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Treatment of neurosyphilis with ceftriaxoneS Shann, J Wilson. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The first choice treatment for late syphilis is penicillin. Other tion or acute coronary ostitis. He received 1 g of ceftriaxone than doxycycline, which penetrates the CNS, there are few alternatives for the treatment of neurosyphilis. We report a He was reviewed 7, 19, and 36 months after treatment with repeat syphilis serology of blood and CSF (see table 1).
case of successful treatment of symptomatic neurosyphilis Clinically he made some improvement in terms of his The first choice treatment for late syphilis is penicillin.1 Therecommendedtreatmentforneurosyphilisispenicillin.
Other than doxycycline, which penetrates the CNS, there Doxycycline and amoxycillin have been evaluated as second are few alternatives for the treatment of neurosyphilis.
line options but as they are given orally, there may be We report a case of successful treatment of symptomatic adherence issues. The UK national guidelines2 and the neurosyphilis with parenteral ceftriaxone.
European guidelines for the management of syphilis3 donot recommend ceftriaxone for the treatment of late syphilis.
However, the CDC Sexually Transmitted Diseases Treatment Guidelines 20024 suggest that it may be used as an alternative A 61 year old heterosexual man who had served in the armed in penicillin allergic patients with neurosyphilis.
forces abroad was referred to the department of genitour- Ceftriaxone has been proved to have good CNS penetra- inary medicine with a diagnosis of symptomatic neurosyphi- tion. A dose of 1 g daily achieves levels well above the MIC for Treponema pallidum of 0.0006 mg/ml.5 It also differs from Six months before this he had been admitted to hospital other cephalosporins by having an unusually long serum half with a history of expressive dysphasia and a left sided hemiparesis. His behaviour had been noted to be ‘‘out of However there have been reports that intramuscular character’’ for a week before the admission. A computed ceftriaxone may not be adequate treatment for neurosyphi- tomograph (CT) scan revealed patchy ischaemic change, lis.5 A retrospective study of HIV infected individuals treated especially of the left frontal lobe. A carotid duplex scan and with ceftriaxone for asymptomatic neurosyphilis or latent ECG were normal but an echocardiogram revealed a trivial syphilis revealed a 23% failure rate.7 Another study suggested degree of aortic regurgitation. His neurological abnormalities that intravenous ceftriaxone may be an alternative to resolved over several days and he was discharged.
penicillin for treatment of HIV infected patients with neuro- In June 1997 he was reviewed in the neurology outpatient syphilis complicating early syphilis infection. However, in clinic with a history of transient dysphasia and impaired use this setting, disease may be confined to the meninges and of his right hand. He had developed marked short termmemory loss and was unable to perform simple tasks. Onexamination he was generally tremulous and dysarthric but Table 1 Blood and CSF parameters before and after with normal tendon reflexes, tone, power, pain, and vibration sensation and proprioception. A magnetic resonance imaging (MRI) scan revealed generalised prominence of CSF spacesdisproportionate to the patient’s age and small vessel ischaemic damage within both frontal lobes.
He was readmitted to hospital in August 1997 with a history of frequent falls. He was confused and had delusions of persecution. Investigations revealed positive syphilis serology in blood and CSF (see table 1) and he was referred to the department of genitourinary medicine.
A diagnosis of untreated symptomatic neurosyphilis was made with both cerebrovascular components and parenchy- matous features of general paresis. He had a history of anaphylaxis with penicillin and there were concerns about non-compliance with doxycycline. We decided to use ceftriaxone because of its good CNS penetration. There is a 10% risk of cross sensitivity between penicillin and cepha- losporins; therefore, he was admitted to hospital and given a test dose of 50 mg of ceftriaxone intravenously with fullresuscitation facilities available. He was commenced on TPHA = Treponema pallidum haemagglutination; FTA = fluorescent prednisolone 10 mg three times daily for 24 hours before treponemal antibody; RPR = rapid plasmin reagin; TPPA = Treponema and 48 hours after starting treatment because of the risk of a pallidum particle agglutination.
*In January 2000 the laboratory began monitoring TPPA instead of TPHA.
Jarisch-Herxheimer reaction causing neurological deteriora- may be easier to cure than disease of longer duration that Correspondence to: Dr S Shann, Department of Genitourinary could involve meninges and brain parenchyma.8 Medicine, Sunnybank Wing, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK; siobhan.mcmyler@leedsth.nhs.uk The patient in our case had evidence of both cerebrovas- cular and parenchymal disease. He received 14 days of Accepted for publication 27 February 2003 ceftriaxone (3 days intravenously and 11 days intramuscu-larly) and was followed up for 36 months with blood and CSFanalysis. His blood RPR fell from 1 in 128 pre-treatment to 1 in 16 (a threefold reduction) 36 months after treatment. His 1 Hahn RD, Webster B, Weickhardt G, et al. The results of treatment of 1086 CSF TPHA and FTA abs have remained detectable but the general paralytics the majority of whom were followed up for more than 5 RPR was negative on the last occasion. The protein level in the CSF has consistently declined from 2.03 g/l to 0.55 g/l as 2 Clinical Effectiveness Group. UK national guidelines on STIs and closely related conditions. Sex Transm Infect 1999;75(Supp l).
have the CSF albumin and IgG levels. The IgG index remains 3 Goh BT, Van Voorst Vader PC. European guideline for the management of elevated but the albumin quotient has normalised. Even after syphilis. Int J STD AIDS 2001;12(suppl 3):14–26.
successful treatment these latter two parameters may remain 4 Centers For Disease Control And Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002;51(RR-6):18–26.
5 Marra CM, Slatter V, Tartaglione TA, et al. Evaluation of aqueous penicillin G There are few other reports of successful treatment of and ceftriaxone for experimental neurosyphilis. (letter) J Infect Dis symptomatic neurosyphilis in HIV negative individuals with ceftriaxone. There is a single case of treatment of 6 Steele RW. Ceftriaxone therapy of meningitis and serious infections. Am J asymptomatic neurosyphilis9 and of treatment of meningo- 7 Dowell ME, Ross PG, Musher DM, et al. Response of latent syphilis or myelitis complicating secondary syphilis.10 Our case suggests neurosyphilis to ceftriaxone therapy in persons infected with human that ceftriaxone may be a useful alternative in HIV negative immunodeficiency virus. Am J Med 1992;93:481–8.
patients with neurosyphilis, but because of the doubt about 8 Marra CM, Boutin P, McArthur JC, et al. A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in its efficacy in those who are co-infected, a larger study with human immunodeficiency virus-infected individuals. Clin Infect Dis CSF levels of ceftriaxone should be performed.
9 Hook EW, Baker-Zander SA, Moskovitz BL, et al. Ceftriaxone therapy for . . . . . . . . . . . . . . . . . . . . .
asymptomatic neurosyphilis. Case report and Western blot analysis ofserum and cerebrospinal fluid IgG response to therapy. Sex Transm Dis S Shann, J Wilson, Department of Genitourinary Medicine, Leeds 10 Gentile JH, Viviani C, Sparo MD, et al. Syphilitic meningomyelitis treated General Infirmary, Great George Street, Leeds LS1 3EX, UK with ceftriaxone: case report. Clin Infect Dis 1998;26:528.

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