Correspondence

Minocycline for Symptomatic Neurosyphilis in Patients Allergic to Penicillin

N Engl J Med 1997; 337:1322-1324October 30, 1997

Article

To the Editor:

Treatment of symptomatic neurosyphilis is an increasingly common clinical problem because of its rising incidence, particularly in patients coinfected with the human immunodeficiency virus type 1 (HIV-1).1 The mainstay of treatment remains intravenous penicillin G at high dosage, ranging from 12 million to 24 million units given six times a day for 10 to 14 days.1 Treatment options for patients with neurosyphilis who are allergic to penicillin are limited. Such patients should undergo a skin test and hospitalization for a penicillin-desensitization protocol before intravenous penicillin administration.2,3 We know little, however, about the outcomes of high-dose penicillin G treatment for neurosyphilis in penicillin-allergic patients after desensitization.

Long-acting oral tetracyclines are recommended for patients with primary or secondary syphilis who are allergic to penicillin.1 Sufficient cerebrospinal fluid concentrations are obtained in healthy subjects and in patients with latent neurosyphilis.4

Three HIV-seronegative men were given a diagnosis of neurosyphilis. All three had extensive cutaneous rash consistent with a hypersensitivity reaction to penicillin, refused to undergo a desensitization procedure, and provided informed consent to be treated with minocycline according to the present protocol. They were given oral minocycline at a dose of 100 mg twice a day for 14 consecutive days per month for 9 months, with clinical, serologic, and cerebrospinal fluid examinations 6, 12, and 24 months after beginning treatment.

There were no drug-related side effects. Clinical symptoms and signs improved after only one month. Cerebrospinal fluid examination showed the disappearance of pleocytosis at 6, 12, and 24 months, as well as progressive normalization of protein concentrations in two cases. A Venereal Disease Research Laboratory test in cerebrospinal fluid became negative in two patients at six months (Table 1Table 1Results of Cerebrospinal Fluid Tests in Three Patients Allergic to Penicillin Whose Neurosyphilis was Treated with Oral Minocycline.). Patient 3 was noncompliant and only completed three cycles of treatment during the first 12 months.

Oral administration of long-acting tetracyclines according to the present protocol may represent an effective alternative treatment to penicillin desensitization for patients with neurosyphilis who are allergic to penicillin G.

Treatment of neurosyphilis in patients coinfected with HIV-1 may require the presence of treponemicidal concentrations in the central nervous system for longer periods than those provided by standard, high-dosage, intravenous penicillin G regimens. Given the poor response to standard intravenous penicillin G in some HIV-infected patients,5 intermittent, oral administration of long-acting tetracyclines may be a useful therapeutic strategy in patients with recurrence after a full course of intravenous penicillin G.

Andrea De Maria, M.D.
Claudio Solaro, M.D.
Michele Abbruzzese, M.D.
Alberto Primavera, M.D.
University of Genoa, 13164 Genoa, Italy

5 References

1. 1

   Tramont EC. Treponema pallidum (syphilis). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 4th ed. Vol. 2. New York: Churchill Livingstone, 1995:2117-33.
   

2. 2

   1993 Sexually transmitted diseases treatment guideline. MMWR Morb Mortal Wkly Rep 1993;42(RR-14).
   

3. 3

   Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med 1991;324:1785-1790
   Full Text | Web of Science | Medline

4. 4

   Yim CW, Flynn NM, Fitzgerald FT. Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis. Antimicrob Agents Chemother 1985;28:347-348
   Web of Science | Medline

5. 5

   Gordon SM, Eaton ME, George R, et al. The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection. N Engl J Med 1994;331:1469-1473
   Full Text | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Won-Keun Si, Kang-Heum Suh, Moon-Hyoung Lee, Bo-Kyoung Choi, Jin-Ah Hwang, Choon-Kwan Kim. (2011) Treatment of Neurosyphilis with Ceftriaxone in a Patient Infected with Human Immunodeficiency Virus. Infection and Chemotherapy 43:3, 262
   CrossRef

2. 2

   A. De Maria, A. Primavera. (2000) Possibility of the Use of Oral Long-Acting Tetracyclines in the Treatment of Lyme Neuroborreliosis. Clinical Infectious Diseases 31:3, 848-849
   CrossRef