Antibiotics: How Long Is Long Enough?
Cross-posted From our Essential Drugs discussion group, E-DRUG
[An important question: when to stop antibiotics? Andy Gray has made a nice
compilation from NY Times and BMJ. Crossposted with thanks from Druginfo. WB
Do you still tell your patients to "complete the course" when prescribing or
dispensing antibiotics? For all infections? This NYT story - here as "fair use"
- contains a controversial statement: "Patients should never assume they can
safely taper treatment on their own when they start to feel better". Some may
disagree, arguing that with most respiratory tract infections, patients or
carers should be told to stop the antibiotics 2 days after the fever subsides,
regardless of how many doses have been taken. The BMJ abstract referred to is
Anyone care to take up the argument?
Antibiotics: How Long Is Long Enough?
By DEBORAH FRANKLIN
Published: June 20, 2006
The arsenal of antibiotics strong enough to squelch nasty bacteria is rapidly
dwindling worldwide, which makes worried infectious-disease doctors more intent
than ever that the drugs be deployed only when strictly needed.
These specialists know that every antibiotic carries its own risks, and that
the more frequently and broadly a drug is used, the more likely it is that
harmful microbes will develop tricks to sidestep it. But a team of researchers
in the Netherlands, where a more selective use of antibiotics has led to much
lower levels of resistant bacteria than are circulating in the United States,
thinks the medical finger-waggers have not gone far enough.
"As doctors, we've paid a lot of attention to questions of which antibiotics we
should use to treat what sorts of infections, but have focused much less on how
long that treatment should last," said Dr. Jan Prins of the Academic Medical
Center in Amsterdam.
In a small but provocative study published in the June 10 issue of the British
medical journal BMJ, Dr. Prins and colleagues from nine hospitals suggested
that even some cases of pneumonia * a potentially life-threatening disease *
could be treated with a three-day course of antibiotics, rather than the
conventional 7- to 10-day treatment.
The Dutch study analyzed the cure rates of 186 adults who had been hospitalized
with mild to moderately severe pneumonia. All received three days of
intravenous amoxicillin to start. After that, the 119 who were showing
substantial improvement were randomly divided into two groups; about half
continued with another five-day course of oral amoxicillin, and the others got
look-alike sugar pills. Neither the patients nor the doctors knew who was
getting which treatment until the end of their participation in the study.
By the end of treatment, roughly 89 percent of the patients in each group were
cured of their lung infections without further intervention. In a commentary
accompanying the study, Dr. John Paul, a microbiologist at Sussex County
Hospital in Brighton, England, writes that, at least for a subset of patients
with uncomplicated, community-acquired pneumonia, the finding "suggests that
current guidelines recommending 7-10 days should be revised."
As lead investigator of the Dutch study, Dr. Prins was not ready to go quite
that far. He cited the study's small size and the seriousness of the illness as
a reason to wait until the finding is independently replicated before advising
a wholesale change in practice.
"This is just the first paper, but I do hope others will have the courage to
test this," Dr. Prins said.
Treatment decisions, he added, should be guided by science, not tradition.
Dr. Michael Fine, a pneumonia expert at the University of Pittsburgh, said he
agreed with Dr. Prins that American doctors should cut back on their use of
antibiotics, particularly against many respiratory infections, which are either
caused by a virus or would get better on their own without treatment. "But I
wouldn't start with pneumonia, where the risk of undertreatment is so great,"
Dr. Fine said. "In terms of drug resistance, we have much bigger fish to fry."
In the United States, amoxicillin is not even the antibiotic of choice in
treating pneumonia, Dr. Fine said, partly because, unlike in the Netherlands,
overuse of penicillins and other broad spectrum antibiotics for acute
bronchitis, earaches, clogged sinuses, sore throats and colds has caused
widespread resistance in the organisms that cause pneumonia.
Doctors in the United States often cite pressure from patients as the reason
for prescribing an antibiotic "just in case" when the source of an upper
respiratory infection cannot be precisely determined. But Dr. Prins said
doctors in the Netherlands rarely treat sore throats or acute bronchitis with
antibiotics, and their patients seem to accept that * maybe because of the
language doctors use to describe the infection. "We're more likely to call it a
bad cold or the flu, and send them home to rest and drink lots of fluid," he
The results of a 2002 study comparing antibiotic use by Dutch and Belgian
doctors in two similar communities bears out the point. Symptoms that Belgian
family practitioners labeled bronchitis, the Dutch doctors called flu or common
colds. The Belgian doctors were also much more likely to prescribe antibiotics.
"My idea in treatment of pneumonia and anything else is that I'd like to use as
much antibiotic as needed, but no more," Dr. Prins said.
For a particular patient, the risks of undertreating should always be taken
into account, he said, "but in the end, consumption of antibiotics determines
resistance rate, and as an individual and as a community, you're going to be
worse off if one day there are no more good antibiotics to treat your
Dr. Ralph Gonzales, an internist at the University of California, San
Francisco, was recently on a panel commissioned by the Centers for Disease
Control and Prevention to develop evidence-based guidelines for the appropriate
use of antibiotics for various illnesses. In their review of the science, Dr.
Gonzales said, the panel found that the evidence for how long a drug needs to
be given varies markedly from illness to illness.
For some ailments * simple urinary tract infections, for example * substantial
research shows that a short course of the right antibiotic works as well as
longer treatments, at least in women under 60. In other ailments, like acute
bronchitis, the best research suggests that antibiotics are almost never
warranted, because the infection is viral, or in other ways self-limiting; the
drugs do not speed recovery. In still other cases, like acute sinusitis and
sore throats, for example, antibiotics will definitely help a small fraction of
patients, Dr. Gonzales said. The trick is to figure out which ones.
