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
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.