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TREATMENT OF NEUROSYPHILIS: IV PENICILLIN G VS IM PROCAINE PENICILLIN/ORAL PROBENECID
Shelia Dunaway1, Claire Maxwell2, Lauren Tantalo1, Sharon Sahi1, Arielle P. Davis1, Claire Stevens1, Abigail Crooks1, Christina Marra1
1Harborview Med Cntr, Seattle, WA, USA,2Univ of Washington, Seattle, WA, USA
The CDC recommends IV aqueous penicillin G (PenG) for 10-14 days to treat neurosyphilis (NS). IM aqueous procaine penicillin (APPG) plus oral probenecid is considered an alternative treatment that might be considered if compliance can be assured. APPG is preferable to PenG in some instances due to lower cost and greater convenience. We compare these 2 therapies for neurosyphilis.
Between April 2003 and May 2015, 150 individuals were enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis and were treated with PenG or APPG regimens for NS. They underwent follow-up CSF examinations and blood draws 3, 6, and 12 months after treatment. Relationships between categorical variables were determined by Chi square or Fisher exact test. Hazard ratios (HR) for normalization of CSF white blood cells (WBCs) (decline to <20/ul), CSF protein (decline to <50/mg/dl) and CSF-VDRL or serum RPR reactivity (4-fold decline or reversion to nonreactive) were determined using Cox regression.
Both groups were well matched; most were HIV-infected Caucasian men in their early 40s. More patients treated with APPG had early stage syphilis (71% vs 47%, p=0.01) and more were treated for uncomplicated syphilis within 90 days of study entry (43% vs 19%, p=0.01). There were no differences in pre-treatment serum RPR titer, CSF WBCs, CSF-VDRL reactivity, or proportion with symptomatic NS. More patients treated with PenG had elevated CSF protein (p=0.07). Normalization of all 4 measures did not differ in the 2 treatment groups, or in HIV-infected, or in those treated for uncomplicated syphilis before entry. CSF protein normalized more slowly in those with higher pre-treatment CSF concentration [HR=0.2, p <0.001]. CSF-VDRL normalized more slowly in late syphilis [HR=0.5, p <0.01] but normalized faster in symptomatic NS [HR=1.7, p <0.05]. Serum RPR normalized faster in those with higher pre-treatment titers [HR=2.3, p < 0.001] and in those with symptomatic NS [HR=1.5, p <0.05] and more slowly in late stage syphilis [HR=0.4, p <0.001]. Multivariate analysis, taking into account stage and previous treatment in addition to other significant univariate variables, revealed no relationship between normalization of any measure and treatment regimen.
We did not see a difference in treatment response between NS patients treated with PenG or APPG. Although treatment was not randomized, we continued to see no difference in response even after taking into account pre-treatment differences.