Correlation of Culture Positivity, PCR Positivity, and Burden of Borrelia burgdorferi Sensu Lato in Skin Samples of Erythema Migrans Patients with Clinical Findings

PLoS One. 2015 Sep 9;10(9):e0136600. doi: 10.1371/journal.pone.0136600. eCollection 2015.

Abstract

Background: Limited data are available regarding the relationship of Borrelia burden in skin of patients with erythema migrans (EM) and the disease course and post-treatment outcome.

Methods: We studied 121 adult patients with EM in whom skin biopsy specimens were cultured and analyzed by quantitative PCR for the presence of Borreliae. Evaluation of clinical and microbiological findings were conducted at the baseline visit, and 14 days, 2, 6, and 12 months after treatment with either amoxicillin or cefuroxime axetil.

Results: In 94/121 (77.7%) patients Borrelia was detected in skin samples by PCR testing and 65/118 (55.1%) patients had positive skin culture result (96.8% B. afzelii, 3.2% B. garinii). Borrelia culture and PCR results correlated significantly with the presence of central clearing and EM size, while Borrelia burden correlated significantly with central clearing, EM size, and presence of newly developed or worsened symptoms since EM onset, with no other known medical explanation (new or increased symptoms, NOIS). In addition, the logistic regression model for repeated measurements adjusted for time from inclusion, indicated higher Borrelia burden was a risk factor for incomplete response (defined as NOIS and/or persistence of EM beyond 14 days and/or occurrence of new objective signs of Lyme borreliosis). The estimated association between PCR positivity and unfavorable outcome was large but not statistically significant, while no corresponding relationship was observed for culture positivity.

Conclusions: Higher Borrelia burden in EM skin samples was associated with more frequent central clearing and larger EM lesions at presentation, and with a higher chance of incomplete response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Bacterial / blood
  • Biopsy
  • Borrelia burgdorferi / growth & development
  • Borrelia burgdorferi / immunology
  • Borrelia burgdorferi / isolation & purification*
  • Cefuroxime / analogs & derivatives
  • Cefuroxime / therapeutic use
  • Disease Progression
  • Erythema Chronicum Migrans / drug therapy
  • Erythema Chronicum Migrans / microbiology*
  • Erythema Chronicum Migrans / pathology
  • Female
  • Humans
  • Lyme Neuroborreliosis / epidemiology
  • Male
  • Middle Aged
  • RNA, Ribosomal, 16S / analysis
  • Real-Time Polymerase Chain Reaction
  • Ribotyping
  • Skin / microbiology*
  • Skin / pathology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • RNA, Ribosomal, 16S
  • Amoxicillin
  • Cefuroxime
  • cefuroxime axetil

Grants and funding

The microbiological analyses were funded by Baxter. The clinical part of the study was supported by the Slovenian Research Agency (grant number P3-0296). Baxter provided support in the form of salaries for authors MOR, AT and IL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.