Jul 28 2017

Should You Complete That Course of Antibiotics?

antibiotic-resistanceAs with most things, the answer is more complicated than it may at first seem.

Up to now the official answer was simple – always finish prescribed courses of antibiotics. Stopping early, it was argued, could increase the risk of antibiotic resistance. The idea is that bacteria which are a little resistant to the antibiotic will survive longer, and if they are not wiped out by completing the course, the partially resistant bugs will then reproduce, with random mutations leading to greater resistance. The antibiotics are essentially a selective pressure leading to resistance.

This makes sense, and is almost certainly true with certain chronic infections, such as tuberculosis.

A new review, however, suggests that we cannot apply this rule simplistically to all infections. It depends on the type of bacteria involved.

Some bacteria exist in the body as part of our normal flora. Mucous membranes are colonized with bacteria, for example. If, however, those same friendly bacteria get into the wrong place, like the lungs or the blood, they can cause an infection. In such cases, the longer the course of antibiotics, the more likely bacteria living in the body will develop resistance. If they ever cause an infection, that infection is therefore more likely to be resistant to the antibiotics previously used.

So in essence there are two factors at cross purposes – completing a course of antibiotics to prevent partially resistant bacteria from surviving, and minimizing the course of antibiotics in order to minimize overall selective pressures on evolving resistance (for the target bacteria and other bacteria in the body).

We therefore need to balance these two concerns.

What the authors of the review argue is that the evidence for completing a course of antibiotics in order to reduce the risk of resistance is lacking. Since, they argue, that we do not know that completing a course is a risk, but we do know that longer antibiotic use is a risk for resistance, the recommendation to complete antibiotic courses in all cases is not optimal.

In fact, they argue that the concept of an “antibiotic course” is outdated and not evidence-based. An “antibiotic course” is essentially a predetermined length of time for which specific antibiotics should be taken to treat a specific infection. For many infections there is evidence that certain durations are important for effectiveness, but not necessarily to minimize resistance.

The alternative approach is to individualize antibiotic treatment duration. This could mean substituting another factor for duration, such as resolution of symptoms. In some situations it could also mean resolution of abnormal findings on laboratory tests or imaging studies. These other factors are already incorporated into evaluating patients with infections and monitoring their response to treatment. The question is – do we rely more on these symptoms and laboratory test factors, or adhere to predetermined lengths of treatment?

Where does this leave us?

What is the bottom line take-home message from this review? Well, the CDC has  already changed the wording of its recommendations to the public from “complete the course” to “take exactly as prescribed.” That is a more general recommendation that essentially means, just do what your doctor tells you to do.

That is good advice. Essentially what this review is telling us is that antibiotic treatment duration is complicated, and determining the optimal duration needs to be more individualized and account for more information. Every type of infection might have its own parameters – some may require a specific course duration, others may rely on specific symptoms or tests. The number of variables is huge.

What this review does not mean is that patients should stop all antibiotic courses when they feel better. That is also an overly simplistic algorithm that is likely to be suboptimal, and may result in a partially treated infection (a potentially serious outcome).

Instead, doctor’s recommendations will have to become more nuanced. We also need more research to better inform these decisions. This is also another area where expert systems could be highly useful – crunching all the variables to make optimal prescribing recommendations.

13 responses so far

13 thoughts on “Should You Complete That Course of Antibiotics?”

  1. BenE says:

    Interesting.

    Although there’s always risk that when you add complexity to a system (or a treatment), user acceptance goes down.

    In cases of ambiguity, people don’t do the rational thing and dedicate more brainpower to researching expert advice and best practices to make a better informed decision. Instead, they feel like “well, anything could be fine”, so they do something far more dangerous – whatever they feel like. And whatever they feel like is not typically the optimal treatment. Worse, they start discounting expert advice because they perceive contradictions in expert advice.

    I fear people will go through a thought process like “Well, I’ve always heard that you should take all your antibiotics regardless, but now my doctor says it’s fine to stop taking if I’ve been symptom-free for four days. I don’t think they really know what they’re talking about. They can’t even agree. I’ll just take it until I feel better. And then discount expert advice going forward.”

  2. BillyJoe7 says:

    I don’t understand the conclusion of this post:

    “What is the bottom line take-home message from this review?
    Well, the CDC has already changed the wording of its recommendations to the public from “complete the course” to “take exactly as prescribed.” That is a more general recommendation that essentially means, just do what your doctor tells you to do.
    That is good advice”

    What is the difference between “complete the course” and “take exactly as prescribed”?

