Patient compliance with systemic antibiotics

The last RDH Under One Roof meeting was in Las Vegas. Good thing there wasn't a game that took bets on a patient's antibiotic compliance.

by Bill Landers

The last RDH Under One Roof meeting was in Las Vegas. Good thing there wasn't a game that took bets on a patient's antibiotic compliance. You'd have to be a fool to play it. In casino parlance, it's a sucker's bet. In fact, your chances of winning with a typical TID prescription would only be about 1 in 10! You'd have a far better chance of winning at the craps table where the odds are 1 in 5 of winning on the first roll. Even assuming that the doctor has prescribed the right antibiotic, the chance of patient compliance is a bigger gamble than shooting dice!

Why are the odds so stacked against it?

To really understand why, you need to know two things about antibiotics:

  1. Systemic antibiotics don't kill on contact. They kill very slowly, which is why they have to be taken so long.
  2. They don't work at all if the blood concentration drops below the Minimum Inhibitory Concentration (MIC), which isn't very long because the kidneys are constantly removing it. The antibiotic has to be constantly replenished, which is why it has to be taken so often.

Let's use metronidazole as an example. It's a very specific drug for gram-negative anaerobes. Surprisingly, metronidazole isn't bactericidal at all when it's in the bloodstream. Also, it can't enter our own (somatic) cells; the cell walls are too thick. Bacteria, though, hardly even have a cell wall, just a thin membrane. Even when it gets inside a bacterium, it's harmless … unless it's an anaerobic bacterium. Anaerobes have an enzyme that breaks metronidazole down. One of the resulting fragments reacts with the anaerobe's DNA, uncoiling it and breaking its strands. That, in turn, prevents the bacterium from synthesizing nucleic acids and making proteins. Eventually, the bacterium dies.

Here's the catch. The concentration of metronidazole has to be at least 10 micrograms per liter (the MIC value). Any less and the bacteria will reproduce faster than they die. The first dose takes about one to two hours to get through the digestive system and into the blood. But the initial concentration keeps falling because the kidneys are constantly filtering it from the blood; it gets excreted. If it isn't replenished every eight hours (for 250 mg tablets), the serum concentration drops below the MIC and no longer inhibits growth ... and grow those bacteria can! On average, periodontal microbes double their numbers every four-and-a-half hours. Miss a single dose and every two bacteria become eight.

Whether a drug works or not depends on three factors:

  1. Drug specificity
  2. MIC dosage
  3. Constant replenishment

You can control the first factor by choosing the most appropriate drug, but not the others. Those are up to the patient, and according to a very recent study, nine in 10 patients may take the drug, but only one in 10 will take it at the right intervals to maintain a sufficient MIC to be effective.

The study followed patients who were prescribed antibiotics (either one per day or three per day) for a lower respiratory tract infection. You'd think coughing one's lungs out would be a pretty good incentive to take one's pills. Instead of relying on patient questionnaires, which patients tend to inflate, this study used electronics to monitor patient compliance. The electronics measured whether the patients took the drugs, at what intervals, and at what dosage.

The study's findings:

One per day: 98% took the drug at the right dosage. But only 48% took it at the right intervals (52% noncompliance).

Three per day: 91% took the drug at the right dosage. But only 11% took it at the right intervals (89% noncompliance).

Here's one last bet. You probably hated pharmacology in school. If you read this far, you probably don't hate pharmacology as much as you thought you did.

About the Author

Bill Landers has been president of OraTec Corp. since 1992. He is also a leading expert on chairside and laboratory periodontal risk assessment technologies, and his essays on periodontal disease have been published in several dental hygiene journals. Landers is a popular speaker and has presented hundreds of continuing education seminars on the microbiology of periodontal diseases.

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