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[afro-nets] Antibiotics: How Long Is Long Enough?

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

Hi all,

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 
also appended.

Anyone care to take up the argument?

Antibiotics: How Long Is Long Enough? 
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 


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
South Africa
Tel: +27-31-2604334/4298 Fax: +27-31-2604338
email: or

Leela McCullough, Ed.D.
Director of Information Services

30 California Street, Watertown, MA 02472, USA
Tel: +617-926-9400    Fax: +617-926-1212

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