Perspectives

Knowing when to stop antibiotic therapy

Empirical antibiotic therapy that turns out
to be unnecessary, on review, can (and
should) be stopped immediately
fter 50 years of widespread antibiotic use,

A we have reached the point where experts are

seriously predicting “a postantibiotic era” and
the World Health Organization has declared antibiotic
resistance “a threat to global security”.1 No one can
doubt the enormous benefits of antibiotics in curing
or preventing serious sequelae of infections that were
once the main causes of death and chronic illness,
and enabling modern medical therapies that involve
significant immune suppression.
These benefits are dramatic, and toxic side effects are
apparently few. This makes it tempting — even now,
when we know the risks — to prescribe antibiotics
empirically at the first hint of infection, even viral
infection,2 lest it progress to serious sepsis (and
potential medicolegal or professional embarrassment3).
estimated to cost the United States health system
Although unnecessary antibiotic use is sometimes
US$21–34 billion per annum;1 and
driven by patients’ expectations, they can be modified
by public education.4 • all antibiotics have some specific adverse side
effects such as allergy (or, rarely, anaphylaxis) or
During the first 30 years of the antibiotic era, the dose-related haematological, gastrointestinal, renal
release of each new antibiotic was almost always or hepatic toxicity.
followed by the emergence of resistance in some Surveys of antibiotic use in hospital and community
previously susceptible bacteria, but there were always settings show that a third to a half of all prescriptions
new antibiotics in the pipeline, until recently. Now the are discordant with widely available antibiotic
pipeline has dried up and the incidence and spectrum guidelines.7,8 Individual decisions to prescribe are
of resistance among most common pathogens have often driven by the prescriber’s experience, confidence
reached alarming levels.1 How have we come to this and tolerance of risk, rather than by objective clinical
point, and what can we do to avoid the “end of the indications.2 Antimicrobial stewardship programs
antibiotic era”? are designed to support and share responsibility for
logical, evidence-based antibiotic prescribing decisions
in the context of inevitable clinical uncertainty,
How can we improve our use of antibiotics? and they can reduce unnecessary — and overall —
antibiotic use, without adverse patient outcomes.9,10
We still argue about how to optimise antibiotic use, but
there are some (more or less) undisputed facts:
“There is a common misconception that
• the incidence of antibiotic resistance is, broadly,
resistance will emerge if a prescribed
proportional to the total amount of antibiotics
used,5 notwithstanding many confounding antibiotic course is not completed”
variables;
In seriously ill patients with suspected bacterial sepsis,
• individual antibiotic exposure rapidly alters initial empirical therapy often means high-dose,
normal gut microflora, which can take months to broad-spectrum “cover”, justified by evidence that the
recover, risking overgrowth or acquisition of (and, mortality increases rapidly with every hour’s delay in
potentially, infection with) multiresistant bacteria, Gwendolyn L Gilbert
starting effective therapy.11 For example, recommended
MD, FRACP, MBioethics
Clostridium difficile or yeasts and spread to hospital, empirical therapy for patients with neutropenia who
household or nursing home contacts6 — and the Marie Bashir Institute for develop fever is to give piperacillin–tazobactam or
broader the spectrum and the longer the course, the Infectious Diseases and
Biosecurity, University of a fourth-generation cephalosporin.12 The need for
greater the risk; Sydney, Sydney, NSW. immediate, effective therapy in severe sepsis is often
• infections with antibiotic-resistant bacteria are lyn.gilbert@ extrapolated to milder (suspected) infections, with
sydney.edu.au
more difficult to treat and are associated with non-specific symptoms, for which therapy may not
higher mortality — antimicrobial resistance is be necessary or could be delayed until test results are
doi: 10.5694/mja14.01201 available to guide it.

