The Infectious Disease Society of America (IDSA) has long insisted that a maximum antibiotic course of 21 days is sufficient to eradicate the Lyme bacterium, while the International Lyme and Associated Diseases Society (ILADS) recommends a longer course of therapy with duration dependent on response to treatment. [1]

So what treatment approach are physicians actually adopting in clinical practice? And how frequently are they prescribing extended or combination antibiotic therapy?

A study by Tseng and colleagues, published in Clinical Infectious Diseases, sought to answer these questions by examining insurance claims data. The authors found that the use of extended courses of antibiotics and multiple antibiotics in the treatment of Lyme disease has increased in recent years.

The study examined the incidence and patterns of prolonged antibiotic treatment among Lyme disease patients in the Northeastern United States. Researchers retrospectively analyzed health insurance claims from patients treated for Lyme disease in 14 high-prevalence states between 2010 and 2012. [2]

The states included Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, and Wisconsin.

Most Lyme disease studies restrict inclusion to patients who meet the Centers for Disease Control and Prevention (CDC) two-tier testing criteria. However, this diagnostic approach relies on both ELISA and Western blot tests, which have well-documented sensitivity limitations—particularly in early or clinically complex disease.

In fact, a study by Wormser and colleagues found that only one-third of well-characterized Lyme disease patients met the CDC’s two-tier diagnostic criteria. [3]

Because the Tseng study was not restricted by two-tier test positivity, it offers a more realistic view of how Lyme disease is treated in everyday clinical practice.

Extended antibiotic use in Lyme disease

According to the study, 18% of Lyme disease patients were treated for more than five weeks, which the authors defined as extended therapy. The average duration of antibiotic treatment was 86 days, with a range spanning from 35 to 404 days.

Nearly half of patients (48.8%) were prescribed more than two antibiotics. Doxycycline was the most commonly prescribed medication, used in 74.4% of patients. Azithromycin was prescribed in 11.5%, while amoxicillin and cefuroxime were also commonly used.

The study did not evaluate the use of additional antibiotics such as minocycline or tetracycline, which are often prescribed for other tick-borne infections.

Extended therapy frequently involved switching antibiotics or prescribing combinations. Researchers found that 43% of patients were switched from one antibiotic to another, while 18% received combination therapy.

Who prescribes extended therapy?

A small group of physicians accounted for a disproportionate share of extended antibiotic prescribing. Sixteen doctors (3%) treated more than 20% of patients receiving extended therapy.

However, the remaining 80% of extended-treatment patients were treated by 472 additional providers. These findings suggest that prolonged antibiotic prescribing is not confined to a small group of outlier clinicians.

Interestingly, prescribing patterns among the 16 highest-volume prescribers were not markedly different from their peers when it came to whether extended therapy was used. Differences emerged only in total antibiotic exposure days, refill frequency, and antibiotic combinations.

Unanswered questions

The authors did not address why 488 physicians prescribed antibiotic courses longer than the 21 days recommended by the 2006 IDSA guidelines. [1]

Nor did they discuss that some clinicians recommend extended antibiotic therapy for selected patients based on individualized risk–benefit analysis and shared medical decision-making.

The ILADS evidence-based guidelines emphasize that patients with persistent manifestations of Lyme disease are heterogeneous and require individualized assessment.

“The clinical population of patients with persistent manifestations of Lyme disease is heterogeneous; therefore, the risk–benefit assessment needs to be done on an individualized basis, taking into account disease severity, responsiveness to therapy, tolerance of side effects, and patient preferences.”

Clinical implications

Medical societies continue to debate optimal treatment duration. In the meantime, physicians must rely on clinical judgment when treating Lyme disease patients.

This study demonstrates that hundreds of clinicians are already prescribing extended or combination antibiotic therapy in real-world practice—suggesting a gap between formal guidelines and bedside decision-making. That gap is not just a clinical one—it reflects the broader ethical obligation to pursue meaningful care when standard protocols fall short, a principle I examine in the ethics of Lyme disease diagnosis and treatment.

Sources

1. Wormser GP, et al. Clin Infect Dis. 2006.
2. Tseng YJ, et al. Clin Infect Dis. 2015.
3. Molins CR, et al. Clin Infect Dis. 2015.
4. Cameron DJ, Johnson LB, Maloney EL. Expert Rev Anti Infect Ther. 2014.