2 g IM as a single dose together with azithromycin 2 g as a single oral dose	-Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose	-Doxycycline 100 mg oral dose twice daily for 7 days given at the same time as ceftriaxone to cover C. trachomatis infection, if not excluded by molecular tests
Mycoplasma genitalium	Tetracyclines, macrolides, fluoroquinolones, and streptogramins	Macrolides, fluoroquinolones	-Azithromycin 500 mg on day one, then 250 mg on days 2–5 (oral) -Josamycin 500 mg 3 times daily for 10 days (oral)	-Moxifloxacin 400 mg od for 7 days (oral)	-Pristinamycin 1 g four times daily for 10 days (oral), 75% cure OR -Minocycline 100 mg two times daily for 14 days (oral), 70% cure OR -Doxycycline 100 mg two times daily for 14 days (oral), 40% cure	Initial syndromic treatment: -Doxycycline 100 mg bid, 7 days (while testing for macrolide resistance) Upon confirmation of macrolide-susceptibility: -Azithromycin 500 mg on day one, then 250 mg od days 2–5 (oral) Macrolide resistance: -Moxifloxacin 400 mg od for 7 days (oral)	-Azithromycin 500 mg on day one, then 250 mg on days 2–5 (oral) Macrolide-resistance: -Postpone treatment until delivery OR -Pristinamycin can be considered if symptomatic.
Syphilis	Penicillin, cephalosporins, macrolides, tetracyclines, oxazolidinones	Azithromycin	Primary, secondary, and early latent syphilis: -BPG 2.4 MUI IM as a single dose Late latent syphilis: -BPG 2.4 MUI IM weekly for 3 weeks Neurosyphilis: -Aqueous crystalline penicillin G 3 to 4 MUI IV every 4 h for 10–14 days. OR -Procaine penicillin G 2.4 million units IM once daily, plus probenecid 500 mg orally 4 times/day, both for 10–14 days	Primary, secondary, and early latent syphilis with penicillin allergy: -Doxycycline 100 mg orally twice daily for 14 days OR -Ceftriaxone (1 g IV or IM daily for 10–14 day) Late latent syphilis or neurosyphilis with penicillin allergy: -Penicillin allergy desensitization.			First line is BPG, in case of penicillin allergy: -Penicillin allergy testing and desensitization.

^aTreatment Guidelines (Europe): https://iusti.org/treatment-guidelines/-accessed 10 June 2023.

Similar Guidelines are available online: https://www.cdc.gov/std/treatment-guidelines/STI-Guidelines-2021.pdf (USA); https://sti.guidelines.org.au/ (Australia); https://www.bashh.org/guidelines (UK). BPG: Benzathine penicillin G.