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Effective Alternative Treatment Regimens for People with Infectious Syphilis: A Systematic Review and Network

Anna Cvetkovic1, Laura Erdman2, Rochelle Johnstone3

  • 1Department of Medicine, Division of Infectious Diseases, McMaster University, Hamilton, Ontario, Canada.

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Summary

Rising syphilis rates and penicillin shortages necessitate alternative treatments. Doxycycline shows promise as a viable alternative to benzathine penicillin for infectious syphilis, despite low-quality evidence.

Keywords:
doxycyclinenetwork meta-analysispenicillinsyphilistreatment

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Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Public Health

Background:

  • Increasing incidence of syphilis globally.
  • Shortages of benzathine penicillin, the primary treatment.
  • Need for evidence-based alternative syphilis treatment regimens.

Purpose of the Study:

  • To systematically review and synthesize evidence on alternative treatments for infectious syphilis.
  • To compare the efficacy of various syphilis treatment regimens.

Main Methods:

  • Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).
  • Meta-analysis (MA) of observational studies.
  • Searched MEDLINE and EMBASE (2021-2025), including prior reviews.

Main Results:

  • 14 RCTs and 20 observational studies included; 13 RCTs in NMA (1,623 participants, 10 treatments).
  • Doxycycline showed a favorable point estimate compared to standard of care in NMA (OR 6.88).
  • Evidence quality was low for RCTs and very low for observational studies.

Conclusions:

  • Doxycycline is the most supported alternative to benzathine penicillin for syphilis treatment.
  • Low-quality evidence necessitates cautious interpretation.
  • Further high-quality research is warranted.