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Metronidazole (Flagyl) is commonly used in select patients with treatment resistant, chronic Lyme. When present in a hostile environment, such as growth medium lacking some nutrients, or spinal fluid, or serum with certain antibiotics added, Bb will change into a cystic form. This cyst seems to be able to remain dormant, but when placed into an environment more favorable to its growth, the cyst can open, and an intact spirochete emerges. The conventional antibiotics used for Lyme, such as the penicillins, cephalosporins, etc. do not kill the cystic form of Bb. Furthermore, the cyst lacks the usual surface antigens found on the spirochete (these are the markers detected by ELISAs and western blots). This may be another reason for the chronically sick Lyme patient remaining seronegative.

There is evidence that metronidazole will kill the cystic form. This fits with the now well known clinical observations that metronidazole can be remarkably effective for many chronic Lyme patients. However, this medication apparently has no effect on intact spirochetes. Therefore, the trend now is to treat the chronically infected patient who has resistant disease by combining metronidazole with one or two other antibiotics to target all forms of Bb. Because there is laboratory evidence that tetracyclines may inhibit the effect of metronidazole, this class of medication may not be as useful as others in these two- and three-drug regimens. There have been some recent reports that Bb does not contain genes that would confer susceptibility to metronidazole. However, this clearly does not fit with in vitro and a large body of clinical data, which have demonstrated the usefulness of this agent in the Lyme patient. Perhaps we do not have all the genetic information needed to dismiss the use of this agent. Once again, real world experience is one step ahead of bench research.

Important precautions:

Pregnancy while on metronidazole is not advised, as there is a risk of birth defects.
No alcohol consumption! A severe, “antabuse” reaction will occur, consisting of severe nausea, flushing, headache, and other unpleasant symptoms.
Metronidazole is potentially neurotoxic. Peripheral neuropathy may result. Therefore, breaks in treatment are commonly prescribed, such as using this agent every other week.
Yeast overgrowth is especially common. A strict anti-yeast regimen must be followed.
VERY severe Herxheimer-like reactions are seen in the more ill patient during the first week of therapy, and again four weeks later.

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