Scientists may be closing in on two major advances in the fight against Lyme disease: an overlooked antibiotic that eliminates the infection at exceptionally low doses and new insights into why symptoms often persist long after treatment.
Unlike doxycycline, piperacillin targets the Lyme disease bacteria specifically, sparing the gut microbiome from the disruption that typically accompanies doxycycline use.
“What was remarkable to us was how well piperacillin worked at really low doses,” Brandon L. Jutras, a professor in the microbiology-immunology department at Northwestern University Feinberg School of Medicine and lead researcher, told The Epoch Times. “We don’t need to provide it at a concentration that could kill other microbes.”
A More Targeted Approach
Lyme disease is an infectious illness that is spread to people through the bites of infected black-legged ticks and can lead to neurological and heart complications if untreated.Piperacillin works by interfering with the unique way Borrelia burgdorferi, the bacterium responsible for Lyme disease, builds its cell walls—a process essential for bacterial survival.
Because of this targeted mechanism, researchers believe piperacillin will spare the gut microbiome, which is often disrupted by broader-spectrum antibiotics like doxycycline. However, whether this more targeted approach could help prevent PTLD wasn’t addressed in the study.
Jutras’s team screened nearly 500 FDA-approved drugs, tracking how each compound affected the bacterium’s ability to build its distinctive cell wall.
“We could literally watch what happened to the cell wall when we added antibiotics,” Jutras said. “Piperacillin disrupted that process in a way that was incredibly specific to Borrelia.”
Currently, piperacillin is used to treat pneumonia and urinary tract infections and is not approved for use against Lyme disease in humans.
Beyond treatment, the researchers also see promise in piperacillin as a potential preventive measure. The idea is that one dose, received right after a tick bite, could stop the infection before it starts.
Early diagnosis is challenging since small tick bites may often go unnoticed, early symptoms may not appear for days or weeks, and not all patients develop the telltale bull’s-eye rash.
Diagnostic tests often rely on antibodies that take time to form, resulting in false negatives during early infection.
“You get bit by a tick. You go to your doctor. Right now, they might tell you to wait for symptoms or a positive test result,” Jutras said. “But with piperacillin, the idea is that you could receive a single prophylactic dose. It wouldn’t harm your microbiome, and it might prevent illness altogether.”
Jutras noted that while the findings make piperacillin a promising option, it must first be tested and proven effective in human trials before physicians can prescribe it.
Some experts also caution that any antibiotic—even at low doses—can contribute to antibiotic resistance.
“If piperacillin is proven to be highly effective, then that is a no-brainer in favor of preventing this potentially debilitating medical condition,” he said, adding that piperacillin is only available in intravenous or intramuscular form, so it’s unlikely to be practical for widespread preventive use after a tick bite.
Side effects of doxycycline may include gastrointestinal discomfort, increased sensitivity to sunlight, and potential risks to bone and tooth development in children. It’s also avoided during pregnancy.
Why Lyme Symptoms Persist
Lyme disease is now the most common vector-borne disease in the United States, with the Centers for Disease Control and Prevention estimating that approximately 500,000 Americans are diagnosed and treated each year.Unlike most infections, where the concern is primarily the initial acute phase, a significant worry with Lyme disease is that even after treatment, some people develop chronic symptoms of fatigue, pain, and brain fog that don’t respond to further treatment.
There is currently no single approved treatment for PTLD. Management typically focuses on relieving symptoms such as fatigue, joint pain, and brain fog through a combination of supportive care, lifestyle changes, and in some cases, extended or repeated antibiotic courses.
Jutras and his team believe that lingering bacterial debris may trigger an immune response that mimics chronic illness, even when no live bacteria remain. These peptidoglycan fragments were found in the liver and joint fluid of patients with Lyme arthritis, where they continued to provoke an immune response.
Holistic Approaches for Prevention
To help reduce the risk of persistent symptoms, many doctors who specialize in Lyme treatment take a holistic approach to prevention and recovery.By lowering the number of lingering pathogens and supporting immune function, these strategies can help manage and even reduce the chances of developing PTLD.
Bell highlighted the importance of identifying co-infections, such as Bartonella, Babesia, Ehrlichia, Anaplasma, or Rocky Mountain spotted fever, as well as addressing mold exposure and mycotoxins. “If co-infections or mold toxins are present and go untreated, the patient will have a much more challenging time recovering from Lyme,” he said.
Once symptoms indicating an acute infection are gone, these two botanicals may be a superior choice to antibiotics for long-term maintenance therapy after infection, Bell said.
In addition to herbal treatments, lifestyle changes—such as prioritizing quality sleep, engaging in gentle movement like walking or yoga, and minimizing exposure to environmental toxins—are a key part of recovery.
Clean tick bites with soap and water, and remove any attached ticks by using tweezers to pull them upward—without twisting or crushing them.
- Bull’s-eye rash (erythema migrans)
- Fever, chills, or fatigue
- Muscle aches and joint pain
- Swollen lymph nodes
- Severe joint swelling or pain
- Drooping on one side of the face (facial palsy)
- Numbness or tingling
- Irregular heartbeat
- Cognitive issues, such as memory loss