BMJ 2017;358:j4170 doi: 10.1136/bmj.
j4170 (Published 2017 September 22)
Editorials
Should we abandon “finishing the course” of
antimicrobials?
It depends on the type of infection
1 2
Chris Del Mar professor of public health , David F M Looke infectious disease physician
1
Bond University, Gold Coast, Australia; 2Princess Alexandra Hospital, University of Queensland, Brisbane, Queensland, Australia
The recent controversial article in The BMJ1 wasn’t the first
commentary to suggest that we should abandon the notion of a
course of antibiotics and rethink the whole strategy of duration
of therapy for infections.2 The objectives of treatment go beyond
“cure” (kill the pathogen) to include reducing symptom severity
and duration, the chances of relapse, and transmission to other
people. This can be achieved by suppressing the growth of the
pathogen until the host immune system destroys it.
How the concept of “the course” evolved is not entirely clear,2
but two strategies probably underlie it. These are to ensure a
total adequate dose by spreading a potentially toxic drug over
time to avoid high peak levels, and to reduce the chance of
resistance evolving within the patient during treatment. We
already have information about the duration of treatment needed
to get a high probability of cure for some infections. This ranges
from a single dose (eg, chlamydia, donovanosis, primary
syphilis) through a fixed and well tested duration (eg, malaria,
leprosy, tuberculosis) to lifelong suppressive therapy (eg, HIV
infection).
But the focus of this recent interest is on more common
indications for antibiotics.1 Adoption of shortened antibiotic
treatment periods has been happening for decades. In 1967 The
BMJ published a trial comparing a single dose of a long acting
sulphonamide (sulphormethoxine) for uncomplicated urinary
tract infection with a conventional course of five days of
ampicillin, finding similar cure rates with fewer adverse effects
in the sulphonamide group.3 Later trials using shorter courses
of the same antibiotic reached similar conclusions.4 A systematic
review of many other common infections, including acute
respiratory and urinary infections found that, in general, shorter
treatments of antibiotics were as effective as longer.5
Meningococcal disease, can be successfully treated with three
days of antibiotics6—or even one day, as has been shown in
Africa.7
The classical pharmacomicrobiological approach is to decide
which antibiotic to use, at what dose, and for how long after a
careful assessment of the pathogen (and the strain’s susceptibility
to the choice of antibiotics available), the antibiotic (its
Correspondence to: C Del Mar cdelmar@bond.edu.au
For personal use only: See rights and reprints http://www.bmj.com/permissions
Page 1 of 2
EDITORIALS
pharmacokinetics and pharmacodynamics), and the patient
(whether there is immune suppression, for example). Then each
of the options for dose and duration should be supported by
evidence of effectiveness.
Pragmatic prescribing
In practice, however, decisions must be made in the absence of
some, often most, of this information, especially in primary
care, where the basic research is missing. Even well known
guidance for treating streptococcal pharyngitis in vulnerable
populations to prevent acute rheumatic fever, which mandates
a 10 days of oral penicillin as firstline treatment,8 is extrapolated
from strategies found effective in historical randomised
controlled trials testing intramuscular penicillin over five days.8
Antibiotics are most commonly used for acute respiratory
infection in the community, where there is now good evidence
that the benefits overall, if any, are marginal, even for infections
that were traditionally treated almost routinely with antibiotics,
such as acute otitis media, acute cough, and sore throat.
Perhaps shorter courses are commonly found to be as effective
as longer ones because antibiotics are largely ineffective at any
dose. For example, comparing antibiotics with placebo for acute
otitis media in children, if the overall risk ratio for ear pain at
2-3 days has a number needed to treat (NNT) of 15-20 (meaning
that 15 to 20 children must be treated for one to have a day less
of pain), a trial would have to be very large to show a difference
between a standard and a shorter course of antibiotics. Moreover,
general practices that are parsimonious with antibiotics are not
exposing their patients to unacceptable risks of serious infections
such as bacterial meningitis mastoiditis or community acquired
pneumonia compared with liberal practices.9
What does all this mean for practicing clinicians? Should we
be rushing to rewrite guidelines and tell patients to be cavalier
about not finishing their courses of antibiotics? For serious
infections with sufficient evidence to inform the best duration
of antibiotic use, no. But for infections in which the use of
antibiotics is discretionary anyway, yes, perhaps we should tell
patients that they can stop their antibiotics when they feel
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BMJ 2017;358:j4170 doi: 10.1136/bmj.j4170 (Published 2017 September 22)
better—with the usual advice about returning for reassessment
if recovery does not go according to plan.
