ArticlePDF Available

The antibiotic course has had its day

Authors:
The antibiotic course has had its day
With little evidence that failing to complete a prescribed antibiotic course contributes to antibiotic
resistance, it’s time for policy makers, educators, and doctors to drop this message, argue Martin
Llewelyn and colleagues
Martin J Llewelyn professor of infectious diseases 1 2, Jennifer M Fitzpatrick specialist registrar in
infection 2, Elizabeth Darwin project manager 3, SarahTonkin-Crine health psychologist 4, Cliff Gorton
retired building surveyor 5, John Paul consultant in microbiology 6, Tim E A Peto professor of infectious
diseases 7, Lucy Yardley professor of health psychology 8, Susan Hopkins consultant in infectious
diseases and microbiology 9, Ann Sarah Walker professor of medical statistics and epidemiology 3
1Department of Global Health and Infection, Brighton and Sussex Medical School, Falmer, BN1 9PS, UK; 2Department of Microbiology and Infection,
Brighton and Sussex University Hospitals NHS Trust, Brighton, UK ; 3Nuffield Department of Medicine, University of Oxford, UK; 4Nuffield Department
of Primary Care Health Sciences, Oxford, UK; 5Oxford, UK; 6Public Health England, Royal Sussex County Hospital, Brighton, UK; 7Oxford Biomedical
Research Centre, Oxford, UK; 8Faculty of Human and Social Sciences, University of Southampton, UK ; 9Royal Free London NHS Foundation Trust,
London, UK ; Correspondence to: M Llewelyn M.J.Llewelyn@bsms.ac.uk
Antibiotics are vital to modern medicine and antibiotic resistance
is a global, urgent threat to human health. The relation between
antibiotic exposure and antibiotic resistance is unambiguous
both at the population level1 and in individual patients.2
Reducing unnecessary antibiotic use is therefore essential to
mitigate antibiotic resistance.
Avoiding overuse requires healthcare professionals and the
public to be well informed about antibiotic treatment, as set out
in the first objective of the World Health Organization Global
Action Plan.3 Public communication about antibiotics often
emphasises that patients who fail to complete prescribed
antibiotic courses put themselves and others at risk of antibiotic
resistance. For example, in materials supporting Antibiotic
Awareness Week 2016 WHO advised patients to always
complete the full prescription, even if you feel better, because
stopping treatment early promotes the growth of drug-resistant
bacteria.4 Similar advice appears in national campaigns in
Australia,5 Canada,6 the United States,7and Europe.8 And in the
United Kingdom it is included as fact in the curriculum for
secondary school children.9
However, the idea that stopping antibiotic treatment early
encourages antibiotic resistance is not supported by evidence,
while taking antibiotics for longer than necessary increases the
risk of resistance. Without explicitly contradicting previous
advice, current public information materials from the US Centers
for Disease Control and Prevention (CDC) and Public Health
England have replaced complete the course with messages
advocating taking antibiotics exactly as prescribed.10 11 We
explore the evidence for antibiotic duration, clinical
effectiveness, and resistance, and encourage policy makers,
educators, and doctors to stop advocating complete the course
when communicating with the public. Further, they should
publicly and actively state that this was not evidence-based and
is incorrect.
Origins of the idea
Concern that giving too little antibiotic treatment could select
for antibiotic resistance can be traced back to the dawn of the
antibiotic era. When Howard Floreys team treated Albert
Alexanders staphylococcal sepsis with penicillin in 1941 they
eked out all the penicillin they had (around 4 g, less than one
days worth with modern dosing) over four days by repeatedly
recovering the drug from his urine. When the drug ran out, the
clinical improvement they had noted reversed and he
subsequently succumbed to his infection.12 There was no
evidence that this was because of resistance, but the experience
may have planted the idea that prolonged therapy was needed
to avoid treatment failure.
Flemings early work showed that sensitive bacteria could be
acclimatised to penicillin in the laboratory.13 In his 1945 Nobel
prize acceptance speech, Fleming painted a vivid clinical
vignette in which an imagined patient with a streptococcal throat
infection who takes insufficient penicillin, transmits the
infectionnow in resistant formto his wife, and is thus
responsible for her subsequent death from antibiotic resistant
disease.14 Fleming advised, If you use penicillin, use enough!
Ironically, Streptococcus pyogenes has never developed
resistance to penicillin, and we now know that for most forms
of antibiotic resistance that currently threaten patients, selection
of resistance in the bacteria being treated is of limited
importance.
Antibiotic treatment drives resistance
The scenario envisaged by Fleming was of target selected
resistance (box 1). Infections typically begin when a small
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2017;358:j3418 doi: 10.1136/bmj.j3418 (Published 2017 July 24) Page 1 of 5
Analysis
ANALYSIS
population of microorganisms gain access to the host and
replicate. Genetic mutations conferring antibiotic resistance
may arise spontaneously during replication and be selected for
during treatment. Target selected resistance can occur with
inadequate antimicrobial dosing or with monotherapy for
infections for which spontaneous resistant mutations arise on
treatment, such as tuberculosis, gonorrhoea, and HIV.
Early trials of tuberculosis treatment showed resistance emerging
during monotherapy15 and underpin the need for combination
therapy for this disease. Transmission of such pathogens during
or following inadequate treatment may allow resistant strains
to spread from person to person.
However, most of the bacterial species now posing the greatest
problems do not develop resistance through target selection.
The clinical threat comes mainly from species such as
Escherichia coli and the so called ESKAPE organisms
(Enterococcus faecium, Staphylococcus aureus, Klebsiella
pneumoniae, Acinetobacter spp, Pseudomonas spp, Enterobacter
spp), which are all found harmlessly in us, on us, or in our
environment. They can also act as opportunistic pathogens.