    The whole point of the post seems to be that doctors don’t know what what to tell you; or that what doctors tell you is not based on scientific evidence.
    So, how can the conclusion be to do as your doctor tells you?

  3. BillyJoe7 says:

    And what does this sentence mean:

    “Since, they argue, that we do not know that completing a course is a risk, but we do know that longer antibiotic use is a risk for resistance, the recommendation to complete antibiotic courses in all cases is not optimal”

    Shouldn’t that be…

    Since, they argue, that we do not know that not completing a course is a risk, but we do know that longer antibiotic use is a risk for resistance, the recommendation to complete antibiotic courses in all cases is not optimal.

  4. tb29607 says:

    BJ,

    After reading the referenced review my interpretation is that the point when antibiotics should be stopped may change from a specific number of days to other end points points such as symptom resolution. So in the future you may be given 14 days worth of an antibiotic with instructions to take it until you have been without fever for 24 hours and then stop. So you would not be completing the 14 day course and instead “taking as prescribed”.
    And yes, I believe your revised sentence is more consistent with the review article.

    I support the basic message of the review, that shorter courses are often equally effective for the acute infection being treated and reduce resistance in opportunistic pathogens. However I think the review is misleading in regards to resistance in recurrent infections due to treatment failure. There is ample evidence of this in the pediatric literature, such as studies showing recurrent infections from treatment failures of acute otitis media (ear infections) are from newly resistant organisms.
    Also, azithromycin treatment failures of Strep pharyngitis results in resistant Strep bacteria. The authors dismiss this as “clinically insignificant” and they may be proven correct. However, consider the well documented phenomenon of “gateway resistance”, whereby bacteria which develop any initial resistance are subsequently much more likely to develop high level resistances, often to unrelated antibiotics which there had previously never been resistance to. Azithromycin resistant Strep throat bacteria may not be clinically problematic currently, but should not be dismissed in order to preserve the (highly questionable) narrative that there is “no evidence of resistance in recurrent infections from treatment failures”.

  5. zorrobandito says:

    “I fear people will go through a thought process like ‘Well, I’ve always heard that you should take all your antibiotics regardless, but now my doctor says it’s fine to stop taking if I’ve been symptom-free for four days. I don’t think they really know what they’re talking about. They can’t even agree. I’ll just take it until I feel better. And then discount expert advice going forward.'”

    Well that’s certainly what I am thinking. My physician, a super-busy GP, doesn’t have a clue about how or why to “individualize” her instructions in this area. Now that I’ve read this summary I’m willing to bet that I know more about it than she does, which, to be fair to both of us, is almost nothing in either case.

    What I have learned, though, is that there isn’t much scientific basis for “finish the course of antibiotics” but the CDC doesn’t really have anything better to substitute for it, so they’re tossing this decision out to overworked GP’s to “nuance.” Great.

    What I will do if confronted with this poorly-defined mess is to take the entire course of antibiotics. There isn’t much (or sometimes any) evidence either way, but it’s hard to see the downside.

  6. tb29607 says:

    zorrobandito,

    You are absolutely correct that the best current action is to complete the course of antibiotics. The review advocates treatment end points based on symptoms and/or laboratory markers of inflammation instead of a specified number of days. This seems reasonable and makes intuitive sense but as the authors state, studies are needed to determine the best indication to stop and to determine if this strategy is better. The potential “real world” difficulties of implementing such a strategy are a big concern. I have many families who struggle to remember when and how often to give medication their child has been on for years. I doubt less concrete instructions would improve adherence.

    The best supporting study was for treating outpatient pneumonia. Outpatient treatment indicates these are in mild category of these infections, and patients were directed to take antibiotics for 5 days after their last fever. There are excellent studies showing that no antibiotic regimen alters the disease course of pneumonia until after 3 days of effective treatment. The average length of treatment in their model study was, predictably, just over 8 days on average. Current recommendations are for 10-14 days based on severity, so their symptom based strategy reduced length of treatment by 2 days.

    The review states, but does not stress, that studies for the vast majority of other infections have not been done. The study cited on ear infections showed more treatment failures with shorter courses. They also did not address prior studies which obtained cultures of middle ear infections at presentation and again for treatment failures which showed development of resistance in the recurrent infection.

