5 ms·

This bit of folk/medical wisdom has been around for a few decades, but for the life of me I can't understand the logic - beyond the notion that merely being asy

This bit of folk/medical wisdom has been around for a few decades, but for the life of me I can't understand the logic - beyond the notion that merely being asymptomatic doesn't mean you've killed all the bugs. How this can possibly contribute to the spread of antibiotic resistance is mystifying to me, as is the basis of this advice - is there ANY evidence that patients not completing their drug courses causes resistance?

hga 10y ago
Absolutely! As I learned as a rule of thumb while doing microbiological research in a NSSF Summer Science Training Program in 1977, most random antibiotics would fail to kill E. Coli at a rate of 1 in a million, and it went up to 1 in a billion with streptomycin (this is with random mutations, no plasmid acquisition involved, which is another story). However, these surviving bugs are generally not as fit as wild type, they've probably survived by sacrificing something, or doing something that consumes more energy. This helps your immune system mop them up, and note if antibodies are involved (don't know about that) it takes a while to come up with new ones, plus if there's any sort of bacteria ecology in the target area that survives the antibiotic they'll out-compete them. It shouldn't take much research on your part to confirm the basics of what I've related above, it's a tremendous problem, especially with TB, who's defenses require long and obnoxious drug schedules, resulting in more and more MDR and XDR (multi- and extensively-drug resistant) strains. If you get XDR, you're probably going to die, in a era where that's squalid instead of romantic. And I just came across "Totally drug-resistant tuberculosis" https://en.wikipedia.org/wiki/Totally_drug-resistant_tuberculosis https://en.wikipedia.org/wiki/Totally_drug-resistant_tubercu... Not official yet, but....
- astazangasta 10y ago
  As I said, completing your course is useful in eliminating residual disease. How does it help in preventing drug resistance? If anything it seems by increasing exposure to the drug it encourages the development of resistance, since it gives the (otherwise less-fit) resistant bacteria a fitness advantage. Completing a course of a drug that the bacteria is already-resistant to will accomplish nothing other than eliminating its non-resistant competitors, so what's the logic?
  - photoJ 10y ago
    What's curious about this view, is that it ignores how researchers create AMR bugs in the lab. Namely low doses of Antibiotics to allow time for the bacteria to mutate and develop resistance. If you're interested you can look up MIC Minimal Inhibitory Concentration, I think you would find it illuminating. Also the assertion that the resistant phenotype is "otherwise less-fit" is not accurate.
    - astazangasta 10y ago
      The resistant phenotypes often ARE less fit, as the guy above me said - if you have to run a solute pump in order to remove drug from your cytoplasm, that has a cost in energy and protein. EVERY phenotype has a cost that must be paid. You don't get to hang onto a useless genotype in the absence of a selective pressure that maintains it. Low doses allow you to provide a continuous challenge that doesn't kill the entire population. That's not what's happening when you stop your drug course early.
      - photoJ 10y ago
        DNA absolutely hangs on to useless genotypes for some period of time. Horizontal gene transfer allows for redundant genes to exist. They have increased mutation which MIGHT lead to some productive change, but for an extended period of time they don't. Not to mention biological mechanism which exist for many many generations even though they aren't used in some grow medium. The disagreement here is about time scale. If it were true that resistant phenotypes often ARE dramatically less fit to the degree you imply we could simply stop taking Antibiotics and everything would revert back to it Susceptible state. When you stop a dosage early you've very likely applying a low dosage to some subpopluation. Dosages are not linear, nor evenly applied throughout the entire population of bacteria in a human body.
  - hga 10y ago
    Errr, the theory I'm relating is that continuing the pressure of the antibiotic will make it easier for the body, and perhaps non-susceptible benign bacteria, to finish them off (perhaps not all, but to a de minimus number where they won't pose a problem). Remove that pressure, and the resistant population has a chance to rebound. More likely than having an ecology of other bacteria to fight with is that the field is somewhat or all but completely cleared. The body may not also have had a chance to clear up whatever condition allowed it to get a grip in the first place. Etc. Again, as I understand it TB is a great example to look at, and depending on where you live it might even be a real danger to your and yours, so maybe read up on it?