When a patient takes antibiotics for any reason, antibiotic
sensitive species and strains present among commensal flora
on their skin or gut or in the environment are replaced by
resistant species and strains ready to cause infection in the
future.16 This collateral selection (box 1) is the predominant
driver of the important forms of antibiotic resistance affecting
patients today. The longer the antibiotic exposure these
opportunist bacteria are subjected to, the greater the pressure to
select for antibiotic resistance.2 17
Importantly for these opportunistic pathogens, resistant strains
are transmitted between asymptomatic carriers rather than people
with disease. Furthermore, many resistance conferring genes
can pass easily between bacterial strains or species. Thus
antibiotic selection may drive outbreaks of resistant infections
independently of transmission of a specific strain or species.18
From fear of undertreatment to harm from
overtreatment
Traditionally, antibiotics are prescribed for recommended
durations or courses. Fundamental to the concept of an antibiotic
course is the notion that shorter treatment will be inferior. There
is, however, little evidence that currently recommended
durations are minimums, below which patients will be at
increased risk of treatment failure.
Historically, antibiotic courses were set by precedent, driven
by fear of undertreatment, with less concern about overuse. For
many indications, recommended durations have decreased as
evidence of similar clinical outcomes with shorter courses has
been generated (table 1). However, the picture is patchy and
complicated by comparisons of new and established agents that
may have different pharmacological properties (eg, long acting
macrolides versus short acting penicillins).
For most indications, studies to identify the minimum effective
treatment duration simply have not been performed.28 For
example, pyelonephritis has historically been treated for two
weeks. Trials have shown that shorter courses of quinolones are
effective (seven days for ciprofloxacin23 and five days for
levofloxacin24), but no such data exist for β-lactams, which are
the main antibiotic class used. Current international guidelines
recommend 10-14 days treatment with β-lactams, based purely
on absence of data for shorter courses.29
Shorter duration of treatment has been shown to reduce clinical
efficacy in a few cases. A notable example is otitis media, where
five days treatment is associated with a lower clinical cure rate
(66%) than 10 days (84%) in children under 2 years.19 Even in
this situation though, differences relate to prolongation of
symptoms not treatment failure, disease recurrence, or selection
for resistant pathogens.
For the opportunist pathogens for which antimicrobial resistance
poses the greatest threat, no clinical trials have shown increased
risk of resistance among patients taking shorter treatments.
The key argument for changing how we discuss antibiotic
courses with patients is that shorter treatment is clearly better
for individual patients. Not only does an individual patients
risk of resistant infection depend on their previous antibiotic
exposure2 17 but reducing that exposure by shorter treatment is
associated with reduced risk of resistant infection and better
clinical outcome. In hospital acquired pneumonia, for example,
randomised controlled trial data indicate that short treatment
strategies have equivalent clinical outcomes to longer courses
and are associated with lower rates of infection recurrence and
antibiotic resistance.25 26
Is the concept of an antibiotic course still
valid?
The concept of an antibiotic course ignores the fact that patients
may respond differently to the same antibiotic, depending on
diverse patient and disease factors. Currently, we largely ignore
this fact and instead make indication specific recommendations
for antibiotic duration that are based on poor evidence. This
situation is changing in hospital practice, where biomarkers of
treatment response such as procalcitonin can guide when to stop
antibiotic treatment.30 Outside hospital, where repeated testing
may not be feasible, patients might be best advised to stop
treatment when they feel better, in direct contradiction of WHO
advice.4 Of note, a recent clinical trial found that using fever
resolution to guide stopping antibiotics in community acquired
pneumonia halved the average duration of antibiotic treatment
without affecting clinical success.21 Further similar studies are
needed.
Complete the course: a barrier to
antibiotic conservation
The fallacious belief that antibiotic courses should always be
completed to minimise resistance is likely to be an important
barrier to reducing unnecessary antibiotic use in clinical practice
and to developing evidence to guide optimal antibiotic use. The
idea is deeply embedded, and both doctors and patients currently
regard failure to complete a course of antibiotics as irresponsible
behaviour.31 32
In primary care, strategies have been developed to avoid
unnecessary antibiotic courses being startedfor example,
through enhanced communication training, point-of-care tests,
and use of delayed prescriptions.33-35 However in secondary care,
strategies to reduce overuse aim to change, or ideally stop,
antibiotics 48-72 hours after they are started, but these are
challenging to implement.36 Reasons for this include diagnostic
uncertainty and team behaviour, but patients and healthcare
professionals concerns about the risks of incomplete treatment
are likely to contribute. Designing trials of antibiotic sparing
treatment is notoriously difficult,37 particularly if participants
are invited to consent to receiving shortened antibiotic treatment
on the basis that this could reduce their risk of antibiotic
resistance, when they have been taught from school that it
increases this risk.
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2017;358:j3418 doi: 10.1136/bmj.j3418 (Published 2017 July 24) Page 2 of 5
ANALYSIS
Box 1: Selection of antibiotic resistance
Target selectionFor certain professional pathogens, such as Mycobacterium tuberculosis, spontaneous resistance conferring mutants
may be selected during treatment, can be transmitted before cure is achieved, or can re-emerge after treatment failure. Other professional
pathogens where this may apply include HIV, malaria, gonorrhoea, and Salmonella typhi
Collateral selectionMany bacterial species that live harmlessly in the gut, on our skin and mucus membranes, or in the environment can
also cause disease as opportunist pathogens. For such organisms, resistance selection occurs predominantly during antibiotic treatment of
other infections. Resistance in opportunists may be passed easily to other strains of the same species of bacteria or to different species.
Key examples include methicillin resistance in Staphylococcus aureus, extended spectrum β-lactamase producing Enterobacteriaceae and
carbapenem resistance in Klebsiella pneumoniae
What should we advise patients?
The complete the course message has persisted despite not
being supported by evidence and previous arguments that it
should be replaced.18 38 One reason it may be so resilient is that
it is simple and unambiguous, and the behaviour it advocates
is clearly defined and easy to carry out. Nevertheless, there is
evidence that, in many situations, stopping antibiotics sooner
is a safe and effective way to reduce antibiotic overuse. Daily
review of the continued need for antibiotics is a cornerstone of
antibiotic stewardship in hospitals,39 but in primary care, where
85% of antibiotic prescriptions are written, no such ongoing
assessment is attempted.
