Abstract: 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. 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.

Plain-language summary: We searched the medical literature up to April 2019 for trials that evaluated the effectiveness and safety of drugs proposed for the management of neurosyphilis in adults. We found only one randomised clinical trial that met our criteria (patients are randomly put into groups to receive different treatments). This trial involved 36 adults with both syphilis and HIV, who were mainly men, with a median age of 34 years. The trial compared two drugs: ceftriaxone (2 g once daily), and penicillin G (4 million units every 4 hours for 10 days). It was funded by a pharmaceutical company. The trial reported serological cure, which is a decrease in the levels of the infection shown by laboratory analysis of fluids in the brain and spinal cord (known as cerebrospinal fluids), and clinical cure, which is the absence of signs or symptoms of neurosyphilis. Only three of 18 participants receiving ceftriaxone and two of 18 participants receiving penicillin G achieved serological cure; and eight of 18 participants receiving ceftriaxone and two of 18 participants receiving penicillin G achieved clinical cure. There was not enough evidence to allow us to state if there is a difference between treatment with ceftriaxone or Penicillin G for neurosyphilis in adults. The outcomes evaluated could change when trials with a better design become available. Additionally, we did not identify any evidence related to the effectiveness and safety of other drugs proposed to manage this condition. The quality of the evidence was very low for the outcomes serological cure and clinical cure due to problems with the trial's design and methods, and because there was only a small number of participants.