hga 10y ago

Absolutely! As I learned as a rule of thumb while doing microbiological research in a NSSF Summer Science Training Program in 1977, most random antibiotics would fail to kill E. Coli at a rate of 1 in a million, and it went up to 1 in a billion with streptomycin (this is with random mutations, no plasmid acquisition involved, which is another story). However, these surviving bugs are generally not as fit as wild type, they've probably survived by sacrificing something, or doing something that consumes more energy. This helps your immune system mop them up, and note if antibodies are involved (don't know about that) it takes a while to come up with new ones, plus if there's any sort of bacteria ecology in the target area that survives the antibiotic they'll out-compete them. It shouldn't take much research on your part to confirm the basics of what I've related above, it's a tremendous problem, especially with TB, who's defenses require long and obnoxious drug schedules, resulting in more and more MDR and XDR (multi- and extensively-drug resistant) strains. If you get XDR, you're probably going to die, in a era where that's squalid instead of romantic. And I just came across "Totally drug-resistant tuberculosis" https://en.wikipedia.org/wiki/Totally_drug-resistant_tuberculosis https://en.wikipedia.org/wiki/Totally_drug-resistant_tubercu... Not official yet, but....

astazangasta 10y ago
As I said, completing your course is useful in eliminating residual disease. How does it help in preventing drug resistance? If anything it seems by increasing exposure to the drug it encourages the development of resistance, since it gives the (otherwise less-fit) resistant bacteria a fitness advantage. Completing a course of a drug that the bacteria is already-resistant to will accomplish nothing other than eliminating its non-resistant competitors, so what's the logic?
- photoJ 10y ago
  What's curious about this view, is that it ignores how researchers create AMR bugs in the lab. Namely low doses of Antibiotics to allow time for the bacteria to mutate and develop resistance. If you're interested you can look up MIC Minimal Inhibitory Concentration, I think you would find it illuminating. Also the assertion that the resistant phenotype is "otherwise less-fit" is not accurate.
  - astazangasta 10y ago
    The resistant phenotypes often ARE less fit, as the guy above me said - if you have to run a solute pump in order to remove drug from your cytoplasm, that has a cost in energy and protein. EVERY phenotype has a cost that must be paid. You don't get to hang onto a useless genotype in the absence of a selective pressure that maintains it. Low doses allow you to provide a continuous challenge that doesn't kill the entire population. That's not what's happening when you stop your drug course early.
    - photoJ 10y ago
      DNA absolutely hangs on to useless genotypes for some period of time. Horizontal gene transfer allows for redundant genes to exist. They have increased mutation which MIGHT lead to some productive change, but for an extended period of time they don't. Not to mention biological mechanism which exist for many many generations even though they aren't used in some grow medium. The disagreement here is about time scale. If it were true that resistant phenotypes often ARE dramatically less fit to the degree you imply we could simply stop taking Antibiotics and everything would revert back to it Susceptible state. When you stop a dosage early you've very likely applying a low dosage to some subpopluation. Dosages are not linear, nor evenly applied throughout the entire population of bacteria in a human body.
- hga 10y ago
  Errr, the theory I'm relating is that continuing the pressure of the antibiotic will make it easier for the body, and perhaps non-susceptible benign bacteria, to finish them off (perhaps not all, but to a de minimus number where they won't pose a problem). Remove that pressure, and the resistant population has a chance to rebound. More likely than having an ecology of other bacteria to fight with is that the field is somewhat or all but completely cleared. The body may not also have had a chance to clear up whatever condition allowed it to get a grip in the first place. Etc. Again, as I understand it TB is a great example to look at, and depending on where you live it might even be a real danger to your and yours, so maybe read up on it?