Researchers at Tulane University have found certain combinations of antibiotics to be more effective in treating Lyme disease than the standard prescribed course of single antibiotics.

These findings, published in Frontiers in Microbiology, clearly indicate the need for improved Lyme disease treatments for patients with persistent symptoms, particularly those who have not responded to standard antibiotic treatment.

Unfortunately, many Lyme-infected patients do not receive a proper diagnosis until months after the tick bite, allowing the infection to disseminate throughout their body. Animal studies have shown that disseminated Borrelia is harder to eradicate, leading to persistent infection.

Prior research has shown that monotherapy with doxycycline or ceftriaxone are not effective in clearing persistent Lyme disease. The concept of combination therapy is already well-established for other persistent infections, such as tuberculosis.

Mono vs. combo

For this study, Tulane University’s Monica Embers, PhD, and colleagues conducted a series of detailed experiments using a single antibiotic (monotherapy) or a combination of antibiotics in mice infected with Borrelia burgdorferi (Bb).

They infected mice with Borrelia burgdorferi (strain B31) via needle inoculation and allowed the disease to disseminate for two months without treatment. During that time, Bb infection was confirmed with ear biopsies and blood tests.

Two months after infection, the  mice were administered either a single antibiotic or a combination therapy for 28 days.

Then, two months after receiving antibiotics, the mice were subjected to a xenodiagnosis technique where clean ticks fed on the mice for three to six days. The ticks were then removed and subsequently tested for the presence of Bb.

At the end of the experiment (5-6 months post infection), multiple tissues from the mice were subjected to two different cultures, and several molecular detection techniques including 16s PCR which detects DNA, and RT-PCR which detects RNA.

The results of those tests are demonstrated below based upon whether the mice received monotherapy (Table 1) or combination therapy (Table 2).

Table 1 clearly demonstrates that none of the single drugs eradicated the disseminated Bb, leaving the majority of mice with persistent infection.

Table 1

Eleven additional groups of mice were administered various combinations of drugs detailed in Table 2.

This research demonstrates the effectiveness of combination therapy for disseminated Bb. Table 2 shows that in 8 out of 11 groups of mice, two or more months after receiving a combination of antibiotics, there were no (0/5) positive spirochetes in culture.

For 7 out of the 11 combination therapy groups, viable spirochetes were also not detectable by xenodiagnosis culture of the tick’s midgut or the presence of Bb RNA inside the tick.

The mouse groups that remained positive for Bb infection were given azlocillin+ Bactrim (100%), disulfiram+ Bactrim (100%), and disulfiram + azlocillin (80%).

Table 2

Future clinical trials in humans

The researchers propose that the combination of ceftriaxone + doxycycline may be a good candidate for future clinical trials in humans. This combination therapy performed well and both drugs are well tolerated and have good safety profiles. Cefotaxime + doxycycline was also effective at eradicating Bb infection and should be considered for further research.

The authors also propose further research into dapsone combinations. They state, “Dapsone in dual or triple combinations with rifampicin, clofazimine, or rifampicin + clofazimine were also effective at eradicating viable Bb. The combinations of dapsone with rifampicin, clofazimine or both are already the therapies of choice to treat multidrug-resistant M. tuberculosis or leprosy (dapsone)…”  Previous clinical studies have demonstrated efficacy of an eight-week dapsone combination therapy in Lyme disease patients with persistent symptoms.

In this experiment, not one of the single antibiotics eradicated the persistent infection after a 28-day treatment course. However, several combination therapies of already FDA-approved drugs, were successful in clearing the infection in mice.

However, in an age of growing antibiotic resistance, many Lyme-treating physicians have learned to use botanical medicines to boost the efficacy of antibiotics. Definitely something that warrants further research.

This study suggests a significant need for further clinical studies of combination antibiotic therapies, using drugs that are already FDA-approved, in treating persistent Lyme disease in humans.

Click here for Dr. Ember’s new online course, “Combination Antibiotic Therapy for Treatment of Lyme Disease.” This free course is designed for medical professionals seeking to deepen their understanding of Lyme disease treatment. It is also available to the public.

LymeSci is written by Lonnie Marcum, a physical therapist and mother of a daughter with Lyme. She served two terms on a subcommittee of the federal Tick-Borne Disease Working Group. Follow her on Twitter: @LonnieRhea  Email her at: lmarcum@lymedisease.org.

Reference

Alruwaili Y, Jacobs MB, Hasenkampf NR, Tardo AC, McDaniel CE, Embers ME. Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease. Front Microbiol. 2023 Nov 21;14:1293300. doi: 10.3389/fmicb.2023.1293300. PMID: 38075920; PMCID: PMC10703379.