There are reasons to be optimistic that the public will accept
that completing the course to prevent resistance is wrong if the
medical profession openly acknowledges that this is so, rather
than simply substituting subtle alternatives such as exactly as
prescribed. Completing the course goes against one of the most
fundamental and widespread medication beliefs people have,
which is that we should take as little medication as necessary.40
Concerted and consistent efforts have successfully educated the
public that antibiotics do not treat viral infections, for example.
Research is needed to determine the most appropriate simple
alternative messages, such as stop when you feel better. Until
then, public education about antibiotics should highlight the
fact that antibiotic resistance is primarily the result of antibiotic
overuse and is not prevented by completing a course. The public
should be encouraged to recognise that antibiotics are a precious
and finite natural resource that should be conserved. This will
allow patient centred decision making about antibiotic treatment,
where patients and doctors can balance confidence that a
complete and lasting cure will be achieved against a desire to
minimise antibiotic exposure unimpeded by the spurious concern
that shorter treatment will cause antibiotic resistance.
Contributors and sources: LY, MJL, TEAP, SH, and ASW are
investigators on an on an NIHR Programme Grant for Applied Research
(PGfAR) called ARK-hospital, which aims to reduce antibiotic overuse
in hospitals through clinical review of antibiotic prescriptions
[RP-PG-0514-20015]. ASW, STC, TEAP, and SH are investigators in
the NIHR Health Protection Research Unit (NIHR HPRU) in healthcare
associated infections and antimicrobial resistance at Oxford University
in partnership with Public Health England (PHE) [grant
HPRU-2012-10041]. CG is a retired building surveyor. ED is a project
manager for ARK and the HPRU. JP is Public Health England regional
microbiologist for the south east. The article is based on published good
quality randomised clinical trials and observational cohort studies. All
authors have contributed to this paper and concur on its content. MJL
is guarantor. The views expressed in this publication are those of the
authors and not necessarily those of their employers.
Competing interests: We have read and understood BMJ policy on
declaration of interests and have no relevant interests to declare.
1Goossens H, Ferech M, Vander Stichele R, Elseviers M. ESAC Project Group. Outpatient
antibiotic use in Europe and association with resistance: a cross-national database study.
Lancet 2005;365:579-87. doi:10.1016/S0140-6736(05)70799-6 pmid:15708101.
2 Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in
primary care on antimicrobial resistance in individual patients: systematic review and
meta-analysis. BMJ 2010;340:c2096. doi:10.1136/bmj.c2096. pmid:20483949.
3 World Health Organization. Global action plan on antimicrobial resistance 2015.http://
www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf
4World Health Organization. How to stop antibiotic resistance? Heres a WHO prescription.
2015. http://www.who.int/mediacentre/commentaries/stop-antibiotic-resistance/en/
5 NPS Medicinewise. Antibiotic resistance: the facts. https://www.nps.org.au/medical-info/
consumer-info/antibiotic-resistance-the-facts
6 National Collaborating Centre for Infectious Diseases. Antibiotic use and resistance:
information for patients. https://nccid.ca/antibiotic-awareness/
7 Federal Drugs Administration. Combatting antibiotic resistance. Follow directions for
proper use. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm092810.htm#
follow
8 European Antibiotic Awareness Day. Factsheet for general public. http://ecdc.europa.eu/
en/eaad/antibiotics-get-informed/Pages/get-informed.aspx
9 Assessment and Qualifications Alliance. GCSE biology specification. http://www.aqa.org.
uk/subjects/science/gcse/biology-8461
10 Centers for Disease Control. Get smart about antibiotics. What you can do. https://www.
cdc.gov/getsmart/community/about/can-do.html
11 UK Government. Antibiotic awareness resources 2016. https://www.gov.uk/government/
collections/european-antibiotic-awareness-day-resources
12 Abraham EP, Chain E, Fletcher CM, et al. Further observations on penicillin. Lancet
1941;238:177-89doi:10.1016/S0140-6736(00)72122-2.
13 Fleming A. On the antibacterial action of cultures of a penicillium, with special reference
to their use in the isolation of B. influenzae. Br J Exp Pathol 1929;10:226-36.
14 Fleming A. Penicillin. Nobel lecture, 11 Dec 1945.https://www.nobelprize.org/nobel_prizes/
medicine/laureates/1945/fleming-lecture.pdf
15 Medical Research Countil. Streptomycin treatment of pulmonary tuberculosis. Br Med J
1948;2:769-82. doi:10.1136/bmj.2.4582.769 pmid:18890300.
16 Crémieux A-C, Muller-Serieys C, Panhard X, et al. Emergence of resistance in normal
human aerobic commensal flora during telithromycin and amoxicillin-clavulanic acid
treatments. Antimicrob Agents Chemother 2003;47:2030-5. doi:10.1128/AAC.47.6.2030-
2035.2003 pmid:12760893.
17 Lodise TP, Miller CD, Graves J, et al. Clinical prediction tool to identify patients with
Pseudomonas aeruginosa respiratory tract infections at greatest risk for multidrug
resistance. Antimicrob Agents Chemother 2007;51:417-22. doi:10.1128/AAC.00851-
06 pmid:17158943.
18 Sheppard AE, Stoesser N, Wilson DJ, et al. Modernising Medical Microbiology (MMM)
Informatics Group. Nested Russian doll-like genetic mobility drives rapid dissemination
of the carbapenem resistance gene blaKPC. Antimicrob Agents Chemother
2016;60:3767-78. doi:10.1128/AAC.00464-16 pmid:27067320.
19 Hoberman A, Paradise JL, Rockette HE, et al. Shortened Antimicrobial Treatment for
Acute Otitis Media in Young Children. N Engl J Med 2016;375:2446-56. doi:10.1056/
NEJMoa1606043 pmid:28002709.