MJA 202 (3) · 16 February 2015

121
Perspectives

Whether to treat and the appropriate choice of

evidence. However, for many syndromes associated
empirical therapy are not straightforward decisions,
with bacteraemia, there is no difference in outcome
even with the help of prescribing guidelines. However,
when shorter courses are used.13,14 In practice the
starting empirical therapy does not mean the patient
optimal duration of therapy depends on clinical
is committed to a fixed treatment course. Too often,
syndrome, the causative organism, whether source
initial therapy is continued without review, even
control is possible and the patient’s response to
when diagnostic tests indicate an alternative diagnosis therapy.14 For example, only 3–5 days of treatment is
(non-infective condition or viral infection) for which
needed for meningococcal meningitis, compared with
no antibiotic is needed or a narrower spectrum agent
10–14 days for pneumococcal meningitis.12 Additional
would suffice. For example, Streptococcus pneumoniae
studies are needed to validate shorter courses of
isolated from a blood culture from a patient with
antibiotic therapy for many other infections.
severe community-acquired pneumonia is an
indication to change from commonly prescribed Resistance is much more likely to occur with long
empirical therapy — ceftriaxone plus azithromycin — antibiotic courses, which are rarely indicated except
to benzylpenicillin alone.12 when the site of infection is relatively inaccessible
(in biofilm in sites such as a cardiac valve or foreign
body or in an abscess); these infections often cannot
Duration of treatment and resistance be cured without surgical removal of the source
or drainage of pus. There is no risk — and every
There is a common misconception that resistance advantage — in stopping a course of an antibiotic
will emerge if a prescribed antibiotic course is not immediately a bacterial infection has been excluded or
completed. Premature cessation of antibiotic therapy is unlikely; and minimal risk if signs and symptoms
will not increase the risk that resistance will emerge. of a mild infection have resolved.
For most infections, the recommended duration of
therapy (5–14 days, depending on syndrome) is Competing interests: No relevant disclosures.
based on expert opinion and convention, rather than Provenance: Commissioned; externally peer reviewed. 
solid
122 MJA 202 (3) · 16 February 2015
 Perspectives

1 World Health Organization. Antimicrobial resistance: global 7 Zarb P, Amadeo B, Muller A, et al. Identification of targets
report on surveillance 2014. Geneva: WHO, 2014. http://www. for quality improvement in antimicrobial prescribing: the
who.int/drugresistance/documents/surveillancereport/en web-based ESAC Point Prevalence Survey 2009. J
(accessed Oct 2014). Antimicrob Chemother 2011; 66: 443-449.
2 Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for 8 Stuart RL, Wilson J, Bellaard-Smith E, et al. Antibiotic use and
adults with colds, upper respiratory tract infections, and misuse in residential aged care facilities. Intern Med J 2012;
bronchitis by ambulatory care physicians. JAMA 1997; 278: 42: 1145-1149.
901-904. 9 McGowan JE. Antimicrobial stewardship – the state of the
3 Broom A, Broom J, Kirby E. Cultures of resistance? A art in 2011: focus on outcome and methods. Infect Control
Bourdieusian analysis of doctors’ antibiotic prescribing. Soc Hosp Epidemiol 2012; 33: 331-337.
Sci Med 2014; 110: 81-88. 10 Davey P, Brown E, Charani E, et al. Interventions to improve
4 Wutzke SE, Artist MA, Kehoe LA, et al. Evaluation of a national antibiotic prescribing practices for hospital inpatients.
programme to reduce inappropriate use of antibiotics for Cochrane Database Syst Rev 2013; (4): CD003543.
upper respiratory tract infections: effects on consumer 11 Kumar A, Roberts D, Wood KE, et al. Duration of hypotension
awareness, beliefs, attitudes and behaviour in Australia. before initiation of effective antimicrobial therapy is the
Health Promot Int 2007; 22: 53-64. critical determinant of survival in human septic shock. Crit
5 Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Care Med 2006; 34: 1589-1596.
Project Group. Outpatient antibiotic use in Europe and 12 Antibiotic Expert Groups. Therapeutic guidelines: antibiotic.
association with resistance: a cross-national database study. Version 14. Melbourne: Therapeutic Guidelines Limited, 2010.
Lancet 2005; 365: 579-587. 13 Havey TC, Fowler RA, Daneman N. Duration of antibiotic
6 Filius PM, Gyssens IC, Kershof IM, et al. Colonization and therapy for bacteremia: a systematic review and meta-
resistance dynamics of gram-negative bacteria in patients analysis. Crit Care 2011; 15: R267.
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