There are a surprising number of drugs, many of which are not antibiotics, which have anti-lyme/anti-persister effects. An additional 113 agents are presented by Zhang in the latest article published in “antibiotics” September, 2015. Some of these drugs are in common use, amongst Lyme patients – but to treat something else. The list includes antibiotics, antivirals, antifungals, anthelminthics and antiparasitics. Other, unexpected agents are in the list include an arcane antidepressant. Of course daptomycin heads the list. Drugs already in common use include: artemisinin (very effective), Diflucan-fluconazole (very effective) and rifamycin related agents. The latter two from this list are referred to as active hits. Other less active hits include some quinolones (not in clinical use) and a limited list of cell wall agents, available, but also not generally used. Rifampin (rifamycin) is of greater interest to me. My grasp of this drug has evolved. ALS (Advanced Laboratory Services) adds rifampin to culture medium to cultivate Borrelia. This might lead one to conclude that rifampin does not kill Lyme. Studies show that Rifampin kills persister forms of Lyme, not spirochetes: makes sense. Lyme is rarely found in blood. The few free swimmers are referred to as planktonic. These are motile spirochete forms. Spirochete forms are not killed by Rifampin and therefore can be cultured in a medium containing rifampin. The antipersister properties of rifampin are well known for the treatment of tuberculosis which requires the use of 4 antibiotics over a period of many months.
A new study published in “Nature” Lehar et al, discuses a novel approach for the treatment of Staph aureus. The study states that Staph bacteria hide inside cells, a protected milieu. (Mouse model). Staph aureus survive within phagocytic macrophages (the cells which “eat” and eliminate offending pathogens). The S. aureus were found to spread via a Trojan horse mechanism, a mechanism also employed by Lyme. The most potent anti-Staph aureus, MRSA antibiotics, vancomycin and daptomycin were unable to eradicate intracellular MRSA staph. In the mouse, intracellular infection allowed widespread invasion into many organs, including the brain. Not good.
These researchers took a fresh approach to killing S. aureus. The idea was to clone antibodies against S. aueus, find the best antibody and link it to an antibiotic creating a new molecule, an “antibody-antibiotic conjugate.
The antibiotic chosen for the project was neither vancomycin nor daptomycin. The drug was from the rifamycin class of antibiotics. Compared with vancomycin and daptomycin the minimal inhibitory concentration of the rifampin-like drug, intracellular and extracellular, was infinitely (slight exaggeration) better than the other two drugs. The second best drug studied was a forth agent, linezolid by the way. The rifamycin class of antibiotics were praised for: high potency, unaltered bactericidal activity in low phagosomal pH and an ability to withstand intracellular insults.
This new “AAC” compound was more effective than all other agents and able to clear the S. aureus in the mouse, including organisms hiding inside the intracellular niche. This new class of drug will not be available for human use, if it pans out, for a good 10 years or more.
I will not say exactly how I treat patients (which varies quite a bit), but...
The news about rifampin and related drugs is good. Perhaps with antibodies already present in our system we can hope for a similar result. The new compound is made of a rifampin-liked drug linked to a specific antibody.
I have long thought that rifampin was essential for treating Bartonella. Maybe this is wrong. Maybe the extra Herx that occurs with the addition of Rifampin because is due to killing a variety of pathogens living within cells, perhaps including Lyme and Staph for all we know.
The paradigm of treating Lyme is expanding and becoming more complex. An understanding of the pharmacology of individual drugs, synergistic properties, tissue penetration and many other factors must be understood by an experienced clinician in the formulation of effective drug cocktails. Individual responses to drugs are quite variable. There is not a one size fits all approach that is consistently effective.