20 Altamimi S, Khalil A, Khalaiwi KA, Milner RA, Pusic MV, Al Othman MA. Short-term
late-generation antibiotics versus longer term penicillin for acute streptococcal pharyngitis
in children. Cochrane Database Syst Rev 2012;8:CD004872.pmid:22895944.
21 Uranga A, España PP, Bilbao A, et al. Duration of antibiotic treatment in
community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med
2016;176:1257-65. doi:10.1001/jamainternmed.2016.3633. pmid:27455166.
22 Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC.
Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated
cellulitis. Arch Intern Med 2004;164:1669-74. doi:10.1001/archinte.164.15.1669 pmid:
15302637.
23 Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in
women with acute pyelonephritis: a randomised, open-label and double-blind,
placebo-controlled, non-inferiority trial. Lancet 2012;380:484-90. doi:10.1016/S0140-6736(
12)60608-4 pmid:22726802.
24 Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized
comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg
twice-daily for 10 days for the treatment of complicated urinary tract infections and acute
pyelonephritis. Urology 2008;71:17-22. doi:10.1016/j.urology.2007.09.002pmid:18242357.
25 Chastre J, Wolff M, Fagon JY, et al. PneumA Trial Group. Comparison of 8 vs 15 days
of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial.
JAMA 2003;290:2588-98. doi:10.1001/jama.290.19.2588 pmid:14625336.
26 Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic
therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution
for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000;162:505-11.
doi:10.1164/ajrccm.162.2.9909095 pmid:10934078.
27 Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy
for intraabdominal infection. N Engl J Med 2015;372:1996-2005. doi:10.1056/
NEJMoa1411162 pmid:25992746.
28 Spellberg B. The new antibiotic mantra—“shorter is better. JAMA Intern Med
2016;176:1254-5. doi:10.1001/jamainternmed.2016.3646 pmid:27455385.
29 Gupta K, Hooton TM, Naber KG, et al. Infectious Diseases Society of America European
Society for Microbiology and Infectious Diseases. International clinical practice guidelines
for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010
update by the Infectious Diseases Society of America and the European Society for
Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20. doi:10.1093/cid/
ciq257 pmid:21292654.
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2017;358:j3418 doi: 10.1136/bmj.j3418 (Published 2017 July 24) Page 3 of 5
ANALYSIS
Key messages
Patients are put at unnecessary risk from antibiotic resistance when treatment is given for longer than necessary, not when it is stopped
early
For common bacterial infections no evidence exists that stopping antibiotic treatment early increases a patients risk of resistant infection
Antibiotics are a precious and finite natural resource which should be conserved by tailoring treatment duration for individual patients
Clinical trials are required to determine the most effective strategies for optimising duration of antibiotic treatment
30 Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic
therapy decisions: a systematic review of randomized controlled trials and
recommendations for clinical algorithms. Arch Intern Med 2011;171:1322-31. doi:10.1001/
archinternmed.2011.318 pmid:21824946.
31 Brookes-Howell L, Elwyn G, Hood K, et al. The body gets used to them: patients
interpretations of antibiotic resistance and the implications for containment strategies. J
Gen Intern Med 2012;27:766-72. doi:10.1007/s11606-011-1916-1 pmid:22065334.
32 McCullough AR, Parekh S, Rathbone J, Del Mar CB, Hoffmann TC. A systematic review
of the publics knowledge and beliefs about antibiotic resistance. J Antimicrob Chemother
2016;71:27-33. doi:10.1093/jac/dkv310 pmid:26459555.
33 Little P, Moore M, Kelly J, et al. PIPS Investigators. Delayed antibiotic prescribing strategies
for respiratory tract infections in primary care: pragmatic, factorial, randomised controlled
trial. BMJ 2014;348:g1606. doi:10.1136/bmj.g1606 pmid:24603565.
34 Little P, Stuart B, Francis N, et al. GRACE consortium. Effects of internet-based training
on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster,
randomised, factorial, controlled trial. Lancet 2013;382:1175-82. doi:10.1016/S0140-6736(
13)60994-0 pmid:23915885.
35 Butler CC, Simpson SA, Dunstan F, et al. Effectiveness of multifaceted educational
programme to reduce antibiotic dispensing in primary care: practice based randomised
controlled trial. BMJ 2012;344:d8173. doi:10.1136/bmj.d8173 pmid:22302780.
36 Llewelyn MJ, Hand K, Hopkins S, Walker AS. Antibiotic policies in acute English NHS
trusts: implementation of start smart-then focus and relationship with Clostridium difficile
infection rates. J Antimicrob Chemother 2015;70:1230-5.pmid:25538165.
37 Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices
for hospital inpatients. Cochrane Database Syst Rev 2013;4:CD003543.pmid:23633313.
38 Lambert HP. Dont keep taking the tablets?Lancet 1999;354:943-5. doi:10.1016/S0140-
6736(99)01139-3 pmid:10489971.
39 UK Government. Start smart then focus. Antimicrobial stewardship toolkit for English
hospitals. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-
smart-then-focus
40 Horne R, Chapman SC, Parham R, Freemantle N, Forbes A, Cooper V. Understanding
patients adherence-related beliefs about medicines prescribed for long-term conditions:
a meta-analytic review of the necessity-concerns framework. PLoS One 2013;8:e80633.
doi:10.1371/journal.pone.0080633 pmid:24312488.
