Treponema pallidum macrolide resistance in BC

Article (PDF Available)inCanadian Medical Association Journal 174(3):349 · February 2006with5 Reads
DOI: 10.1503/cmaj.1050256 · Source: PubMed
Treponema pallidum
macrolide resistance in BC
Since mid-1997 British Columbia has
experienced an outbreak of syphilis,
initially in heterosexuals and more re-
cently among men who have sex with
men (MSM). Starting in 1999, primarily
in patients presenting to the sexually
transmitted diseases clinic at the BC
Centre for Disease Control (BCCDC),
moist lesions of primary and secondary
syphilis were swabbed for polymerase
chain reaction (PCR) testing for
ponema pallidum
. The PCR method
used was polA gene amplification us-
ing a CDC protocol.
When the question of azithromycin
resistance arose in 2004, specimens
were examined retrospectively for the
mutation in the
T. pallidum
gene in collaboration with investigators
from the University of Washington.
From 2000–2003, 1 of 47 positive
PCRs showed resistance in a travel-
acquired heterosexual case. In 2004, 4
of 9 positive PCRs showed the resistant
gene, all in MSM.
The 23sRNA gene correlated with
clinical resistance to azithromycin in
Dublin and San Francisco.
All of the BC patients received peni-
cillin G benzathine or doxycycline;
therefore, treatment failure with
azithromycin was not tested.
Treatment of choice in BC for early
syphilis is one dose of penicillin G
benzathine (2.4 MU intramuscularly).
Oral doxycycline therapy (100 mg twice
daily for 2 weeks)
is a second-line
treatment, with oral azithromycin ther
apy (one 2-g dose) as a third-line treat-
ent, especially in noncompliant pa-
tients who refuse injections. This se-
quence is in compliance with the
Canadian and US STD treatment
In a recent study in Africa, a 2-g oral
dose of azithromycin was as effective as
a 2.4-MU intramuscular dose of peni-
cillin G benzathine.
However, in devel-
oped countries, because of resistance
trends, azithromycin should be re-
served as a third-line treatment for
early syphilis, and patients thus treated
should be followed closely, both sero-
logically and clinically.
Muhammad G. Morshed
Hugh D. Jones
BC Centre for Disease Control
University of British Columbia Centre
for Disease Control
Department of Pathology and
Laboratory Medicine
University of British Columbia
Vancouver, BC
1. Hsi L, Rodes B, Chen CY, et al. New tests for
syphilis: rational design of a PCR method for de-
tection of
Treponema pallidum
in clinical speci-
mens using unique regions of the DNA polymerase
I gene.
J Clin Microbiol
2. Lukehart SA, Godornes C, Molini MS, et al.
Macrolide resistance in
Treponema pallidum
in the
United States and Ireland.
N Engl J Med
3. Health Canada.
Canadian STD Guidelines
. 1998.
4. US Centers for Disease Control and Prevention.
Sexually transmitted diseases treatment guidelines
MMWR Recomm Rep
5. Riedner G, Rusizoka M, Todd J, et al. Single-dose
azithromycin versus penicillin G benzathine for
the treatment of early syphilis.
N Engl J Med
Competing interests: None declared.
Determining optimal
catheterization rates
In an article by Michelle Graham and
an attempt was made to
determine optimal catheterization rates
by detecting the population rate of car
diac catheterization beyond which the
yield of high-risk coronary artery dis-
ase does not rise. However, some is-
sues are not quite clear. First, the au-
thors did not explain why they expected
to identify such a phenomenon in
Canada, a country with medium
catheterization rates, when they did not
mention any plateau effect in countries
with higher catheterization rates.
Second, the authors suggest that the
highest regional average catheteriza-
tion rates for men (638 per 100 000
population) and women (314 per
100 000 population) are lower than op-
timal catheterization rates. However,
higher rates of catheterization have al-
ready been reached in several regions
considered in this study for men and
for women (Fig. 3 and Fig. 4 in the arti-
and there are reportedly no signs
of a plateau effect. It is not clear why
those higher values were not consid-
ered as the rates that are also lower
than optimal catheterization rates, be-
cause that would be in accordance with
the applied method of detecting an op-
timal rate of catheterization.
