More effective antibiotic found for Lyme disease

Lyme disease, which is transmitted when deer ticks feed on infected animals and then bite humans, impacts nearly half a million individuals in the US annually. A team led by Northwestern University has now found that piperacillin, an antibiotic in the same class as penicillin, effectively cures mice of Lyme disease at 100 times less than the effective dose of doxycycline, the current gold standard treatment. Their work has been published in the journal Science Translational Medicine.

Even in acute cases, Lyme can be devastating; but early treatment with antibiotics can prevent chronic symptoms like heart and neurological problems and arthritis from developing. Unfortunately, doxycycline and other generic antibiotics wreak havoc on the microbiome, killing beneficial bacteria in the gut and causing troubling side effects even as it kills the Borrelia bacteria that causes Lyme. In addition to its negative impact on the gut, doxycycline also fails to help 10–20% of individuals who take it, and it is not approved for use in young children — who are at the highest risk of tick bites, and therefore, of developing Lyme.

In comparison, piperacillin is given at such a low dose that it has virtually no impact on resident gut microbes. It could also be used for pre-emptive interventions, in which someone potentially exposed to Lyme (with a known deer tick bite) would receive a single-dose shot of the medication.

To reach the conclusion that piperacillin would be the most effective and targeted treatment, the team screened nearly 500 medicines in a drug library, using a molecular framework to understand potential interactions between antibiotics and the Borrelia bacteria. Once the group had a short list of potentials, they performed additional physiological, cellular and molecular tests to identify compounds that did not impact other bacteria. They found that piperacillin exclusively interfered with the unusual cell wall synthesis pattern common to Lyme bacteria, preventing the bacteria from growing or dividing and ultimately leading to its death.

Historically, piperacillin has been administered as part of a two-drug cocktail to treat severe strep infections because strep can break down beta-lactams (piperacillin’s class of antibiotics) unless accompanied by tazobactam, which is an inhibitor of the enzyme that inactivates piperacillin. Research leader Brandon L Jutras wondered if using the same two medications, rather than piperacillin alone, would be a more effective bacteria killer.

“Bacteria are clever,” Jutras said. “Strep and some other bacteria combat antibiotics by secreting beta-lactamases that inactivate piperacillin. We found the approach is totally irrelevant in the context of Lyme disease and another way that makes piperacillin more specific. Adding the beta-lactamase inhibitor doesn’t improve the therapy because Lyme Borrelia don’t produce beta-lactamase, but the cocktail does negatively impact the microbiome by becoming more broadly functional against beneficial residents.”

As climate change extends tick seasons, and Lyme becomes more prevalent, Jutras hopes his research will help with developing proactive strategies to diagnose and treat it.

“I think the future for Lyme disease patients is bright in that we are approaching an era of customised medicine, and we can potentially create a particular drug, or a combination, to treat Lyme disease when others fail,” he said. “The more we understand about the various strains and species of Lyme disease-causing Borrelia, the closer we get to a custom approach.”

Image credit: iStock.com/Tomasz Klejdysz