17-12 Antibiotics


Since the introduction of antibiotics in World War II, doctors have prescribed courses of treatment that typically ran longer than necessary. Bacterial resistance is forcing a reevaluation, shortening courses sometimes to just a few days and even prompting doctors to advise not using all pills if patients feel better.

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  • Dr. Brad Spellberg, Chief Medical Officer, Los Angeles County-University of Southern California Medical Center
  • Dr. William Schaffner, infectious disease specialist, Vanderbilt University Medical Center
  • Dr. Louis Rice, Chairman, Department of Medicine, Warren Alpert Medical School, Brown University

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Shortening the Course of Antibiotics

Reed Pence: Perhaps nothing has changed medicine more over the last century than the advent of antibiotics. Given the toll exacted by infectious diseases before the drugs availability, antibiotics may have seemed almost too good to be true.

Dr. Brad Spellberg: Antibiotics have been around now for about 80 years and when they first came along there were enormous, enormous declines in death from infections. In fact, frankly antibiotics were the first effective therapy that modern physicians had.

Pence: That’s Dr. Brad Spellberg, Chief Medical Officer at the Los Angeles County University of Southern California Medical Center.

Spellberg: The problem with them is, that because of transmission of resistance – the more we use them, the faster we lose them. For many years, resistance would catch up with our current antibiotics and the pharmaceutical industry would go back to the drawing board and bring out the next generation of [unintelligible]. But that equation is beginning to change, that’s not financially attractive to invest in new development of antibiotics. The science has become hard, the stuff that’s easy to discover – we discovered, so it’s getting increasingly difficult to find the next generation of antibiotic. And what that means, we’re not getting bailed out anymore. And because of that, resistance rates are rising through the roof and death rates from the resistant infections are going up. And we’re seeing patients that we simply can’t treat.

Pence: Overuse of antibiotics is driven by how doctors have prescribed them. Remember getting prescriptions for 2 weeks worth of antibiotics and then being told to take all of them, even if you felt better before then? It’s what every patient was told – for decades.

Dr. William Schaffner: When antibiotics first came on the scene the general notion of all those doctors, 60 and 70 years ago, was “ we better be sure the infection is treated.”

Pence: Dr. William Schaffner is an infectious disease specialist at the Vanderbilt Medical Center in Natshiville.

Dr. William Schaffner: And so, the duration of therapy tended to be rather ‘long-ish’ and for the average infection – urinary tract infection, bladder infection, and you know simple pneumonia – 10 days to 2 weeks was thought to be appropriate and perhaps we are going to give antibiotics a little longer just to be sure we cured the infection. Because back then, people weren’t sure how quickly antibiotics could cure infections.

Spellberg: Experts at the time were writing things like, “we treat until the patient feels better and another couple of days to prevent relapses.” Turns out that they weren’t actually preventing relapses, they were preventing infections by a new strain of bacteria’s. So the root of the urban legend itself seems to reflect the misunderstanding of what was happening at the time. So we have this sort of duration creep that happened and because of this sort of urban legend people said, “Well just keep going until you’re done even if it’s two weeks, even if you felt better at day 5,” which is complete nonsense.

Pence: In fact, Spellberg says medicine sort of fell into its prescribing courses.

Spellberg: The standard duration of treatment for most infection is really based on a 1696-year-old creed from Constantine the Great. He decide there would be 7 days in a week, so when we pick durations of therapy, we go “oh, just gonna give 14 days!” Why 14? Well that’s two Constantine units. If Constantine had picked 4 days in a week – we’d be treating for 8 days. It’s extremely arbitrary how we decide how long to treat.

Pence: Heeding an urban legend based on an arbitrary calendar is no way to practice medicine. But doctors in the 40’s and 50’s just wanted to kill the infection, they didn’t think much about bacterial resistance. In fact, Schaffner says the original belief was resistance was rare. But in reality bacteria are built for it. They’ve been using their own antibiotics on each other in a big way for millennia.

Spellberg: Antibiotics were invented by bacteria, probably on the order of 2 billion years ago with at B, and they’ve been killing each other with these weapons for 20 million times longer than we’ve even known they exist. So what that tells us is, that already wide spread in nature are resistance mechanism that will create resistance to drugs that we haven’t yet even invented. When we use an antibiotic, what we do is kill off the susceptible bacteria and leave behind the very tiny amounts of bacteria that were already resistant so that they can replicate and spread their resistance mechanisms. So, it’s not that resistance emerges anew when you use an antibiotics, it’s that you select out for pre existing resistance. And that means, the more you use, the more resistance you will select for.

Schaffner: The antibiotics rather quickly kill the bacteria that are susceptible and the very few that are there genetically disposed to be resistance, they then have an opportunity to grow up and become more prominent. And certainly what we’ve learned is, the more antibiotic you use, the longer you use antibiotics, the more likely it is that these resistant bacteria will flourish and become dominant.

Pence: That’s why Schaffner and Spellberg say the next time you go to the doctor with an upper respiratory infection or some other bacterial malady, you may get different instructions than what we’ve been getting for decades. Doctors are now likely to prescribe a shorter course of antibiotics than they used to.

