Analysis of serological treatment response to doxycycline versus benzathine penicillin in syphilis infections, a retrospective single‐center study

Doxycilicine is the second‐line treatment of choice for infectious syphilis when treatment with penicillin G is not feasible. To date, difficulties in the penicillin supply chain make it necessary to evaluate and resort to antibiotic therapies which are currently considered a second‐line choice. Moreover, systematic studies comparing the two treatments in affected patients are still few, and many do not consider late and indeterminate latent infections. The objective of this study was to assess the differences in the serological response of the treatment of syphilis infections with benzathine penicillin compared with doxycycline. We built an in‐house database with all patients diagnosed with syphilis infection from January 2010 to January 2020 in the STD Centre of the S.Orsola‐Malpighi Polyclinic of the University of Bologna, located in the North‐east of Italy. We recorded all the principal independent (demographic, social status, reinfection rare, HIV infections, comorbidities, sexual behaviors, and initial TPHA values) and dependent variables (RPR values). We then extrapolated all patients treated with doxycycline (100 mg of doxycycline twice daily for 14 days for infections diagnosed within the first year and a 28 days course for infections older than 1 year or undetermined) and matched in 1:1 ratio numbers with a homogeneous group of patients treated with penicillin G (2.4 million units in a single dose intramuscularly for infections diagnosed within the first year and a cycle consisting in of 2.4 million units administered in a single dose per week for 3 weeks for infections older than 1 year or undetermined) We then analyzed the serological trends and outcomes in the primary, secondary and early latent groups versus late latent and undetermined infections. We retrieved 41 patients for each group with homogeneous initial characteristics. At the end of the 24‐month observation period, a slight difference in a valid RPR reduction rate emerged, with a greater success rate emerged in patients receiving penicillin than those with doxycycline (26 vs. 22, p 0.615). Indeed, patients with latent or indeterminate syphilis treated with doxycycline appear to have a higher rate of serofast than those treated with penicillin. Linear regression analysis showed no strong correlation between the analyzed independent variables and the observed outcomes. Doxycycline had a slightly lower, though not statistically different, success rate when compared with penicillin in treating primary syphilis, but appeared to have a reduced success rate in attaining resolution in late and undetermined syphilis infection.