Neurosyphilis Treatment Outcomes After Intravenous Penicillin G Versus Intramuscular Procaine Penicillin Plus Oral Probenecid

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Data comparing neurosyphilis treatment regimens are limited.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Participants were enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis that was conducted at the University of Washington between April 2003 to May 2014. They were diagnosed with syphilis and referred by their providers due to concerns for neurosyphilis. We evaluated 150 people with CSF abnormalities who were treated with either intravenous aqueous penicillin G (PenG) or intramuscular aqueous procaine penicillin G plus oral probenecid (APPG-P). An abnormal CSF diagnosis was defined as a white blood cell (WBC) count &amp;gt;20/µL, a CSF protein reading &amp;gt;50 mg/dL, or a reactive CSF–Venereal Disease Research Laboratory test (VDRL). Hazard ratios for normalization of CSF or serum measures were determined using Cox regression.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In individuals treated with either PenG or APPG-P, CSF WBCs and CSF-VDRL reactivity normalized within 12 months after treatment, while protein normalized more slowly and less completely. There was no relationship between treatment regimen or human immunodeficiency virus (HIV) status and likelihood of normalization of any measure. Among those living with HIV, CSF WBC counts and CSF-VDRL reactivity were more likely to normalize in those treated with antiretrovirals. Unexpectedly, CSF WBCs were more likely to normalize in those with low CD4+ T cell counts. When neurosyphilis was more stringently defined as a reactive CSF-VDRL, the relationship with the CD4+ T cell count remained unchanged.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In the current antiretroviral treatment era, neurosyphilis treatment outcomes are not different for PenG and APPG-P, regardless of HIV status. The relationship between the normalization of CSF WBC counts and CD4+ T cell counts may indicate continued imprecision in neurosyphilis diagnostic criteria, due to HIV-related CSF pleocytosis.</jats:p> </jats:sec>

The Intersection of HIV and Syphilis: Update on the Key Considerations in Testing and Management

“…Intravenous aqueous penicillin has long been the mainstay of therapy; despite few studies to support its use, we know it reaches treponemicidal concentrations in the CSF, and has been a reliable therapy for decades. Intramuscular procaine penicillin, administered with probenecid, is also a recommended alternative regimen by the CDC and European guidelines [50,51], and a recent study by Dunaway et al suggested it is equivalent to intravenous aqueous penicillin G, regardless of HIV status [95]. Ceftriaxone is a common alternative regimen that can be used in most people with penicillin allergy, but a recent Cochrane review identified minimal evidence to support its use [96].…”

Syphilitic Outer Retinopathy: A Case Report and Review of the Literature

“…3 However, a recent study at the University of Washington of 150 individuals with neurosyphilis showed there to be no difference in clinical outcomes regardless of the route of penicillin administration. 13 The dosage of procaine penicillin G used for the Washington study was 2.4 U administered intramuscularly every 24 hours for 10 to 14 days, along with probenecid (0.5 g orally, 4 times daily). 13 Notably, 2 patients with SOR were treated successfully with IV ceftriaxone for 10 and 14 days, respectively.…”

“…13 The dosage of procaine penicillin G used for the Washington study was 2.4 U administered intramuscularly every 24 hours for 10 to 14 days, along with probenecid (0.5 g orally, 4 times daily). 13 Notably, 2 patients with SOR were treated successfully with IV ceftriaxone for 10 and 14 days, respectively. 7,8 Although ceftriaxone may be a valuable alternative for treating ocular syphilis and neurosyphilis in patients who are allergic to penicillin, a failure rate of 23% has been noted, specifically in HIV-infected patients.…”

cRGDyK‑modified procaine liposome inhibits the proliferation and motility of glioma cells via the ERK/p38MAPK pathway

“…Procaine is a type of local anesthetic (29). Procaine is used for local, regional and neuraxial anesthesia, and despite the emergence of several new anesthetic drugs, it remains a widely used anesthetic (30). Interestingly, procaine has also been revealed to have antitumor effects (31).…”