Monday, June 11, 2018
I want to discuss several factors to be considered when choosing antibiotics in the management of Lyme disease.
There is a lot of confusion about the basic biology of the Lyme spirochete, Borrelia burgdorferi. A lot has been worked out but there is some confusion and misinformation on the internet.
Lyme is primarily an extracellular bacterium and resides in spaces between the cells, extracellular matrix. Without question Lyme spirochetes are occasionally intracellular but this is not the pathogen’s primary modus operandi. Not primarily intracellular.
Lyme is pleomorphic – takes on various forms and has modes of persisting. It forms round forms sometimes called cysts and congregates within biofilms. Does not form L-forms. Discussed elsewhere.
There are many classes of antibiotics. Antibiotics within a class share features, typically chemical structure and mode of action. I will mention a few examples.
The macrolide story is interesting. Zithromax and Biaxin are the two clinical agents of this class most used. On the face they sound similar. Both work by an intracellular mechanism inhibiting protein synthesis. But clinically there are differences. Biaxin is more effective against Lyme and Zithromax is more effective against other organisms, for example Babesia.
Zithromax has a unique and well-known ability to concentrate inside cells many times the concentration in serum. Because Lyme is primarily extracellular this quality is not a critical factor. Otherwise Zithromax would be much more effective than Biaxin.
When evaluating the effectiveness of an antibiotic against a particular bacterium, test tube, in-vitro data is cited. Numbers include: MIC (minimal inhibitor concentration), MBC (minimal bactericidal concentration). The time during which the antibiotic concentration exceeds the minimum kill level is called AUC, area under curve. These numbers estimate what may happen in humans taking the drugs. The numbers have limitations and can mislead.
Doxycycline is a favorite drug. It is extremely bioavailable and easily reaches a steady state in the blood stream. For this reason, many experts claim there is no reason to ever give the drug IV. Not true. There is evidence that tissue levels are much higher when the drug is given IV. Our target is tissues where the germ resides – not the blood.
Antibiotics may be: bactericidal, kill the bacteria or bacteriostatic stop their growth. In clinical practice there is no difference.
Antibiotics may interact with bacteria in diverse ways. In most cases a sustained blood level is preferred, example, B lactam drugs, amoxicillin and Ceftin. In other cases, drugs are more effective when there is a distinct peak serum level, as in the case with gentamicin, used for Bartonella.
Lyme has persister forms and is difficult to eradicate at best. Strategies to eliminate persister forms have including antibiotic cocktails and pulsing. Doctors have various theories and preferences.
Questions to consider when choosing an antibiotic:
1) What germ(s) are we targeting? What is the pathobiology of the germ? Big word. How does the pathogen make us sick? Where does the target germ reside?
2) Does the antibiotic reach the target(s)?
3) Is the antibiotic bioavailable (get into blood stream)?
4) Does the antibiotic offer the right “killing kinetics?” This asks if there is a steady state versus a sharp peak and trough levels, as desired, based on the pharmacology of the antibiotic.
5) Oral or intravenous therapy?
6) Continuous or pulse therapy?
7) Single therapy or combination therapy and how to proceed?
There are many other factors and considerations. For example, when used in combination antibiotics may exhibit synergy, mechanism unknown. Drug combinations may be toxic or cancel out the efficacy of the other. For example, rifampin reduces the effective dose of Mepron by 50%.
Figuring out how best to treat infections is complicated. Standard therapies may be poorly explained and not be effective. We may have to go a step or 10 further. But there should be a method to the madness.
Daniel A Jaller, MD focuses on Lyme disease and related illnesses at his clinical practice, Paradigm Medicine. He accepts new patients by appointment: 301 528 7111. He does not participate with any insurance plans.