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Monday, November 18, 2019

Disulfiram resistant strains of Lyme!

No. I don't know if there are disulfiram resistant strains of Lyme. However, the emergence of such strains seems inevitable but may be preventable.

How does disulfiram kill bacteria?  Biochemistry.  Disulfides or thiols bind to critical metabolites in the bacteria. Medical literature claims it has a narrow spectrum of action killing specific gram-positive organisms, like Staph aureus and several others. The construction of the cell wall of susceptible bacteria determines the entre of the drug.  Spirochetes like Borrelia burgdorferi, are neither gram positive nor negative. The out surface of the spirochete is comprised of double membrane, one that is lipophilic (loves fat). The disulfiram molecule is also lipophilic (loves fat). This shared biochemistry dooms the Lyme spirochetes.  The disulfiram molecule carrying its poisonous chemicals is a trojan horse and quickly puts the spirochetes out of commission.

A narrow spectrum may be a good thing. This is the ideal scenario. The drug kills the target and only a few bystanders (collateral damage). Most antibiotics essentially nuke, or carpet bomb our bodies, carrying around their 2-8 pounds of normal flora – bacteria, indiscriminately killing huge numbers of good guys.

Disulfiram represents an entirely new class of antibiotic with a novel way of killing bacteria.

Traditional antibiotics work by inhibiting cell wall synthesis, inhibiting protein synthesis by disrupting ribosomes, interfering with DNA or RNA function – and that’s about it.

We don’t know if antibiotic resistance will emerge against disulfiram. The best predictor of what might happen is history.

There currently exist bacteria resistant to antibiotics from each of the known classes.

It may be wise to listen to Alexander Fleming, the Nobel laureate who discovered Penicillin. Over the course of his career he watched susceptible strains of Staphylococcus become resistant to the the wonder drug, penicillin, in a few short years.

He cautioned that one must make sure the antibiotic is necessary, then make sure the dose is high enough and the drug is given long enough to prevent the emergence of resistant strains of bacteria.

Popular pulsing and prescription of low, subtherapeutic doses of antibiotics/disulfiram are practices which needed to be avoided lest we kill the goose who lays the golden eggs

The emergence of resistance is nearly universal.  It has happened with every bad infectious disease you can think of, ranging from malaria and tuberculosis to HIV. It is the rule, not the exception.

The Lyme buggers are very, very smart. Expect no less.

ID doctors and the IDSA frequently talk about stewardship of antibiotics. I think they are frequently wrong about the details, but the concept is sound.

The thousands of patients suddenly taking disulfiram are a Facebook ragtag army with no sense of the history of antibiotics and germs and the decades long battles, lost and won.

My suggestion is simple but probably hard to implement.

Hit Lyme hard and long (disulfiram, and as I think about, a cocktail of other antibiotics makes a lot of sense). Treat for months after the disappearance of symptoms.

Using disulfiram as monotherapy, the only drug, may accelerate the evolution of disulfiram resistant Lyme strains.

In the words of the immortal Bob Marley “you have to kill it before it grows.”


lymie said...

If you have to start low and slow and can't tolerate larger doses of disulfiram, it is hard to see how resistance can be avoided. This drug has unpleasant side effects and it seems you would want to avoid those as much as possible.

bluesdoc said...

Yes, for those of us who cannot tolerate large and frequent doses (lord knows I've tried) perhaps the extremely long half life (hopefully of some of the active metabolites) will lessen the tendency to resistance. Sort of analogous to IM PCN - very low doses but persistent levels can be very effective for some.
jon sterngold md facep

Christian said...

I can already hear all the ID's go: "But disulfiram is not an antibiotic". It will not work.
Most MD's I have met have an extremely narrow view of just about anything regarding chemistry or medicine. To me, their view looks like viewing the world through a straw.
A lot of them can't cope with the concept that almost any small molecule will likely have antibiotic effects. Especially small ones, like disulfiram.

Susan said...
This comment has been removed by the author.
taran z said...

I thought it had been shown that borrelia doesn't develop antibiotic resistance per se, but rather produces persister forms that evade being killed by antibiotics and/or being controlled by the host's immune system.