One major caveat concerns the fate of unused antibiotics. If
these are used improperly, taken for new infections without
indication, or given to other family members, for example, then
pragmatic advice to “stop when you feel better” could encourage
antibiotic resistance—the opposite of what was intended.
For researchers, the message is clearer. We still need more
randomised trials and their systematic reviews to establish the
optimal length of antibiotic use for many common infections,
with resistance included as an outcome measure.10 And we need
more studies of diagnostic aids and their systematic reviews to
establish when to stop (thereby shortening courses by several
days)—as well as when to start—antibiotics for specific
diagnoses.11
Competing interests: We have read and understood BMJ policy on
declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer
reviewed.
1 Llewelyn MJ, Fitzpatrick JM, Darwin E, et al. The antibiotic course has had its day. BMJ
2017;358:j3418. doi:10.1136/bmj.j3418 pmid:28747365.
2 Lambert HP. Don’t keep taking the tablets?Lancet 1999;358:943-5. doi:10.1016/S0140-
6736(99)01139-3 pmid:10489971.
For personal use only: See rights and reprints http://www.bmj.com/permissions
Page 2 of 2
EDITORIALS
3 Grüneberg RN, Brumfitt W. Single-dose treatment of acute urinary tract infection: a
controlled trial. Br Med J 1967;358:649-51. doi:10.1136/bmj.3.5566.649 pmid:6038338.
4 Fang LST, Tolkoff-Rubin NE, Rubin RH. Efficacy of single-dose and conventional
amoxicillin therapy in urinary-tract infection localized by the antibody-coated bacteria
technic. N Engl J Med 1978;358:413-6. doi:10.1056/NEJM197802232980802 pmid:340949.
5 Dawson-Hahn EE, Mickan S, Onakpoya I, et al. Short-course versus long-course oral
antibiotic treatment for infections treated in outpatient settings: a review of systematic
reviews. Fam Pract 2017 [Epub ahead of print.] doi:10.1093/fampra/cmx037 pmid:
28486675.
6 Ellis-Pegler R, Galler L, Roberts S, Thomas M, Woodhouse A. Three days of intravenous
benzyl penicillin treatment of meningococcal disease in adults. Clin Infect Dis
2003;358:658-62. doi:10.1086/377203 pmid:12942396.
7 Martin E, Hohl P, Guggi T, Kayser FH, Fernex M. Short course single daily ceftriaxone
monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter
study. Part I: Clinical results. Infection 1990;358:70-7. doi:10.1007/BF01641418 pmid:
2185156.
8 Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis
and treatment of acute Streptococcal pharyngitis: a scientific statement from the American
Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of
the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on
Functional Genomics and Translational Biology, and the Interdisciplinary Council on
Quality of Care and Outcomes Research: endorsed by the American Academy of
Pediatrics. Circulation 2009;358:1541-51. doi:10.1161/CIRCULATIONAHA.109.
191959 pmid:19246689.
9 Gulliford MC, Moore MV, Little P, et al. Safety of reduced antibiotic prescribing for self
limiting respiratory tract infections in primary care: cohort study using electronic health
records. BMJ 2016;358:i3410. doi:10.1136/bmj.i3410 pmid:27378578.
10 Leibovici L, Paul M, Garner P, et al. Addressing resistance to antibiotics in systematic
reviews of antibiotic interventions. J Antimicrob Chemother 2016;358:2367-9. doi:10.1093/
jac/dkw135 pmid:27169438.
11 Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics
in acute respiratory tract infections. Cochrane Database Syst Rev (forthcoming)
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