"There's good evidence that a 10-day treatment with penicillin will stop strep
throat," Dr. Gonzales said, "whereas if you stop the drug after three days or
five days, the patient will tend to relapse. But strep throat only accounts for
about 10 percent of all the sore throats that walk in the door of the clinic."
The leading indicators that an infection might be strep are a sudden onset of a
sore, red throat dotted with white patches, fever and swollen lymph glands, but
no cough or nasal congestion. It is the doctor's job, Dr. Gonzales said, to be
hard-nosed in evaluating the symptoms and perhaps running a laboratory test to
ensure that only those patients with strep get the drug.
Patients should never assume they can safely taper treatment on their own when
they start to feel better, Dr. Gonzalez said. They not only risk strengthening
the bad bug and suffering a relapse if the incomplete drug dose knocks the
bacteria down but not out, but they also contribute to the problem of
drug-resistant microbes setting up shop in their own families and community.
"It can be confusing for patients, but both undertreatment and overuse of
antibiotics promote drug resistance," Dr. Gonzales said. "Undertreatment is the
match, but overuse is the gasoline poured on the fire."
BMJ 2006;332:1355 (10 June), doi:10.1136/bmj.332.7554.1355
Effectiveness of discontinuing antibiotic treatment after three days versus
eight days in mild to moderate-severe community acquired pneumonia: randomised,
double blind study
Rachida el Moussaoui, clinical research fellow1, Corianne A J M de Borgie,
clinical epidemiologist2, Peterhans van den Broek, professor of infectious
diseases3, Willem N Hustinx, internist in infectious diseases4, Paul Bresser,
pulmonologist5, Guido E L van den Berk, resident6, Jan-Werner Poley, resident7,
Bob van den Berg, pulmonologist8, Frans H Krouwels, pulmonologist9, Marc J M
Bonten, professor of infectious diseases10, Carla Weenink, pulmonologist11,
Patrick M M Bossuyt, professor of clinical epidemiology2, Peter Speelman,
professor of infectious diseases1, Brent C Opmeer, clinical epidemiologist2,
Jan M Prins, internist in infectious diseases1
1 Department of Internal Medicine, Division of Infectious Diseases, Tropical
Medicine and AIDS, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam,
Netherlands, 2 Department of Clinical Epidemiology and Biostatistics, Academic
Medical Center, Amsterdam, 3 Department of Internal Medicine, Leiden University
Medical Center, Leiden, Netherlands, 4 Department of Internal Medicine,
Diaconessenhuis, Utrecht, Netherlands, 5 Department of Pulmonology, Academic
Medical Center, Amsterdam, 6 Department of Internal Medicine, Onze Lieve Vrouwe
Gasthuis, Amsterdam, 7 Department of Internal Medicine, Sint Lucas-Andreas
Hospital, Amsterdam, 8 Department of Pulmonology, Sint Lucas-Andreas Hospital,
9 Department of Pulmonology, Onze Lieve Vrouwe Gasthuis, 10 Department of
Internal Medicine, University Medical Center Utrecht, 11 Department of
Pulmonology, Kennemer Gasthuis, Haarlem, Netherlands
Correspondence to: J M Prins email@example.com
Objective To compare the effectiveness of discontinuing treatment with
amoxicillin after three days or eight days in adults admitted to hospital with
mild to moderate-severe community acquired pneumonia who substantially improved
after an initial three days' treatment.
Design Randomised, double blind, placebo controlled non-inferiority trial.
Setting Nine secondary and tertiary care hospitals in the Netherlands.
Participants Adults with mild to moderate-severe community acquired pneumonia
(pneumonia severity index score 110).
Interventions Patients who had substantially improved after three days'
treatment with intravenous amoxicillin were randomly assigned to oral
amoxicillin (n = 63) or placebo (n = 56) three times daily for five days.
Main outcome measures The primary outcome measure was the clinical success rate
at day 10. Secondary outcome measures were the clinical success rate at day 28,
symptom resolution, radiological success rates at days 10 and 28, and adverse
Results Baseline characteristics were comparable, with the exception of symptom
severity, which was worse in the three day treatment group. In the three day
and eight day treatment groups the clinical success rate at day 10 was 93% for
both (difference 0.1%, 95% confidence interval - 9% to 10%) and at day 28 was
90% compared with 88% (difference 2.0%, - 9% to 15%). Both groups had similar
resolution of symptoms. Radiological success rates were 86% compared with 83%
at day 10 (difference 3%, - 10% to 16%) and 86% compared with 79% at day 28
(difference 6%, - 7% to 20%). Six patients (11%) in the placebo group and 13
patients (21%) in the active treatment group reported adverse events (P = 0.1).
Conclusions Discontinuing amoxicillin treatment after three days is not
inferior to discontinuing it after eight days in adults admitted to hospital
with mild to moderate-severe community acquired pneumonia who substantially
improved after an initial three days' treatment.
Andy Gray MSc(Pharm) FPS
* Senior Lecturer
Dept of Therapeutics and Medicines Management
* Study Pharmacist
Centre for the AIDS Programme of Research
in South Africa (CAPRISA)
Nelson R Mandela School of Medicine
University of KwaZulu-Natal
PBag 7 Congella 4013
Tel: +27-31-2604334/4298 Fax: +27-31-2604338
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