Monday, March 18, 2013

Blood brain barrier

A lot of patients are concerned about the blood brain barrier (BBB). They want to know which antibiotics pass through it and/or if only intravenous antibiotics are able to traverse it.

Well then, what is the BBB? It is a diffusion barrier created by special features of small blood vessels leading to the brain. The lining of these vessels, the endothelium, contains unique cellular elements. Tight junctions in the endothelium (inside walls of blood vessels) are made up of a number of factors including "astrocyte end-feet." Astrocytes are supporting cells found in the brain. Most importantly, the BBB keeps out most blood borne substances including antibodies. Antibiotics that cross the BBB tend to have certain physical characteristics including: small molecular size, being lipophilic, binding to fatty molecules on cell membranes, low plasma protein binding and other specialized characteristics.

One of the best drugs is the original, used to syphilis, penicillin. Penicillin derivatives like amoxicillin are also effective. Cephalosporins do not do as good a job; there is some penetration. Then for brain penetration amoxicillin is a better choice than the popular Ceftin and Omnicef. Quinolones do an excellent job crossing the BBB (Levaquin, Cipro and others). Tetracylines are at the top of the list, especially doxycycline. Macrolides, (Biaxin, Zithromax) do a poor job because of their size. Flagyl and Tindamax,which are small and lipophilic, do a great job of passing through the BBB.  Rifamycins (Rifampin) are large and penetrates poorly into the brain. Sulfonomides and Trimethoprim, the ingredients in Bactrim, fulfil the right criteria and pass well through the BBB. This is by no means a comprehensive list of all antibiotics which has been used for Lyme disease.

I haven't talked about Rocephin, our favorite intravenous Lyme drug. It is a cephalosporin. Above I state above this class of drugs generally has poor penetration into the brain. Apparently some cephalosporins penetrate better than others. Literature about Rocephin is mixed;  but contrary to many claims, it does pass the blood brain barrier. Let me mention that Rocephin is used a lot for meningitis. In typical meningitis with active inflammation, there is a breakdown of the BBB and most antibiotics penetrate. With typical chronic Lyme, neuroborreliosis patients, there is no active inflammation. High doses of the drug, with high serum levels obviates the BBB problem. Rocephin is generally tolerated at high doses. Rocephin has other favorable properties: the long half life with once daily dosing,  makes it easy to use this effective intravenous therapy at home. Even though some oral medications have better penetration through the BBB:  the IV route makes Rocephin work better.

Quinolones are the only class of antibiotics I am familiar with when given orally achieve serum concentrations which approach those of IV infusion.

The susceptibility of the organisms to the drug being used is the most important factor.

In reading about the BBB it is fascinating to learn that many other brain diseases may be due to defects in the integrity of the BBB. For example autoimmune brain diseases like MS only occur when antibodies pass through the brain's shield. The same may be true for Alzheimer's disease and other neuro-degenerative diseases which could be characterized primarily, as disorders of the blood brain barrier.

One last point: in general, large bacteria cannot pass through the BBB;  but thin, slippery Borrelia spirochetes, including of course, Borrelia burdorferi, drill through the gauntlet with ease. The brain is a safe haven for Lyme but very few other bacteria are able to get in. But it seems that intraerythrocytic germs like Bartonella and Babesia might hitch-hike in on the backs of red blood cells.