Published by the BMJ Publishing Group Limited. For permission to use (where not already
granted under a licence) please go to http://group.bmj.com/group/rights-licensing/
permissions
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2017;358:j3418 doi: 10.1136/bmj.j3418 (Published 2017 July 24) Page 4 of 5
ANALYSIS
Table
Table 1| Indications for which duration of antibiotic treatment has been evaluated by randomised controlled trial
Evidence on resistanceMain evidenceNo of days treatmentIndication
EvaluatedStandard
Similar short term selection of resistance in
nasopharyngeal organisms
Clinical failure higher with 5 days than 10 days treatment (1 trial)510Otitis media19
Not assessedComparable effect of 3-6 days oral antibiotics to 10 days penicillin
in children with streptococcal throat infection (Cochrane review of
20 studies)
3-610Streptococcal pharyngitis20
Not assessed. β-lactam treatment >5 days
associated with greater carriage of resistant
S pneumoniae
Non-inferiority of 5 day course once afebrile and clinical stability
improving compared with physician guided therapy (median 10
days) for clinical success (1 trial)
57-10Community acquired
pneumonia21
Not assessedNon-inferiority of 5 day course compared with 10 days for clinical
resolution (1 trial)
57-14Cellulitis22
Not assessedNon-inferiority of 7 v 14 days ciprofloxacin for cure12 and 5 days
levofloxacin v 10 days ciprofloxacin for eradication of infection
and clinical cure13
5-714Pyelonephritis23 24
Lower risk of further or resistant infection in
patients receiving shorter duration therapy
Non-inferiority of short course treatment of suspected pneumonia
among critical care patients on ICU mortality and infection
recurrence (multiple trials)
7-810-15Nosocomial pneumonia25 26
Non-significantly lower rates of
extra-abdominal resistant infection in short
course group
Non-inferiority of fixed 4 day course compared with physician
guided therapy (median 8 days) for surgical site infection, recurrent
intraabdominal infection, or death (1 trial)
47-14Intra-abdominal sepsis27
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2017;358:j3418 doi: 10.1136/bmj.j3418 (Published 2017 July 24) Page 5 of 5
ANALYSIS
... The survey found that 61% of respondents preferred a 7-day course of antibiotics, while one-third preferred a 5-day course. This suggests that Lithuanian dentists may not fully adhere to recommendations for the shortest effective antimicrobial treatment duration [6,22]. Similar trends toward longer-course prescriptions have been observed in a few other countries as well [14,19]. ...
... Similar trends toward longer-course prescriptions have been observed in a few other countries as well [14,19]. The overuse of antibiotics is a major factor in resistance development, which correlates with exposure duration [22]. Furthermore, there is increasing evidence that the development of antibiotic resistance directly correlates with the duration of exposure [22]. ...
... The overuse of antibiotics is a major factor in resistance development, which correlates with exposure duration [22]. Furthermore, there is increasing evidence that the development of antibiotic resistance directly correlates with the duration of exposure [22]. Based on the present survey, endodontists and prosthodontists tend to prescribe antibiotics for a shorter period of time than other dentists. ...
Article
Full-text available
Background and Objectives: The inappropriate use of antibiotics can lead to antimicrobial resistance. Overprescribing in dental practice has been reported. This study aimed to describe patterns of antibiotic prescription for treating and preventing odontogenic infections based on reports from Lithuanian dentists. Materials and Methods: Questionnaires were sent to all 4751 Lithuanian dentists registered in the database of the Lithuanian Dental Chamber who had consented to participate in surveys. The questionnaire addressed antibiotic prescription preferences for the treatment and prevention of various dental pathologies. The statistical analysis included chi-square tests and a factor analysis to evaluate prescription frequences in different clinical scenarios considering the respondents’ specialty and age. Results: Of 647 responses, 497 were from general dentists, 35 from oral surgeons, 40 from endodontists, 20 from periodontists, and 35 from prosthodontists. Respondents were grouped by age: A (≤35 years, n = 207), B (36–50 years, n = 224), and C (≥51 years, n = 209). Amoxicillin was the first-choice antibiotic for 81.1% of respondents (group A more frequently than other groups, p = 0.001). A 7-day treatment duration was preferred by 60.8%, while 33.6% chose 5 days. For patients allergic to β-lactam antibiotics, 63% preferred clindamycin. Over 90% cited acute apical abscess with systematic involvement as an indication for antibiotic prescription. A factor analysis of 18 clinical scenarios revealed prescription differences among dental specialists, oral surgeons, and periodontists prescribing antibiotics more frequently than general dentists and endodontists. For prophylaxis, 87.5% recommended antibiotics for patients at risk of infectious endocarditis after a cardiologist’s consultation (group C less frequently than other groups, p = 0.021). Conclusions: Lithuanian dentists generally prefer narrow-spectrum antibiotics for the treatment of odontogenic infections. There are notable differences in prescription patterns among dental specialists, with younger dentists showing a trend towards more rational antibiotic use.
... The way pharmacists think about antibiotics is closely tied to how they dispatch them. Similarly, beliefs about how often antibiotics are used and when they should be prescribed for common illnesses show how attitudes affect prescription habits [28,29]. In the current study, statements emphasizing the importance of appropriate antibiotic dispensing were associated strongly with concerns about the spread of antibiotic resistance due to misuse (p = 0.000). ...
... Additionally, our data demonstrated that the caution against using unprescribed antibiotics aligns significantly with the risk of harm to patients and with antibiotic resistance (p = 0.044). In this context, not seeing an association between believing antibiotics can be harmful and understanding antibiotic resistance suggests that there may be a gap in understanding the bigger picture of antibiotic misuse [29]. Our results also suggest that there is a significant association between recognizing the issue of antibiotic overuse and the misconception about the effectiveness of antibiotics in viral infections to provide the patient with a faster recovery (p = 0.030). ...