    I am in the process of obtaining the cited studies on Group A Strep pharyngitis. Previous studies showed increased incidence of Rheumatic Fever (RF) with less than 10 days of antibiotics. RF can cause many debilitating problems, one of the worst being life threatening damage to heart valves.

    One type of infection not included is urinary tract infections (UTI). The length of treatment for UTI has been greatly reduced recently and I have not found any evidence of increased complications.

    I am not done looking at the other studies cited in the review but my opinion so far is that the authors (including a retired building surveyor) are advocating a reasonable overall strategy. Disease and age specific studies are needed and I think they want to encourage research in this direction. As with any large, heterogeneous entity, significant change will take time, and involve large scale discussions. This is an interesting topic but new treatment recommendations are probably a few years away.

  7. BillyJoe7 says:

    tb,

    “So in the future you may be given 14 days worth of an antibiotic with instructions to take it until you have been without fever for 24 hours and then stop”

    That would make the post read more sensibly, but “in the future” is not mentioned anywhere.
    On the contrary, there’s this:

    SN; “Up to now the official answer was simple – always finish prescribed courses of antibiotics”

    Does your GP know how long you should take penicillin for a strep throat?
    And, if they do, why have they not stating that on the prescription?
    (ie Penicillin 500mg X 20 tabs: take 1 tablet four times a day for 5 days)

    And what’s the actual meaning of “a course of antibiotics”?
    Is it whatever the pharmaceutical company decides to put in the box of antibiotics?

  8. BillyJoe7 says:

    …oops, I just read your last post.
    Make that…Penicillin 500mg X 40 tabs: take 1 tablet four times a day for 10 days

  9. GrahamH says:

    ‘Nuanced recoomendations’
    As the effects of treatments are better understood they CAN become more finely tuned wrt the individual patient.
    As the saying goes ‘that sounds fine in theory, but how does it work in practice?’

    I would love to know more about the doctor/patient interactions. The move away from paternalism is great for those of us who read the monograph etc., ask those questions when we don’t understand. However, snd unfortunately, there is a large segment (perhaps a majority even?) who would respond better to an authority figure.
    I’m all for the patient being educated, but many don’t want to be. An interesting dilemma.

  10. tb29607 says:

    BJ,

    I suspect most GP’s know the length of treatment for Strep pharyngitis. The dose, timing, and duration should be stated clearly on every prescription. If these are not clearly stated on the prescription I would ask the pharmacist why not because that information is required for the prescription to be filled.

    Course of antibiotics is the dose, timing, and length of treatment. Many were determined in the 60’s and 70’s (frequently by the military) with some studies being better than others. The Strep pharyngitis studies were some of the better ones. The Kawasaki’s disease study from the 70’s is a notably bad one and yet still guides treatment today.

    GrahamH,

    May anecdotal observations have been that patients/families who prefer the paternalistic approach gravitate to doctors who tend toward paternalism. Patients/families who want to understand, read, and be educated usually do not tolerate paternalistic doctors and find one more agreeable to the desire for understanding.

  11. BillyJoe7 says:

    tb,

    “The dose, timing, and duration should be stated clearly on every prescription…Course of antibiotics is the dose, timing, and length of treatment”

    Then I’m back to my original question:

    “What is the difference between “complete the course” and “take exactly as prescribed”?”

    I’m still totally confused by this post and the article on which it is based.

  12. tb29607 says:

    BJ,

    My interpretation is that “take exactly as prescribed” is to allow for a treatment plan where, as a generic example, a person is given 14 days worth of antibiotics, directed to take them until their fever is gone (or some other symptom) and may result in some doses not being taken. I agree it is a bit ambiguous and seems to assume that a course of antibiotics is defined by the number of doses in the prescription.

  13. Bill Openthalt says:

    What to do with people like my mother-in-law, who takes her medications exactly as she sees fit. She’s in her 80ies, and has a cupboard full of every medication she’s ever been prescribed in her life. It goes as follows: when prescribed one tablet twice a day, she’ll take half (or even a quarter) in the morning, and save the rest “for a rainy day”, when she’ll auto-medicate as the fancy takes her (including savant mix-and-matches based on her perceived symptoms). She’s recently lost her doctor, whom she had been consulting since yonks, and who would (even though being in his 90ies) send her prescriptions by snail-mail after a telephonic consultation. His successor is half her age, and not trusted at all (mainly because he’s not prescribing what she thinks she needs). Her sister is 10 years older, of similar disposition, and both regularly swap medications (“you should try this one, dear, it does wonders for my swollen ankles/digestion/libido”).

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