Superior Efficacy of Combination Antibiotic Therapy versus Monotherapy in a Mouse Model of Lyme Disease

Abstract

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by Borrelia burgdorferi (Bb) which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics. However, 10-20% of patients experience chronic symptoms because of delayed or incomplete treatment, a condition called Post-Treatment Lyme Disease (PTLD). Some Bb persists in PTLD patients after the initial course of antibiotics and an effective treatment to eradicate the persistent Bb is needed. Other organisms that cause persistent infections, such as M. tuberculosis, are cleared using a combination of therapies rather than monotherapy. A group of Food and Drug Administration (FDA)-approved drugs efficacious against Bb were used in monotherapy or in combination in mice infected with Bb. Different methods of detection were used to assess the efficacy of the treatments in the infected mice including culture, xenodiagnosis, and molecular techniques. None of the monotherapies eradicated persistent Bb. However, 4 dual combinations (doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime) and 3 triple combinations (doxycycline + ceftriaxone+ carbomycin, doxycycline + cefotaxime+ loratadine, dapsone+ rifampicin+ clofazimine) eradicated persistent Bb infections. These results suggest that combination therapy should be investigated in preclinical studies for treating human Lyme disease.

Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections

“…The study by Sapi et al confirmed the culture findings found by Feng et al at Johns Hopkins University on the superior efficacy of dapsone against Borrelia persisters using multiple antibiotic combinations [ 108 ]. To date, there has been one animal study by Embers et al (pre-print) proving dapsone’s efficacy in Lyme disease in a mouse model [ 237 ], which confirmed the superior efficacy of combination antibiotic therapy vs. monotherapy in the treatment of borreliosis. The findings of that study were that “none of the monotherapies eradicated persistent Bb; however, 4 dual combinations, including dapsone + rifampicin, dapsone + clofazimine, and 3 triple combinations (including dapsone + rifampicin + clofazimine), eradicated persistent Bb infections” [ 237 ].…”