Article
Full-text available
Introduction: The global healthcare system faced unparalleled challenges during the coronavirus disease 2019 (COVID-19) pandemic, potentially reshaping antibiotic usage trends. This study aimed to evaluate the knowledge, perceptions, and observations of community pharmacists concerning antibiotic utilization during and after the pandemic; and offer crucial insights into its impact on antibiotic usage patterns and infection dynamics. Methodology: This cross-sectional study involved 162 community pharmacists in Northern Cyprus. Data were gathered via a structured survey, including pharmacist demographics, antibiotic knowledge, perceptions of antibiotic resistance, and observations on antibiotic misuse during and after the COVID-19 pandemic. The data were analyzed by biostatistical methods. Results: Over 90% of pharmacists demonstrated high awareness of antibiotic overuse and resistance. The average antibiotic use knowledge score was 5.09/7. The majority expressed interest in further education (85.2%) and participation in campaigns (96.9%) to promote appropriate antibiotic use. Notably, 87.7% of participants observed an increase in respiratory infections post pandemic, and 45.7% reported administering more antibiotics, reflecting heightened demand. Furthermore, 63.6% noted increased demand for unprescribed antibiotics, while 45.7% expressed concerns about potential neglect of the antibiotic resistance issue as a consequence of the pandemic. Conclusions: The study highlights critical changes in antibiotic dispensing patterns among community pharmacists during and after the COVID-19 pandemic. The results here underscore the pivotal role of pharmacists in antibiotic stewardship, advocating for ongoing education, and stricter prescription regulations to optimize antibiotic use and combat resistance.
... The debate over whether to stop antibiotic treatment when symptoms improve is longstanding and controversial. While Llewelyn et al. (2017) question the necessity of completing antibiotic courses [48], the WHO and current clinical guidelines still emphasize that full adherence is crucial. Prematurely stopping antibiotics may contribute to the development of ABR [49]. ...
... The debate over whether to stop antibiotic treatment when symptoms improve is longstanding and controversial. While Llewelyn et al. (2017) question the necessity of completing antibiotic courses [48], the WHO and current clinical guidelines still emphasize that full adherence is crucial. Prematurely stopping antibiotics may contribute to the development of ABR [49]. ...
Article
Full-text available
Introduction: Self-medication with antibiotics (SMA)-the use of these drugs without a physician's diagnosis, supervision, or a medical prescription-has emerged as a significant crisis in many societies, being a particular concern in low-and middle-income countries. SMA practices hinder global efforts to reduce antibiotic consumption in the human health sector and to control antimicrobial resistance (AMR). The aims of the study were to explore the motivations, perspectives, and personal experiences of the Malaysian population related to SMA, analyzing their subjective viewpoints, attitudes, and behaviors. Methods: The present qualitative study applied an interpre-tivism paradigm to explore the complex topic of SMA; the interview questions were developed and confirmed by experts in AMR and pharmacy practice. Qualitative data analysis was carried out through a thematic approach. Results: Out of twenty-seven (n = 27) eligible individuals, eleven (n = 11) agreed to participate in in-depth interviews. Three main themes and seven subthemes were identified. Participants revealed directly purchasing antibiotics from pharmacies, due to doctors prescribing similar medications for comparable illnesses in the past. Trust issues related to physicians prescribing unnecessary additional medications and suspected personal motives were revealed. Budgetary constraints, timesaving, and aspects of self-care were identified as some of the key drivers for SMA. Conclusions: The current study's findings contribute to the understanding of the complexities surrounding SMA and provides insights into the public perceptions and behaviors regarding unregulated antibiotic use in Malaysia. Understanding these dynamics may inform targeted public health interventions to address SMA to mitigate the development of AMR.
... Traditionally, short-course antibiotic treatment has aroused concerns that insufficient durations could result in clinical failure, relapsing infection, and selection of resistance in the culprit pathogen. 4 The harms of excessive duration of treatment include avoidable adverse events, 5 Clostridioides difficile infection, 6 development of resistance among nontarget bacteria, and excess costs. ...
Article
Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain. Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus. The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points. Results: Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, -1.6 percentage points [95.7% confidence interval {CI}, -4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, -2.0 percentage points [95% CI, -4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics. Conclusions: Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.).
... Some factors are amenable to intervention, to minimize suboptimal antimicrobial use.With respect to personal and social factors, we found that 2 erroneous beliefs held by some veterinarians are a substantial barrier to AMS: that a predetermined duration of antimicrobial treatment must be completed; and that a longer duration of treatment decreases the risk of AMR because it is more likely to eliminate resistant pathogen subpopulations. Current evidence shows that shorter durations are generally as effective as longer durations, are less likely to cause adverse effects and less likely to select for AMR.29,30 Nevertheless, the "finish the course" mantra persists, leading to unnecessarily long durations of treatment and overuse of long-acting cefovecin injections. ...
Article
Full-text available
Background Minimizing harm from antimicrobials requires use of the narrowest spectrum drug, at an effective dose for the minimum effective duration. Many prescribers are not currently following these guidelines. To address suboptimal antimicrobial use, the underlying reasons must be understood. Objectives To identify factors influencing choices of antimicrobial drug, dose, and duration for companion animals. Subjects Twenty‐two veterinarians treating companion animals in Australia. Diversity of participants was deliberately sought. Methods Semistructured interviews were conducted online. Two case studies were discussed, and then a range of broader questions was posed. Transcripts were analyzed thematically, using an inductive approach. Results Few participants chose guideline‐concordant management for the case studies. Prescribing choices were influenced by a complex array of factors associated with the clinical case, pet owner, drug, veterinarian, veterinary colleagues, and external factors. Key factors driving broad‐spectrum antimicrobial use included a sense of safety, habit, ease of administering the drug (especially in cats), pharmaceutical marketing, and the self‐perpetuating dispensary cycle. Many participants were concerned about antimicrobial resistance, but insufficiently informed about how to minimize this risk. Several participants believed that longer duration of treatment and ensuring patients finish a predetermined course would decrease the risk of antimicrobial resistance and improve clinical outcomes. Conclusions and Clinical Importance Veterinarians are engaged with the concept of antimicrobial stewardship, but face numerous practical barriers and require more information. In particular, improved education is needed on enhancing patient safety by minimizing both spectrum of activity and duration of treatment, and dispelling myths about “finishing the course.”
