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. 2019 May 27;5(5):CD011399.
doi: 10.1002/14651858.CD011399.pub2.

Antibiotic therapy for adults with neurosyphilis

Diana Buitrago-Garcia  1 , Arturo J Martí-Carvajal, Adriana Jimenez, Lucieni O Conterno, Rodrigo Pardo
Affiliations

Antibiotic therapy for adults with neurosyphilis

Diana Buitrago-Garcia et al. Cochrane Database Syst Rev. .

Abstract

Background: Neurosyphilis is an infection of the central nervous system, caused by Treponema pallidum, a spirochete capable of infecting almost any organ or tissue in the body causing neurological complications due to the infection. This disease is a tertiary manifestation of syphilis. The first-line treatment for neurosyphilis is aqueous crystalline penicillin. However, in cases such as penicillin allergy, other regimes of antibiotic therapy can be used.

Objectives: To assess the clinical effectiveness and safety of antibiotic therapy for adults with neurosyphilis.

Search methods: We searched the Cochrane Library, CENTRAL, MEDLINE, Embase, LILACS, World Health Organization International Clinical Trials Registry Platform and Opengrey up to April 2019. We also searched proceedings of eight congresses to a maximum of 10 years, and we contacted trial authors for additional information.

Selection criteria: We included randomised clinical trials that included men and women, regardless of age, with definitive diagnoses of neurosyphilis, including HIV-seropositive patients. We compared any antibiotic regime (concentration, dose, frequency, duration), compared to any other antibiotic regime for the treatment for neurosyphilis in adults.

Data collection and analysis: Two review authors independently selected eligible trials, extracted data, and evaluated risk of bias. We resolved disagreements by involving a third review author. For dichotomous data (serological cure, clinical cure, adverse events), we presented results as summary risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach.

Main results: We identified one trial, with 36 participants​ diagnosed ​with syphilis and HIV. The participants were mainly men, with a median age of 34 years. This trial, ​funded by a pharmaceutical company, compared ceftriaxone in 18 participants (2 g daily for 10 days), with penicillin G, also in 18 participants (4 million/Units (MU)/intravenous (IV) every 4 hours for 10 days). The trial reported incomplete and inconclusive results. Three of 18 (16%) participants receiving ceftriaxone versus 2 of 18 (11%) receiving penicillin G achieved serological cure (RR 1.50; 95% CI: 0.28 to 7.93; 1 trial, 36 participants very low-quality evidence); and 8 of 18 (44%) participants receiving ceftriaxone versus 2 of 18 (18%) participants receiving penicillin G achieved clinical cure (RR 4.00; 95% CI: 0.98 to 16.30; 1 trial, 36 participants very low-quality evidence). Although more participants who received ceftriaxone achieved serological and clinical cure compared to those who received penicillin G, the evidence from this trial was insufficient to determine whether there was a difference between treatment with ceftriaxone or penicillin G.In this trial, the authors reported what would usually be adverse events as symptoms and signs in the follow-up of participants. Furthermore, this trial did not evaluate recurrence of neurosyphilis, time to recovery nor quality of life. We judged risk of bias in this clinical trial to be unclear for random sequence generation, allocation, ​and blinding of participants, and high for incomplete outcome data, potential conflicts of interest (funding bias), and other bias, due to the lack of a sample size calculation. We rated the quality of evidence as very low.

Authors' conclusions: Due to low quality and insufficient evidence, it was not possible to determine whether there was a difference between treatment with ceftriaxone or Penicillin G. Also, the benefits to people without HIV and neurosyphilis are unknown, as is the ceftriaxone safety profile.Therefore, these results should be interpreted with caution. This conclusion does not mean that antibiotics should not be used for treating this clinical entity. This Cochrane Review has identified the need of adequately powered trials, which should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) recommendations, conducted and reported as recommended by the CONSORT statement. Furthermore, the outcomes should be based on patients' perspectives taking into account Patient-Centered Outcomes Research Institute (PCORI) recommendations.

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Conflict of interest statement

DB has no known conflicts of interest.

AMC has no known conflicts of interest.

AJ In 2016 and 2017 received payment for lectures from Procaps and Abbottt laboratories. This activity was not related to her work with The Cochrane Collaboration or any Cochrane Review.

LOC has no known conflicts of interest.

RP has no known conflicts of interest.

Figures

1
1
Flow of information through the different phases of the review
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
1.1
1.1. Analysis
Comparison 1 Ceftriaxone versus penicillin G, Outcome 1 Serological cure.
1.2
1.2. Analysis
Comparison 1 Ceftriaxone versus penicillin G, Outcome 2 Clinical cure.
1.3
1.3. Analysis
Comparison 1 Ceftriaxone versus penicillin G, Outcome 3 All causes of withdrawals.
See this image and copyright information in PMC

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