Piperacillin as a Targeted Lyme Disease Treatment

A new study published in Science Translational Medicine reveals that the antibiotic piperacillin may offer a safer and more targeted way to treat Lyme disease. Unlike doxycycline—the current first-line treatment—piperacillin works at much lower doses and avoids the broad-spectrum side effects that disrupt the gut microbiome or harm human cells.

Researchers screened nearly 500 FDA-approved drugs and found that piperacillin uniquely interferes with how Borrelia burgdorferi, the bacteria that cause Lyme disease, builds its cell wall.

In mice, piperacillin was just as effective as doxycycline but spared the microbiome and worked at a 100-fold lower dose.

This is especially important for individuals with autoimmune diseases or post-treatment Lyme symptoms, where antibiotic side effects can worsen underlying inflammation. While more research is needed in humans, this breakthrough suggests we may be closer to a precision therapy for Lyme disease, an infection increasingly recognized as a potential trigger or confounder in autoimmune conditions.

Citation

Gabby, M. E., et al. (2025). A high-resolution screen identifies a preexisting beta-lactam that specifically treats Lyme disease in mice. Science translational medicine, 17(795), eadr9091. https://doi.org/10.1126/scitranslmed.adr9091