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Intravenous Antibiotic Therapy and Associated Diagnostic Testing for Lyme Disease

Lyme Disease
Treatment of Lyme disease consists of oral antibiotics, except for the following indications.


A 2- to 4-week course of intravenous (IV) antibiotic therapy may be considered medically necessary in individuals with neuroborreliosis with objective neurologic complications of documented Lyme disease (see the following for methods of documentation).

Objective neurologic findings include:

Lymphocytic meningitis with documented cerebrospinal fluid (CSF) abnormalities

Cranial neuropathy, other than uncomplicated cranial nerve palsy, with documented CSF abnormalities

Encephalitis or encephalomyelitis with documented CSF abnormalities



Lyme disease may be documented by serologic testing or by clinical findings of erythema migrans in early infection. Documentation of CSF abnormalities is required for suspected central nervous system infection, as indicated above.

Serologic documentation of infection requires:

Positive or indeterminate enzyme-linked immunosorbent assay, AND

Positive immunoblot blot by Centers for Disease Control and Prevention criteria.

Documented CSF abnormalities include ALL of the following:


Evidence of intrathecal production of Borrelia burgdorferi antibodies in CSF; and

Increased protein levels.

Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi in CSF samples may be considered medically necessary and may replace serologic documentation of infection in individuals with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies. Lyme Carditis A single 2- to 4-week course of IV antibiotics may be considered medically necessary in individuals with Lyme carditis, as evidenced by positive serologic findings (defined above) and associated with high degree atrioventricular block or a PR interval more than 0.3 seconds. Documentation of Lyme carditis may include PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal. Lyme Arthritis A single 2- to 4-week course of IV antibiotic therapy may be considered medically necessary in the small subset of individuals with well-documented Lyme arthritis who have such severe arthritis that it requires the rapid response associated with IV antibiotics. Documentation of Lyme arthritis may include PCR-based direct detection of B. burgdorferi in the synovial tissue or fluid when results of serologic studies are equivocal. Antibiotic Therapy Intravenous antibiotic therapy is considered investigational in the following situations: Individuals with symptoms consistent with chronic fatigue syndrome or fibromyalgia, in the absence of objective clinical or laboratory evidence of Lyme disease; Individuals with seronegative Lyme disease in the absence of CSF antibodies; Initial therapy in individuals with Lyme arthritis without coexisting neurologic symptoms; Cranial nerve palsy (eg, Bell palsy) without clinical evidence of meningitis; Post-antibiotic Lyme arthritis (unresponsive to 2 courses of oral antibiotics or to 1 course of oral and 1 course of IV antibiotic therapy); Individuals with vague systemic symptoms without supporting serologic or CSF studies; Individuals with a positive enzyme-linked immunosorbent assay test, unconfirmed by an immunoblot or Western blot test (see definition above); Individuals with an isolated positive serologic test in the setting of multiple negative serologic studies; Individuals with chronic (≥6 months) subjective symptoms (“post-Lyme syndrome”) after receiving recommended treatment regimens for documented Lyme disease. Repeat or prolonged courses (eg, >4 weeks) of IV antibiotic therapy are considered investigational.

Diagnostic Testing

Repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations:

as a justification for the continuation of IV antibiotics beyond 1 month in individuals with persistent symptoms

as a technique to follow therapeutic response.

PCR-based direct detection of B. burgdorferi in urine samples is considered investigational in all clinical situations.

Genotyping or phenotyping of B. burgdorferi is considered investigational.

Other diagnostic testing is considered investigational including but not limited to “stand-alone” C6 peptide enzyme-linked immunosorbent assay, determination of levels of the B-lymphocyte chemoattractant CXCL13, or Outer surface protein A (OspA) antigen testing for diagnosis or monitoring treatment.

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