Clarithromycin Treatment Failure due to Macrolide Resistance in Treponema pallidum in a Patient with Primary Syphilis

Woznicová, Vladana; Matějková, Petra; Flasarová, Magdalena; Zákoucká, Hana; Valiiova, Z; Šmajs, David

doi:10.2340/00015555-0774

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…Another mutation (A2059G) leading to macrolide resistance was described recently (Matějková et al, 2009) and a similar frequency of both A2058G and A2059G were found in clinical samples isolated from syphilis patients in the Czech Republic (Woznicová et al, 2010; Flasarová et al, 2011). Both A2058G and A2059G mutations were found also in clinical samples isolated in the USA (Pillay et al, 2011).…”

Section: Genetic Differences Among T Pallidum Subspecies Pallidumsupporting

confidence: 69%

Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Šmajs

Norris

Weinstock³

2012

Infection, Genetics and Evolution

107

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Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, T. paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections.

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Section: Genetic Differences Among T Pallidum Subspecies Pallidumsupporting

confidence: 69%

Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Šmajs

Norris

Weinstock³

2012

Infection, Genetics and Evolution

107

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“…The A2058G mutation encodes resistance to azithromycin, clarithromycin, erythromycin, and roxithromycin but not resistance to spiramycin (30)(31)(32). In contrast, A2059G is likely associated with resistance to all commonly used macrolides, including spiramycin (10).…”

Section: Discussionmentioning

confidence: 99%

Molecular Typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased Prevalence of Identified Genotypes and of Isolates with Macrolide Resistance

et al. 2014

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“…A single mutation conferring macrolide resistance of T. pallidum has been reported in the U.S. [12], [38]–[40], 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) [45]–[47].…”

Section: Discussionmentioning

confidence: 99%

Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis

Peng

Wang

et al. 2011

PLoS Negl Trop Dis

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BackgroundSyphilis 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 FindingsTwo 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%, χ2 = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ2 = 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/SignificancePrimary 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.

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Clarithromycin Treatment Failure due to Macrolide Resistance in Treponema pallidum in a Patient with Primary Syphilis

Cited by 10 publications

References 12 publications

Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Molecular Typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased Prevalence of Identified Genotypes and of Isolates with Macrolide Resistance

Molecular Typing of Treponema pallidum: A Systematic Review and Meta-Analysis

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