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; email@example.com
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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