Article
Purpose of review Optimal duration of therapy in SSTIs – a heterogeneous group of infections – remains unknown. The advances in knowledge of antibiotic duration of treatment in selected SSTIs that can impact clinical practice and published in the last 18 months are reviewed. Recent findings Recent evidence indicates that few patients receive guideline concordant empiric antibiotics and appropriate duration in the United States, although this likely can be extrapolated to other countries. One of the most commonly identified opportunities to improve antibiotic stewardship is duration of therapy more than 10 days. The long-standing debate regarding the significance of abscess size and its impact on clinical response to antibiotics, following proper drainage, is increasingly shifting towards the conclusion that abscess size is not directly associated with cure. In obese patients with SSTI, there is no benefit to longer antibiotic durations for SSTIs in patients with obesity, and it appears that longer antibiotic duration of therapy was associated with increased treatment failure. In diabetic foot infections (DFO), two randomized studies suggest that in the presence of osteomyelitis, the total duration of antibiotic therapy for patients treated nonsurgically does not need to be more than 6 weeks. In a prospective, randomized, noninferiority, pilot trial, patients with DFO who underwent surgical debridement and received either a 3-week or 6-week course of antibiotic therapy had similar outcomes and antibiotic-related adverse events. In patients with necrotizing soft tissue infections, successive observational studies clearly suggest that short duration of antibiotic treatment after NSTI source control is as well tolerated and effective as a longer course. It appears that 48 h would be enough. The possibility of fixed versus individualized approaches to therapy for common bacterial infections, including SSTIs merits to be considered seriously. Fully individualized therapy may be an ideal approach to maximize the benefits and minimize the harms of antimicrobials. Much more work is needed before this strategy becomes feasible. Summary There is increasing evidence that shorter duration of treatment is better in different types of SSTIs. Paradoxically, evaluation of real-life clinical practice indicates that long treatments continue to be commonly given to this population.
Article
Background Reducing antibiotic duration is a key stewardship intervention to mitigate antimicrobial resistance (AMR). We examined current evidence informing antibiotic duration for common bacterial infections to identify any gaps in terms of settings, patient populations and infectious conditions. Trial methodologies were assessed to identify areas for improvement. Methods MEDLINE and Embase were searched up to July 2024 for randomized trials comparing antibiotic durations in hospital and community settings (PROSPERO 2021, CRD42021276209). A narrative synthesis of the results was performed with a review on the major guidelines published by IDSA, NICE, WHO and other international societies to assess the impact of these trials on practice guidance. Results Out of 315 studies, 85% concluded equivalence or non-inferiority of shorter courses. Adult bacterial sinusitis, community-acquired pneumonia, female cystitis/pyelonephritis, uncomplicated cellulitis and intra-abdominal infection with adequate source control and perioperative prophylaxis had robust evidence supporting shorter durations. Few trials studied severe infections, such as bloodstream infections and ventilator-associated pneumonia. Twenty-three (7%) of the trials were conducted in intensive care settings and only 43 trials (14%) enrolled patients from low-to-middle- or low-income countries. Only 15% of studies were at low risk for bias. Conclusions Reducing antibiotic duration likely remains an important strategy for antibiotic stewardship, and an area of active research. While shorter antibiotic courses may be suitable for many bacterial infections, more evidence is needed for severe infections and in low- and middle-income settings.
Article
Antimicrobial resistance (AMR) is a threat to public health globally and is expected to worsen if not addressed. AMR has far-reaching consequences, impacting patients, public health, health-care systems, and society. It not only leads to increased morbidity and mortality but also poses significant challenges to the health-care industry, resulting in treatment failures and escalating costs associated with intensive interventions. Hospitals are also affected by AMR through prolonged hospital stays with increased costs of health care. It significantly impacts the success of cancer chemotherapy and organ transplantation and often compromises major surgeries. In this review, we have highlighted the clinical and economic consequences of AMR and the importance of antimicrobial stewardship programs (AMS programs) to combat resistance and protect patient health. As part of an organizational or system-wide health-care strategy, the AMS programs promote, evaluate, improve, and monitor the rational use of antimicrobials to safeguard their future effectiveness while promoting and protecting public health. We have also discussed the role of AMS programs in mitigating the clinical and economic impacts of AMR in Indian hospitals and provided some key suggestions for implementing AMS programs in this setting.
Article
Full-text available
Purpose Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown. The objective of this study was to evaluate the potential non-conformity of prescribed antibiotic pack sizes. Methods This retrospective observational study was based on claims data from a large Swiss health insurance company. The study analysed the prescriptions of eleven different antibiotic substances recommended for the five most common indications for antibiotics in Switzerland. All prescriptions for adult outpatients issued by general practitioners in 2022 were included and extrapolated to the entire Swiss population. Potential non-conformity was defined as a mismatch between the total dosage in a pack and the total dosage recommended. Results A total of n = 947,439 extrapolated prescriptions were analysed. In 10 of 23 of all analysed substance/indication combinations none of the prescribed packs aligned with the respective guideline recommendation. Considering pack sizes in which the total prescribed dosage of a substance did not correspond to any of the total dosages recommended in at least one of the guidelines, 31.6% of prescriptions were potentially non-conform and an estimated number of 2.7 million tablets were overprescribed. Conclusions We found a large discrepancy between prescribed pack sizes and guideline recommendations. Since inadequately prepacked antibiotics may lead to antibiotic resistance and unnecessary waste, efforts are needed to implement alternatives like exact pill dispensing.
Article
Full-text available
Background: high-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. Methods: after a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. Results: the baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42–0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54–0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36–0·74, p<0·0001; enhanced communication 0·68, 0·50–0·89, p=0·003; combined 0·38, 0·25–0·55, p<0·0001). Interpretation: internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries
Article
Full-text available
Background Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media. Methods We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin–clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms. Results Children who were treated with amoxicillin–clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001). Conclusions Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107.)
