Antibiotics abridged - Unnecessarily long prescriptions may fuel drug resistance.

Cutting the length of time that patients take certain antibiotics could help to tackle the rise in drug resistance. So say the authors of a study showing that just three days' worth of drugs can fight pneumonia just as well as a longer treatment.

Many antibiotics are prescribed for a week, ten days, or more, and patients are usually told to finish the course of pills to ensure that all the infection-causing bugs are eradicated. It is widely thought that not finishing the full course of drugs may allow a few of the hardiest bugs to linger, raising the risk that an antibiotic-resistant population of bacteria can then develop.

But there is no particular reason for the length of some antibiotic treatments, says infectious-disease expert Jan Prins of the Academic Medical Center in Amsterdam, the Netherlands. In general, the drugs are given for five, seven or ten days simply because that's what worked in the initial trials.

Three-day cure

Prins and his colleagues decided to test the conventional wisdom. They studied people admitted to Netherlands hospitals with pneumonia, because respiratory tract infections of this type are one of the most common reasons that antibiotics are prescribed. The standard length of antibiotic treatment for pneumonia is 7-10 days.

The researchers treated each patient with a three-day intravenous course of the antibiotic amoxicillin. Of the 119 who improved, half continued to receive antibiotic pills for another five days, and another half were given a placebo pill.

Four weeks after the start of treatment, nearly 90% of patients in both groups were considered cured of the infection. Three days' worth of drugs was enough to kill most of the bacteria; the other five seemed to be superfluous.

At least for pneumonia, the finding counters the idea that a fleeting dose of antibiotics might allow some resilient bugs to survive and develop antibiotic resistance. "There's no reason to assume you leave semi-resistant bacteria behind," Prins says. Their results are published in the British Medical Journal¹.

Testing time

In fact, the reverse could be true: unnecessarily long drug courses could fuel overuse of antibiotics and actually encourage bacteria in our guts to acquire and spread resistance. The recommended time course for some other antibiotics for ear and urinary tract infections has already been shortened because of similar studies; for some types of throat infection, the use of antibiotics is discouraged altogether because most patients get better on their own.

"There is always the possibility that a lower dose or shorter duration might be equally efficacious," says infectious disease specialist Jim Wilde at the Medical College of Georgia, Augusta.

Medical researchers now have to prove that other antibiotic courses can be shortened, by testing each infection and each antibiotic treatment in similar studies. "You have to find out for each infection which is the best course," Prins says.

Until those results are in, the researchers are keen to emphasize that patients should not stop taking their prescribed antibiotics prematurely. For many infections there is strong evidence that the drugs should be taken for a week or longer.

"You want to treat not too little and not too long," says Wilde. "But in many cases you don't have the exact number."

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As I said, I don't see how a continuous LONGER single use term of antibiotics can possibly cause antibiotic resistance compared to a SHORT single use term. I can easily understand how the reverse is possible, though.

"The development of resistance may be reduced by avoiding subtherapeutic antibacterial exposure and prolonged treatment durations."

There was a reason that I used that sentence from that abstract to make the link in comment # 17.

These bugs are acquiring resistance all the time through spontaneous mutations, plasmid acquired genes, etc. especially under prolonged treatment whether it's from monthlong courses for bacterial endocarditis, osteomyelitis, really prolonged acne treatment or controversial Lyme disease recommendations. Thanks for the tip about azithromycin, but I can write my own scripts.

I agree with your assessment, especially because I find the headline misleading. It is one thing to administer IV antibiotics for three days, another entirely if the antibiotics are administered orally.

The general rule of thumb is two to three days after symptoms are gone, so no bacteria remain to cause relapse and become resistant to the antibiotic. Most prescriptions are of sufficient duration to accomplish this.

It has been my understanding that the resistant strains were the product of unfinished treatment i.e., people who quit taking the medication as soon as they felt better, not the product of taking the antibiotics for too long.

"These bugs are acquiring resistance all the time through spontaneous mutations, plasmid acquired genes, etc. especially under prolonged treatment whether it's from monthlong courses for bacterial endocarditis, osteomyelitis, really prolonged acne treatment or controversial Lyme disease recommendations."

Sorry, but I still don't believe that a long SINGLE CONTINUOUS COURSE can cause bacteria to develop antibiotic resistance. ALL bacteria acquire resistance through spontaneous mutations, acquired genes, etc. but please explain how they do so IF YOU'VE KILLED THEM ALL, and then continue the antibiotics in a continuous dose after they're all dead. The problem is FAR more likely from folks who DON'T actually take a single continous course, but "think they're recovered" but actually have NOT killed all the bugs, have symptoms flare up, and then re-start the antibiotics. Or doing stupid things like adding antibiotics to animal feed as a "preventative".

ALL bacteria acquire resistance through spontaneous mutations, acquired genes, etc. but please explain how they do so IF YOU'VE KILLED THEM ALL, and then continue the antibiotics in a continuous dose after they're all dead.

That's just it. Antibacterial antibiotics don't kill them all. They interfere with basic cellular processes. They have been divided into two main classes, bactericidal and bactertiostatic. Don't ask me who made or why this classification was made. I'm not a microbiologist.

Those that are in the beta lactam class, i.e. the penicillins and cephalosporins, inhibit bacterial cell wall synthesis, and they are usually called bactericidal, even though they are not killing the organism, just inhibiting the growth of cell walls of new bugs.

Most of the drugs mentioned on the previous acne link are bactertiostatic which inhibit protein synthesis at various ribosomes. Drugs like Cipro, in the class called flouroquinolones, inhibit DNA gyrase, the enzyme that bacteria need to uncoil its DNA prior to replication.

These drugs are not killing. They just inhibit basic functions needed to replicate. Literal killing is only done by a reasonably intact immune system.

"These drugs are not killing. They just inhibit basic functions needed to replicate. Literal killing is only done by a reasonably intact immune system."

Sorry, but this is a distinction without a difference. Since they can't replicate, they can't pass on any "acquired antibiotic resistance". Then they die. And yes, I know that antibiotics don't kill 100.000%, just knock the numbers down to a level where the immune system can handle the rest.

This STILL doesn't address the point that an UNINTERRUPTED DOSAGE SCHEDULE "longer than standard" should not increase the acquistion of antibiotic resistance.

From the article:

"...this can be of major importance in decreasing antibiotic consumption. On a population level there is a clear relation between total antibiotic consumption and resistance rates of the pathogens.6-8 Prolonged or repeated courses of antibiotics provide the selective pressure that favours the emergence of resistant isolates. Resistance rates among common respiratory pathogens for several antimicrobial agents are increasing.9 Decreasing the duration of antibiotic treatment in respiratory tract infection might therefore decrease resistance rates.

The article in no way addresses AT ALL the acquisition of antibiotic resistance on a "single patient" level.

And from your "follow-up" link:

"Notably, therapeutic exposure of bacteria to antibacterials exerts a continuous selection pressure on pathogens as well as on normal flora. This selection pressure may favor and/or enable resistance development through various mechanisms. The development of resistance may be reduced by avoiding subtherapeutic antibacterial exposure and prolonged treatment durations."

Likewise this statement doesn't define by what mechanism a "prolonged treatment duration" results in the acquisition of antibiotic resistance.

My contention is that a CONTINUOUS course of treatment is unlikely to so result, but that "prolonged treatment durations" allow an increased liklihood of DISCONTINUOUS treatment, which, I can easily see explaining any such population effects.

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Story from news@nature.com: http://news.nature.com//news/2006/060605/060605-14.html