Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.
Conclusions
Neuroborreliosis (Adult and Pediatric)
Based on four Class II studies antibiotic regimens have been established as probably safe and effective for both children and adults. One Class I and one Class II study suggest that parenteral regimens are probably safe and effective for severe neurologic disease but two Class II studies and numerous Class III and IV studies suggest that oral treatment, particularly with doxycycline, is comparably safe and effective in many situations not involving parenchymal central nervous system (CNS) involvement. Although the evidence is stronger in adults than children, all available evidence indicates that the responses to oral treatment are comparable in adults and children. However, it must be emphasized that no definitive data exist to establish the superiority—or lack thereof—of either oral or parenteral treatment. Specific regimens are listed in tables 1 and 2 in the original guideline document.
Post-Lyme Syndrome
Several Class I studies indicate that the disorder referred to as post-Lyme syndrome does not respond to prolonged courses of antibiotics and that such treatment can be associated with serious adverse events (see "Potential Harms" field).
Recommendations
- Parenteral penicillin, ceftriaxone, and cefotaxime are probably safe and effective treatments for peripheral nervous system Lyme disease and for CNS Lyme disease with or without parenchymal involvement (Level B recommendation).
- Oral doxycycline is probably a safe and effective treatment for peripheral nervous system Lyme disease and for CNS Lyme disease without parenchymal involvement (Level B recommendation). Amoxicillin and cefuroxime axetil may provide alternatives but supporting data are lacking.
- Prolonged courses of antibiotics do not improve the outcome of post-Lyme syndrome, are potentially associated with adverse events, and are therefore not recommended (Level A recommendation).
Definitions:
Classification of Recommendations
A = Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)
B = Probably effective, ineffective, or harmful for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.)
C = Possibly effective, ineffective, or harmful for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
U = Data inadequate or conflicting; given current knowledge, treatment is unproven.
Classification of Evidence for Therapeutic Intervention
Class I: Prospective, randomized, controlled clinical trial (RCT) with masked outcome assessment, in a representative population. The following are required:
- Primary outcome(s) clearly defined
- Exclusion/inclusion criteria clearly defined
- Adequate accounting for drop-outs and cross-overs with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a–d above OR an RCT in a representative population that lacks one criterion a–d.
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome is independently assessed, or independently derived by objective outcome measurement.*
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.
*Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer's (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data)