Milorad Letic
Department of Biophysics
University School of Medicine
Belgrade, Serbia
Graham MM, Ghali WA, Faris PD, et al. Population
rates of cardiac catheterization and yield of high-
risk coronary disease.
[The authors respond:]
We thank Milorad Letic for his interest
in our paper. We embarked upon this
research because the concept of a
plateau in detection of high-risk coro-
nary disease is only theoretical, and no
previous studies have determined
whether a plateau actually exists. We
chose to use regional catheterization
rates from Alberta because of the avail-
ability of rich population-based data to
perform this analysis. The highest re
gional average rates that were used in
CMAJ January 31, 2006 174(3) | 349
© 2006 CMA Media Inc. or its licensors
    • "Since 2004, data from 2 randomized controlled trials and a metaanalysis have supported previous findings [52] demonstrating excellent efficacy of azithromycin in treating early syphilis456. However, increasing detection of a 23S ribosomal RNA (rRNA) mutation associated with resistance to macrolides has been reported worldwide [8,111213 53]. Although there are no data to delineate what in proportion of persons with the mutation therapy actually fails, the association of this mutation with clinical failures in small studies545556 is concerning. "
    [Show abstract] [Hide abstract] ABSTRACT: There are several important unanswered key questions in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. A single dose of 2.4 million units of benzathine penicillin G remains the drug of choice for managing early syphilis. Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status. Although additional data on the efficacy of azithromycin in treating early syphilis have emerged, reported increases in the prevalence of a mutation associated with azithromycin resistance precludes a recommendation for its routine use. Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms. In those persons with early syphilis who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers 6-12 months after adequate therapy and those with late latent infection who do not achieve a similar decline within 12-24 months, CSF examination should be considered. Among HIV-infected persons, CSF examination among all those with asymptomatic late latent syphilis is not recommended owing to lack of evidence that demonstrates clinical benefit. HIV-infected persons with syphilis of any stages whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis. If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.
    Full-text · Article · Dec 2011
    • "Molecular Typing of Treponema pallidum www.plosntds.orgA single mutation conferring macrolide resistance of T. pallidum has been reported in the U.S. [12,383940, Dublin [38], Canada [18,33,41], Shanghai [17,42], and the Czech Republic [43,44]. However, resistance has not been found in some African countries (Madagascar, Tanzania, and Uganda)454647. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. Methodology/principal findings: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. Conclusions/significance: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.
    Full-text · Article · Nov 2011
    • "Although both azithromycin (Hook et al., 1999Hook et al., , 2002 Kiddugavu et al., 2005; Riedner et al., 2005) and spiramycin (Idsoe et al., 1972) were found to be effective in the treatment of early syphilis in humans, an increasing incidence of syphilis isolates resistant to azithromycin has been reported over the past few years (Lukehart et al., 2004; Marra et al., 2006; Mitchell et al., 2006; Morshed & Jones, 2006). The resistance to macrolides is believed to be a product of the frequent use of macrolide regimens for the treatment and prevention of a number of nonsyphilitic infections. "
    [Show abstract] [Hide abstract] ABSTRACT: We report an occurrence of treatment failure after oral spiramycin therapy in a man with secondary syphilis and a reported penicillin and tetracycline allergy. Molecular detection revealed treponemal DNA in the blood of the patient and sequencing of the 23S rDNA identified an A to G transition at the gene position corresponding to position 2059 in the Escherichia coli 23S rRNA gene. The occurrence of this novel 23S rDNA mutation was examined among 7 rabbit-propagated syphilitic strains of Treponema pallidum and among 22 syphilis patient isolates from the Czech Republic. The prevalence of A2058G and A2059G mutations among clinical specimens was 18.2 and 18.2 %, respectively.
    Full-text · Article · Jul 2009
Show more