Review of Current Evidence and Comparison of Guidelines for ...

EUR/03/5045931
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United Kingdom guidelines recommend benzyl penicillin as an alternative treatment and also
sanction the use of oral amoxycillin with probenecid. These regimes are for 17 days.
Amoxycillin/probenecid regimes have been reported to achieve treponemicidal levels in CSF in
two small studies (7 and 17 patients, but these did not report clinical outcomes (65,77). European
guidelines recommend benzyl penicillin as first line, with PBP as second line treatment.
The use of steroids is recommended in the United Kingdom and European guidelines for
consideration in all patients with neurosyphilis, but not mentioned in the CDC guidelines. In the
Russian Federation guidelines it is recommended for patients with psychotic symptoms, cerebral
or spinal cord gummata. It is believed that this may limit the Jarisch-Herxheimer reaction;
however; there is no evidence of prevention of the reaction in patients given steroids with
treatment for Borrelia (which also causes this reaction).
Alternatives are limited, with European and United Kingdom citing doxycycline as the drug of
choice (200 mg bd po for 28 days), despite limited data. Whiteside and colleagues studied five
patients who achieved adequate CSF levels with 200 mg bd of doxycycline (78). The CDC
favours ceftriaxone, or penicillin desensitisation. There is minimal clinical data supporting
ceftriaxone, although there is some biological evidence for its use. Two small studies have
suggested that ceftriaxone is efficacious in treating HIV positive patients with neurosyphilis
(79,83).The trials are summarized in Table 7 (79–83).
Neurosyphilis in Russian Federation is also treated with benzyl penicillin or PBP, used in the
same way as the United Kingdom, CDC guidelines. However amoxycillin/probenecid treatment
is avoided. Ceftriaxone is used as an alternative in penicillin allergy. There has been a Russian
review written on efficacy of treatment of neurosyphilis, covering a wide range of different
treatments including ceftriaxone and a small number of patients, but this review does not add any
information on comparative regimes (6) (see Annex 5).
HIV Infection
The advent of HIV infection has led to considerable debate about the effectiveness and
appropriateness of the regimes used for treating all stages of syphilis (86–97). The controversy
was catalysed by a number of case reports on failure of syphilis treatment in patients with HIV,
and on increased severity of infections in HIV positive patients (84,85,28–34). As HIV is a new
infection there is difficulty in assessing this data objectively due to a significant potential
reporting bias. In his article Musher reviews the evidence for both an accelerated course of
syphilis infections in HIV positive patients, and for a higher rate of syphilis treatment failure
(66).
Other trials specifically addressing treatment in HIV infection are reviewed by Augenbraun and
Rolfs (18). These include a study by Goeman et al. with 193 sex workers in Zaire (98). The
patients were treated with CDC standard therapy (BBP three doses). Serological response rates
were similar in HIV positive and negative patients, with no clinical relapse. However, this was a
cohort study with large loss to follow up, HIV seroconversion during follow up in some patients,
and no stage of syphilis was noted (likely late latent disease). Schofer et al. retrospectively
studied 100 HIV positive patients treated for late latent or neurosyphilis as per CDC guidelines,
which showed multiple relapses for neurosyphilis (99). However in the study by Rolfs and
colleagues discussed earlier (21) the absence of evidence of undesired clinical sequelae or
clinical treatment failure in the HIV positive group has helped to allay fears about whether