A new study gives hope that an effective treatment for Lyme disease may be available in the future. The new treatment involves the drugs cefotaxime and azlocillin.
The new paper appears in the Nature journal Scientific Reports.
Bacteria belonging to the group Borrelia burgdorferi cause Lyme disease. Most people develop it after being bitten by a tick that carries the bacteria.
Approximately 60–80% of people with Lyme disease develop a circular red skin rash called erythema migrans around the infected tick bite, and some also develop flu-like symptoms.
Most people develop the rash within 4 weeks of being bitten, but it can appear up to 3 months afterward.
Doctors routinely treat Lyme disease using tetracycline antibiotics, but between 10–20% of people with the disease later develop symptoms of fatigue, pain in their muscles, joints or nerves, and cognitive impairment.
These symptoms can continue for months or even years after their initial infection.
Researchers have suggested that this may because of drug-tolerant ‘persisters,’ a group of bacterial cells that survive the initial dose of antibiotics.
“Some researchers think this may be due to drug-tolerant bacteria living in the body and continuing to cause disease,” Jayakumar Rajadas, Ph.D., assistant professor of medicine and director of the Biomaterials and Advanced Drug Delivery Laboratory at the Stanford School of Medicine in California.
“Others believe it’s an immune disorder caused by bacteria during the first exposure, which causes a perpetual inflammation condition. Whatever the cause, the pain for patients is still very real.”
Now, a team of researchers from Stanford University in the U.S. and Loyola College in India set out to investigate whether two different antibiotic drugs, cefotaxime and azlocillin, could prove more effective at killing B. burgdorferi in the early stages of the disease than the currently prescribed antibiotic doxycycline.
The study team first tested to see whether different doses of the drugs could kill drug-tolerant borrelia bacteria grown on laboratory plates better than a standard Lyme disease antibiotic (doxycycline).
They carried out each experiment three times in triplicate (nine times in total). The team tested the drugs on different ages of bacteria, colonies that were 3 days old and growing rapidly, and colonies that were 7–10 days old and had reached a growth plateau.
At high concentrations, both drugs could kill all the drug-resistant borrelia cells and outperformed the standard Lyme disease antibiotic. When the study team tested the drugs at lower doses, azlocillin outperformed the standard antibiotic and cefotaxime, which left 20% of the drug-resistant cells alive.
The researchers tested the drugs in a small number of laboratory-bred mice that they infected with the bacteria. They treated the mice at different stages of the disease at 7, 14, and 21 days after infection.
They gave each mouse a daily dose of either azlocillin, cefotaxime, or the standard treatment for Lyme disease for 5 days. They cultured the mouse organs and checked for live bacteria using microscopy and genetic testing 2 days after the last dose.
The researchers found that both the standard treatment and azlocillin completely cleared the infection in the early stages of the disease, while cefotaxime did not.
The study team found that after 2 weeks of infection, they detected bacterial DNA in three of the seven mice given the standard treatment and two of the eight mice given azlocillin.
After 3 weeks, they could not find any bacterial DNA in the mice given azlocillin, but one of the three mice given the standard treatment still had the bacteria.
“This compound is just amazing […] It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.”
– Jayakumar Rajadas
The researchers plan to test azlocillin in a clinical trial on humans. Although these preliminary results are promising, this was a small study carried out in laboratory-grown mice, so researchers may not see similar results in humans.
However, as the Food and Drug Administration (FDA) has already approved azlocillin, and it has a good safety profile, it does make a promising candidate for such a trial.
“We have been screening potential drugs for 6 years,” Venkata Raveendra Pothineni, Ph.D., the lead study author says.
“We’ve screened almost 8,000 chemical compounds. We have tested 50 molecules in the dish. The most effective and safest molecules were tested in animal models. […] Our main goal is to find the best compound for treating patients and stop this disease.”
The team has patented the compound for the treatment of Lyme disease and is working with a company to develop an oral form of the drug.