Antibiotic therapy for adults with neurosyphilis
Open accessAbstract
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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Aqueous crystalline penicillin G crosses the inflamed blood-brain barrier more effectively than benzathine penicillin G.
“which crosses the inflamed blood-brain barrier more effectively than benzathine penicillin G (44, 45).”
From Efectividad del tratamiento de la sífilis gestacional en el último trimestre sobre la incidencia de sífilis congénita: revisión sistemática y metanálisis (2025) · cites this paper as [45]
In “How the intervention might work” (page unavailable), the review says inflammation increases penicillin penetration into cerebrospinal fluid. In “Description of the intervention β-lactam antibiotics” (page unavailable), it recommends crystalline penicillin for neurosyphilis and says benzathine penicillin produces CSF levels too low to eliminate T. pallidum. It does not directly compare how effectively the two preparations cross an inflamed blood-brain barrier. (LLM, conf=0.82)
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- randomly.ab. Embase.com (Elsevier) 1. 'neurosyphilis'/exp 2. neurosyphilis:ab,ti 3. (lues NEAR/5 cerebrospinalis):ab,ti 4. (nervous NEAR/5 syphilis):ab,ti 5. neurolues:ab,ti 6. (syphilis):ab,ti AND (nervous NEAR/5 system):ab,ti 7. (syphilis NEAR/5 cns):ab,ti 8. 'tabes dorsalis'/exp 9. (tabes NEAR/5 dorsalis):ab,ti 10. (tabes NEAR/5 spinalis):ab,ti 11. myelosyphilis:ab,ti 12. (spinal NEAR/5 syphilis):ab,ti 13. or/1-12 14. 'antiinfective agent'/exp 15. antiinfective*:ab,ti 16. (anti NEAR/5 infective*):ab,ti 17. antibacterial*:ab,ti 18. (anti NEAR/5 bacterial*):ab,ti 19. antimicrobial*:ab,ti 20. (anti NEAR/5 microbial*):ab,ti 21. 'antimicrobial therapy'/exp 22. 'antibiotic agent'/exp 23. antibiotic*:ab,ti 24. 'bactericide'/exp 25. bactericid*:ab,ti 26. bacteriocid*:ab,ti 27. 'microbicide'/exp 28. microbicid*:ab,ti 29. 'beta lactam'/exp 30. 'penicillin derivative'/exp 31. 'penicillin G'/exp 32. 'procaine penicillin'/exp 33. 'benzathine penicillin'/exp 34. 'penicillin G potassium plus probenecid'/exp 35. 'amoxicillin'/exp 36. 'beta lactam':ab,ti 37. penicilli*:ab,ti 38. amoxicillin:ab,ti 39. 'cephalosporin derivative'/exp 40. cephalosporin*:ab,ti 41. 'ce riaxone'/exp 42. ce riaxon*:ab,ti 43. 'tetracycline derivative'/exp 44. 'tetracycline'/exp 45. tetracyclin*:ab,ti 46. 'doxycycline'/exp 47. doxycycline:ab,ti 48. 'minocycline'/exp 49. minocycline:ab,ti 50. 'glycylcycline derivative'/exp 51. glycylcycline:ab,ti 52. 'tigecycline'/exp Cochrane Database of Systematic Reviews 53. tigecycline:ab,ti 54. 'macrolide'/exp 55. macrolide*:ab,ti 56. 'erythromycin'/exp 57. erythromycin:ab,ti 58. 'azithromycin'/exp 59. azithromycin:ab,ti 60. 'clarithromycin'/exp 61. clarithromycin:ab,ti 62. 'ketolide'/exp 63. ketolide*:ab,ti 64. 'telithromycin'/exp 65. telithromycin:ab,ti 66. or/14-66 67.1 'randomised controlled trial'/exp 67.2 'single blind procedure'/exp 67.3 'double blind procedure'/exp 67.4 'crossover procedure'/exp 67.5 #36.1 OR #36.2 OR #36.3 OR #36.4 67.6 random*:ab,ti 67.7 placebo*:ab,ti 67.8 allocat*:ab,ti 67.9 crossover*:ab,ti 67.10 'cross over':ab,ti 67.11 trial:ti 67.12 (doubl* NEXT/1 blind*):ab,ti 67.13 #67.6 OR #67.7 OR #67.8 OR #67.9 OR #67.10 OR #67.11 OR #67.12 67.14 #67.5 OR #67.13 67.15 'animal'/de 67.16 'animal experiment'/de 67.17 'nonhuman'/de 67.18 #67.15 OR #67.16 OR #67.17 67.19 'human'/de 67.20 #67.18 AND #67.19 67.21 #67.18 NOT #67.20 67.22 #67.14 NOT #67.21 68. #13 AND #66 AND #67 AND [embase]/lim LILACS (iAHx interface) (mh:("Neurosyphilis")) OR (ti:("neurosyphilis")) OR (ab:("neurosyphilis")) AND db:("LILACS") AND type_of_study:("clinical_trials") WHO International Clinical Trials Registry Platform ICTRP portal neurosyphilis OR tabes dorsal ClinicalTrials.gov neurosyphilis OR tabes dorsal 2 neurosyphilis.tw. (1878) 3 (lues adj5 cerebrospinal).tw. (5) 4 (nervous adj5 syphilis).tw. (105) 5 neurolues.tw. (31) 6 (syphilis adj5 nervous adj5 system).tw. (93) 7 (syphilis adj5 cns).tw. (21) 8 exp Tabes Dorsalis/ (698) 9 (tabes adj5 dorsalis).tw. (271) 10 (tabes adj5 spinalis).tw. (0) 11 myelosyphilis.tw. (0) 12 (spinal adj5 syphilis).tw. (25) 13 or/1-12 (4155) 14 exp Anti-Bacterial Agents/ (695595) 15 anti bacterial$.tw. (2405) 16 antibacterial$.tw. (57619) 17 antibiotic$.tw. (272269) 18 bacteriocid$.tw. (533) 19 bactericid$.tw. (26584) 20 exp Anti-Infective Agents/ (1556656) 21 anti infective$.tw. (3308) 22 antiinfective$.tw. (426) 23 microbicid$.tw. (5471) 24 antimicrobial$.tw. (122743) 25 anti microbial$.tw. (2972) 26 exp beta-Lactams/ (124482) 27 exp Penicillins/ (78933) 28
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- Authors
- Buitrago-Garcia, D., Martí-Carvajal, A. J., Jimenez, A., Conterno, L. O., & Pardo, R.
- Affiliations
- Universidad Tecnológica Equinoccial; Cochrane Ecuador. Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo; Quito Ecuador
- Cochrane (GB)
- Fundación Universitaria de Ciencias de la Salud-Hospital de San José; Microbiology-Infectious Diseases; Calle 10 # 18-35 Bogota Colombia
- University of Campinas; Division of Infectious Diseases, Department of Internal Medicine,School of Medicine,; Rua Tessália Vieira de Camargo, 126 Cidade Universitária "Zeferino Vaz" Distrito de Barão Geraldo São Paulo Brazil 13083-887
- Universidad Nacional de Colombia (CO)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2019-05-27
- Volume
- 2019
- Issue
- 5
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- OpenAlex
- W4232811997
- Cited by
- 30
- References
- 77
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 3 · 2022: 11 · 2021: 3 · 2020: 1 · 2019: 2
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Syphilis Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- neurosyphilis, Treponema pallidum, antibiotic therapy, penicillin G, ceftriaxone, penicillin allergy, serological cure, clinical cure, adverse events, HIV coinfection, adults, tertiary syphilis, treatment effectiveness and safety, drug effectiveness
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