Schaffner:  The trick would be to treat just as long as is necessary in order to treat the infection, but not a day longer. Because, then it’s useful and the additional antibiotic that extra day or two, would only be serve then to create more resistance.

Spellberg: In the last 10 years or so we have begun to conduct clinical trials that compare different durations of therapy and in virtually, not quite all, but in virtually all of those trials – the shorter course regimens have worked just as well as longer courses – so we know we can begin to shorten. Now, I know that if I have a patient with a kidney infection, 5-7 days of antibiotics is gonna work just as well as 14. What about 3 days? We don’t know, we haven’t done that trial yet. So the mantra really has become, “shorter is better.” Now if I give you a 5-day course of antibiotics for your skin infection, it’s pretty unlikely you’re gonna be feeling enormously better much before day 5. If I gave you a 14 –day course, you would feel better by day 5 or 6 and have a whole week of therapy left that was a complete waste.

Pence: Some of the differences in the length of treatment that works vs. what’s been traditionally prescribed are truly striking.

Schaffner: Urinary tract infections, bladder infections – these are very very common – and we used to give treatments for a week/a week and a half. But what’s remarkable for uncomplicated infections, where nothing anatomic is also a problem, we can now know we can treat those infections for only two days and not only does the patient feel better but then infection is completely treated.

Dr. Louis Rice: In most cases, when we’ve looked at it, we’ve been able to show that shorter courses are equally effective.

Pence: Dr. Louis Rice is Chairman of the Department of Medicine at the Warren Alpert Medical School of Brown University. He is often credited with being the first to call long prescribing regimens into question.

Rice: In the hospital there have been a couple of different important pneumonia studies, one showing that 3 days of therapy is equivalent to, on average, was 9 days and had less resistance and other shortened therapy from 15 days down to 8 days for people on ventilators. There was a recent study about a year ago that looked at intra abdominal infections that showed that a shorter course was as effective, back in 2006 there was a study published from Europe it showed that community pneumonia and a course of 3 days was equivalent to a 7 or 8 day course.

Pence: But it’s even more than that, some doctors may tell you to quit taking your medication when you feel better even if you have pills left over.

Spellberg: Then I can have the discussion with you, “look, I’m gonna give you 5 days of antibiotics for a skin infection. If day 3 or 4 comes along and it’s gone – give me a call, we can talk about stopping early.”

Rice: If it’s not that serious an infection it’s probably not a terrible idea to tell a patient, “when you’re feeling better it’s probably ok to stop the antibiotic.” Most mild infections are like that, you can just give a couple of days of antibiotics, many of the antibiotics we have that see very good levels in the body, relative quickly, they kill bacteria fairly quick and most people have an immune system. Many of the antibiotics we give don’t actually kill bacteria, they just keep them from multiplying and it’s the immune system that actually takes care of it.

Pence: But one person’s robust immune system may be another’s weak immunity. So doctors can never be sure how many days are enough for any given person and rice says some physicians are hesitant to shorten courses very much. More studies into how many days are required for different kinds of infections will continue to be important.

Rice: The National Institute of Health in this country are now sponsoring a number of studies, very grateful to them for it that they’re looking at durations and other things as well and what would really be nice is if we could identify some other test, some blood test that could tell us, “Ok you don’t need antibiotics anymore.” Because for the same infection, I may need three days, you may need four. Somebody else may need 7, somebody else may be cured after one. There’s such a different interplay, the nature of the infection, the nature of the bacteria, the strength of somebody’s immune system, that all comes in to it. So it’s really naïve to think that, with as varied a population as we have, we’re gonna have everybody needing only this number of doses.

Pence: And not only is the issue of bacterial resistance important, but the longer the course of antibiotics, the more likely there is side effects. Rice says that it’s a worthwhile discussion to have with your doctor to ask, “how much do I really need to cure this?” If enough of us do that, Schaffneer says it could be a sizeable dent into resistance.

Schaffner:  There’ve been a number of studies that would encourage us if we are more prudent about the use of antibiotics; using them for shorter periods of time and not using them in certain stances where the infection is not going to respond – a viral infection for example – viruses don’t respond to antibiotics. If we study populations over time we can see that the bugs are restored to their susceptibility, so resistance in that population of bacteria is reduced. So it’s as though we’re turning back the clock.

Pence:But if we don’t protect the antibiotics we have, Spellberg says the stakes are extremely high.

Spellberg: We risk losing the gains made from effective antibiotics. Those gains would include probably about a 20 year average increase in lifespan, the availability of intensive surgeries which you could not do because of lethal infections before antibiotics, cancer chemo-therapy would kill people from the infections without antibiotics, organ transplantation, care for premature babies, there’s a whole variety of medical interventions, the availability of which depends on having antibiotics to combat the infections that result.

Pence: You can find out more about all of our guests on our website, RadioHealthJournal.net. You can also find archives of our programs there as well as on iTunes and Stitcher. I’m Reed Pence.

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