The effectiveness of penicillin and non-penicillin alternatives in the treatment of syphilis: A literature review

Background: Syphilis is a sexually transmitted infection caused by Treponema pallidum, with more than seven million new cases annually worldwide. The standard therapy remains Benzathine penicillin G, but issues such as allergy, limited availability, and emerging antibiotic resistance necessitate an evaluation of non-penicillin alternatives.

Objective: This review aims to assess the effectiveness of penicillin and non-penicillin alternatives in the treatment of syphilis based on recent literature.

Methods: Articles were retrieved from PubMed, Scopus, and Google Scholar using the keywords “syphilis,” “penicillin,” “doxycycline,” “ceftriaxone,” and “azithromycin.” Publications from 2015 to 2024 were included if they discussed clinical outcomes of penicillin or non-penicillin therapy for syphilis.

Results: Penicillin remains the most effective therapy for all stages of syphilis, achieving cure rates above 95%. Doxycycline shows 85–90% efficacy, while ceftriaxone achieves 90–92% but requires parenteral administration. Azithromycin presents lower efficacy (70–80%) and higher resistance rates.

Conclusion: Benzathine penicillin G remains the gold standard for syphilis treatment. Doxycycline and ceftriaxone are effective alternatives for patients allergic to penicillin, whereas azithromycin is not recommended due to resistance concerns.