Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.38049.490255.DE (Published 01 April 2004) Cite this as: BMJ 2004;328:791
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The inclusion citeria did not included fever and persistent of fever
was not included as treatment failure. Wheeze was assessed but
crepitation was not mentioned in the study. Viral bronchiolitis and croup
are common diagnosis of respiratory distress in the study age group. So,
antibiotics are not useful. In the study, nasopharyngeal swab was used for
bacterial culture, positive culture may be due to local colonisation.
Competing interests:
None declared
Competing interests: No competing interests
The Editor British Medical journal
Dear Sir,
I have read the article titled “Three day versus five day treatment
with amoxicillin for non severe pneumonia in young children: a multi
centre randomized controlled trial” published in BMJ,
doi:10.1136/bmj.38049 490255. DE (Published 30 March 2004) with a lot
interest. The study group has done a lot effort to produce a very good
work for the benefit of practicing doctors. we have a few observations to
make in the study.
1. Out of the total 2188 patients included in the study, 513 (23.4%)
tested positive for respiratory syncitial virus (RSV) at enrolment. As
these cases did not have a bacterial agent in the aetiology and treatment
with amoxicillin for 3 days or 5 days would not have any effect on them,
these cases should have been excluded from the study.
2. Overall 15% of the Streptococcus pneumoniae (16.4% in three day and
15.5% in 5 day treatment groups) and 18% of the Haemophilus influenzae
(19.6% in 3 day and 16.9% in five day treatment groups) were found
resistant to amoxicillin on enrolment. If we calculate overall resistance
of the isolates to amoxicillin it comes to about 16% (217 resistant out of
1293 both Streptococcus pneumoniae and Haemophilus influenzae). In the
presence of such a high percentage of resistance how come the outcome was
89.5% in the three day and 89.9% in the five day treatment groups
respectively.
3. The cases from which the above isolates were found to be resistant to
amoxicillin at the enrolment were still given/continued amoxicillin or
some other alternate antibiotic was administered to these cases. It
usually becomes difficult for the treating physician to continue an
antibiotic in a case in which lab report of resistance to the causative
bacterial agent becomes available.
4. How come the resistance of Streptococcus pnueominiae to co-trimoxazole
rose from 66.1% to 78.2% over a 15 day period in 5 day amoxicillin group
only while there was no rise of resistance in the 3 day treatment group.
The rapid emergence of resistance only occurs under the selective pressure
of an antibiotic most of the times. So were these cases administered co-
trimoxazole in addition to amoxicillin ?
Dr Abid Mahmood
Consultant Microbiologist
United Nations Level II Hospital
Liberia
Dr Muhammad Yasir
Consultant in Internal Medicine
United Nations Level II Hospital
Liberia
Competing interests:
None declared
Competing interests: No competing interests
Sirs,
I find it most intriguing that you have found both that treatment non
-compliance at 5 days is a factor for treatment failure, and that 3 days
treatment is as efficacious as 5 days. The two findings would appear to
be contradictory, particularly as you have published evidence that
compliance with treatment at day 3 is comparable within the 2 groups. Do
you think that the groups failing to comply with the longer treatment
course were more likely to have presented late, or to come from a more
disadvantaged socio-economic group, or had you an alternative explanation
for this apparent discrepancy?
Competing interests:
None declared
Competing interests: No competing interests
EDITOR- We would like to comment some aspects of the clinical trial
of the ISCAP Study Group in non-severe pneumonia in young children (1) .
Evidence of pneumonia in chest radiograph was not an inclusion criteria.
Due to that, in general practice, chest radiograph can be considered a
pragmatic reference standard for pneumonia (2) , in fact the study was
performed in patients with clinical suspicion of pneumonia but not in
patients with pneumonia. Refering to the criteria of response, they were
not criteria of clinical cure but were criteria of impairement. It can not
be assumed that patients not impaired at 3 or 5 days were cured. Moreover,
standard duration of treatment with amoxicillin in children with pneumonia
is not five days but is 7-10 days (3) . Thus, we consider that three days
treatment arm was not compared to the standard therapy.
Lastly, in the
section corresponding to adverse reactions authors mention that there were
no serious adverse effects of amoxicillin but there were 41
hospitalizations. We have to consider that any hospitalization was due to
an adverse effect of amoxicillin because an adverse effect wich leads to
hospitalization must be considered as serious (4).
1.- ISCAP Study Group. Three day versus five day treatment with
amoxicillin for non-severe pneumonia in young children: a multicentre
randomised controlled trial. BMJ,
doi:10.1136/bmj.38049.490255.DE(published 30 March 2004).
2.- Margolis P, Gadomski A. Does this infant have pneumonia?. JAMA
1998; 279: 308-13.
3.- British Thoracic Society Standards of Care Committee. British
Thoracic Society Guidelines for the management of community acquired
pneumonia in chilhood. Thorax 2002; 57 (Suppl 1): 1-24.
4.- CIOMS Current challenges in pharmacovigilance: Pragmatic
approaches: Report of CIOMS Working Group V. Geneva: Council for
International Organisations of Medical Sciences. 2001.
