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. 2024 Mar 13;11(4):ofae142.
doi: 10.1093/ofid/ofae142. eCollection 2024 Apr.

Syphilis Treatment: Systematic Review and Meta-Analysis Investigating Nonpenicillin Therapeutic Strategies

Gustavo Yano Callado  1 , Maria Celidonio Gutfreund  1 , Isabele Pardo  1 , Mariana Kim Hsieh  1 , Vivian Lin  1 , Mindy Marie Sampson  2 , Guillermo Rodriguez Nava  2 , Tássia Aporta Marins  3 , Rodrigo Octávio Deliberato  4   5 , Marinês Dalla Valle Martino  1 , Marisa Holubar  2 , Jorge L Salinas  2 , Alexandre R Marra  1   6
Affiliations

Syphilis Treatment: Systematic Review and Meta-Analysis Investigating Nonpenicillin Therapeutic Strategies

Gustavo Yano Callado et al. Open Forum Infect Dis. .

Abstract

Background: Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis.

Methods: We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test.

Results: Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97-2.84]; I2 = 0%), azithromycin (0.92; [.73-1.18]; I2 = 0%), or doxycycline (0.82 [.61-1.10]; I2 = 1%) monotherapies with respect to serological conversion.

Conclusions: Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic.

Keywords: efficacy comparison; nonneurological syphilis; penicillin; syphilis treatment; treatment alternatives.

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Conflict of interest statement

Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Literature search for articles that evaluated the syphilis treatment alternatives against nonneurological syphilis. Abbreviation: CINAHL, Cumulative Index to Nursing and Allied Health Literature.
Figure 2.
Figure 2.
Forest plot of syphilis serological conversion after BPG monotherapy or doxycycline monotherapy [12, 17, 21, 24, 27, 31, 32, 34, 37]. Odds ratios (ORs) were determined using the Mantel-Haenszel random-effects method and are shown with 95% confidence intervals (CIs).
Figure 3.
Figure 3.
Forest plot of syphilis serological conversion after BPG monotherapy or ceftriaxone monotherapy [13, 15, 22, 24, 30]. Odds ratios (ORs) were determined with the Mantel-Haenszel random-effects method and are shown with 95% confidence intervals (CIs).
Figure 4.
Figure 4.
Forest plot of syphilis serological conversion after BPG monotherapy or azithromycin monotherapy [18–20, 25, 35]. Odds ratios (ORs) were determined with the Mantel-Haenszel random-effects method and are shown with 95% confidence intervals (CIs).
Figure 5.
Figure 5.
Forest plot of syphilis serological conversion after penicillin monotherapy or a strategy of treatment based on drug combinations [11, 14, 16, 20, 26, 36]. Odds ratios (ORs) were determined with the Mantel-Haenszel random-effects method and are shown with 95% confidence intervals (CIs).
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