Competing interests:
None declared
Competing interests: No competing interests
Sirs,
A part from the fact that amoxicillin is, in my clinical 46-year-long
experience, an efficacious antibiotic, but against Gram-positive bacteria,
(Haemophilus influenzae were isolated from the nasopharynx in 89.9%!), and
that can cause allergic side-effects, I can’t agree at all with the
conclusion of ISCAP study group, aiming to assess the efficacy of three
days versus five days of treatment with oral amoxicillin for curing non-
severe pneumonia in children. (1). As a matter of fact, in every day
practice doctor meet “single” patient, whose treatment must be performed
in a characteristic, personalized way, based not only on EBM and “large”
number Medicine, but also, and particularly, on Single Patient Based
Medicine (2, 3, 4) (See HONCode website 233736,
www.semeioticabiofisica.it, Biophysical Constitutions. SPBM). As regards
the days of treatment, from the SPBM view-point, doctor has to withdraw
the administered antibiotic only when “all” biophysical signs of
inflammation have disappeared completely: Acute Phase Protein synthesis,
Acute Antibody Synthesis syndrome, Reticulo-Endothelial-Hyperproduction
Syndrome, typical finger-pulp diagram of tissue microvascular-unit, and so
on, which allow doctor to conduct bed-side an objective therapeutic
monitoring (See the above-cited website). Unfortunately, all around the
world, machine-dependent physicians, including ISCAP Researchers, ignore
or overlook both Biophysical Semeiotics and the thousend suns, shining
above the clouds.
1) ISCAP Study Group. Three day versus five day treatment with
amoxicillin for non-severe pneumonia in young children: a multicentre
randomised controlled trial. BMJ 2004;328:791 (3 April),
doi:10.1136/bmj.38049.490255.DE (published 16 March 2004)
2) Sergio Stagnaro “Single Patient Based Medicine” versus EBM. (16
May 2003) BMJ.com http://bmj.com/cgi/eletters/326/7398/1048#32299
3) Sergio Stagnaro Biophysical Semeiotics, EBM, and SPBM useful in
treating children with soare throat. (5 December 2003) BMG.com.
http://bmj.bmjjournals.com/cgi/eletters/327/7427/1324
4) Stagnaro-Neri Marina, Stagnaro Sergio. "Introduzione alla Semeiotica
Biofisica. Il Terreno Oncologico". Travel Factory Edizioni, Roma, in
press.
Competing interests:
None declared
Competing interests: No competing interests
Stop Skimping, Start Investing
Some of the rapid responses following this article are particularly
illuminating and elicit appropriate caution in weighing the findings of
the study.
Specific limitations of the study which I would want to emphasise,
are these:
1.Given the prevalence of asthma, this exclusion from the study is
severely limiting. It is precisely in this area where many predictable
deaths may be found to reside. If the conclusion of the study was acted
upon, deaths amongst people suffering from undiagnosed asthma would be
likely.
2.The wrong comparison was used. The comparison should have been made
with more generous treatment as Borja pointed out in the rapid responses.
3.Caregivers’ assessments should not have been given such short-
thrift. How much suffering and incapacity did they report? How did their
weighting of disamenities differ from that of the researchers?
4.We are not told at what stage in the progression of the disease,
seriousness was assessed. This limits readers’ ability to evaluate the
accuracy of the assessment.
5.Treatment failure may have been underestimated. Treatment failure
markers were arguably not adequate. To adequately assess the danger to
which the children were exposed, oxygen saturation, for example, should
have been measured more regularly.
6.The costings are not generally applicable and do not take broader
social costs into account.
7.Most worringly, we are not given adequate mortality figures.
8.We should be worried about what happened to those who were not
cured at day 14.
This particular study relates to children living in India. It may be
considered in the broader perspectives of antibiotic policy and
respiratory medicine. Geographic, medical and social conditions are
relevant differentiating factors.
Roughly 54,000 people die in Britain each year from complications
related to respiratory infections. Some of these deaths are regarded as
merciful, but not everyone is in agreement.
Skimping on antibiotics is a contested tactic. In some contexts, the
false economy is highly dangerous. An example is where patients are
hospitalized, sometimes on life support, suffering from infections which
could have been managed less invasively with appropriate antibiotics.
Arguably, it is not as humane as sometimes believed. Furthermore, it fails
to grapple with the very real problem we face in the need for a new
generation of antibiotics.
No-one seriously doubts that antibiotics are at times, unnecessarily
prescribed. But the tokenism involved in inappropriate and dangerous
skimping is likely to give a false comfort which displaces and postpones
the need for real action on the antibiotic problem.
We really ought to take the responsibility for lobbying governments
to support research into developing new antibiotics and into imaginative
thinking in antiviral medicine. And yes, we probably do need some lateral
thinking about how we determine the legitimacy of medical evidence in
approving new drugs, if the necessary pharmaceutical developments for the
future are going to be viable. Adjunct changes in public policy are also
necessary.
Sacrificing people in the name of the species when the real reason is
poor economics, is no longer politically credible. We ought to be
particularly sensitive, when it is a vulnerable group, such as children
who called upon to make the sacrifice.
Competing interests:
Public health research in Children's Policy and Practice.
Competing interests: No competing interests