Article
Full-text available
Importance: The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) has not been well established. Objective: To validate Infectious Diseases Society of America/American Thoracic Society guidelines for duration of antibiotic treatment in hospitalized patients with CAP. Design, setting, and participants: This study was a multicenter, noninferiority randomized clinical trial performed at 4 teaching hospitals in Spain from January 1, 2012, through August 31, 2013. A total of 312 hospitalized patients diagnosed as having CAP were studied. Data analysis was performed from January 1, 2014, through February 28, 2015. Interventions: Patients were randomized at day 5 to an intervention or control group. Those in the intervention group were treated with antibiotics for a minimum of 5 days, and the antibiotic treatment was stopped at this point if their body temperature was 37.8°C or less for 48 hours and they had no more than 1 CAP-associated sign of clinical instability. Duration of antibiotic treatment in the control group was determined by physicians. Main outcomes and measures: Clinical success rate at days 10 and 30 since admission and CAP-related symptoms at days 5 and 10 measured with the 18-item CAP symptom questionnaire score range, 0-90; higher scores indicate more severe symptoms. Results: Of the 312 patients included, 150 and 162 were randomized to the control and intervention groups, respectively. The mean (SD) age of the patients was 66.2 (17.9) years and 64.7 (18.7) years in the control and intervention groups, respectively. There were 95 men (63.3%) and 55 women (36.7%) in the control group and 101 men (62.3%) and 61 women (37.7%) in the intervention group. In the intent-to-treat analysis, clinical success was 48.6% (71 of 150) in the control group and 56.3% (90 of 162) in the intervention group at day 10 (P = .18) and 88.6% (132 of 150) in the control group and 91.9% (147 of 162) in the intervention group at day 30 (P = .33). The mean (SD) CAP symptom questionnaire scores were 24.7 (11.4) vs 27.2 (12.5) at day 5 (P = .10) and 18.6 (9.0) vs 17.9 (7.6) at day 10 (P = .69). In the per-protocol analysis, clinical success was 50.4% (67 of 137) in the control group and 59.7% (86 of 146) in the intervention group at day 10 (P = .12) and 92.7% (126 of 137) in the control group and 94.4% (136 of 146) in the intervention group at day 30 (P = .54). The mean (SD) CAP symptom questionnaire scores were 24.3 (11.4) vs 26.6 (12.1) at day 5 (P = .16) and 18.1 (8.5) vs 17.6 (7.4) at day 10 (P = .81). Conclusions and relevance: The Infectious Diseases Society of America/American Thoracic Society recommendations for duration of antibiotic treatment based on clinical stability criteria can be safely implemented in hospitalized patients with CAP. Trial registration: clinicaltrialsregister.eu Identifier: 2011-001067-51.
Article
Full-text available
The recent widespread emergence of carbapenem resistance in Enterobacteriaceae is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the importance of this mobility in short-term evolution, such as within nosocomial outbreaks, is unknown. Using a combination of short- and long-read whole-genome sequencing of 281 blaKPC -positive Enterobacteriaceae isolates from a single hospital over 5 years, we demonstrate rapid dissemination of this carbapenem resistance gene to multiple species, strains, and plasmids. Mobility of blaKPC occurs at multiple nested genetic levels, with transmission of blaKPC strains between individuals, frequent transfer of blaKPC plasmids between strains/species, and frequent transposition of blaKPC transposon Tn4401 between plasmids. We also identify a common insertion site for Tn4401 within various Tn2-like elements, suggesting that homologous recombination between Tn2-like elements has enhanced the spread of Tn4401 between different plasmid vectors. Furthermore, while short-read sequencing has known limitations for plasmid assembly, various studies have attempted to overcome this by the use of reference-based methods. We also demonstrate that, as a consequence of the genetic mobility observed in this study, plasmid structures can be extremely dynamic, and therefore these reference-based methods, as well as traditional partial typing methods, can produce very misleading conclusions. Overall, our findings demonstrate that nonclonal resistance gene dissemination can be extremely rapid, presenting significant challenges for public health surveillance and achieving effective control of antibiotic resistance.
Article
Full-text available
Objectives: The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance. Methods: We searched four databases to July 2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes. Results: Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants [median 70% (IQR 50%-84%); n = 8 studies] had heard of antibiotic resistance, but most [median 88% (IQR 86%-89%); n = 2 studies] believed it referred to changes in the human body. Many believed excessive antibiotic use [median 70% (IQR 59%-77%); n = 11 studies] and not completing antibiotic courses [median 62% (IQR 47%-77%); n = 8 studies] caused resistance. Most participants nominated reducing antibiotic use [median 74% (IQR 72%-85%); n = 4 studies] and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians. Conclusions: The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.
Article
Full-text available
The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear. We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections. Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes. In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).
Article
Full-text available
The objective of this study was to establish how antibiotic prescribing policies at National Health Service (NHS) hospitals match the England Department of Health 'Start Smart-Then Focus' recommendations and relate to Clostridium difficile infection (CDI) rates. Antibiotic pharmacists were surveyed regarding recommendations for empirical treatment of common syndromes ('Start Smart') and antimicrobial prescription reviews ('Focus') at their hospital trusts. If no response was provided, policy data were sought from trust websites and the MicroGuide app (Horizon Strategic Partners, UK). Empirical treatment recommendations were categorized as broad spectrum (a β-lactam penicillin/β-lactamase inhibitor, cephalosporin, quinolone or carbapenem) or narrow spectrum. CDI rates were gathered from the national mandatory surveillance system. Data were obtained for 105/145 English acute hospital trusts (72%). β-Lactam/β-lactamase inhibitor combinations were recommended extensively. Only for severe community-acquired pneumonia and pyelonephritis were narrow-spectrum agents recommended first line at a substantial number of trusts [42/105 (40%) and 50/105 (48%), respectively]. Policies commonly recommended dual therapy with aminoglycosides and β-lactams for abdominal sepsis [40/93 trusts (43%)] and undifferentiated severe sepsis [54/94 trusts (57%)]. Most policies recommended treating for ≥7 days for most indications. Nearly all policies [100/105 trusts (95%)] recommended antimicrobial prescription reviews, but only 46/96 respondents (48%) reported monitoring compliance. Independent predictors of higher CDI rates were recommending a broad-spectrum regimen for community-acquired pneumonia (P = 0.06) and, counterintuitively, a recommended treatment duration of <48 h for nosocomial pneumonia (P = 0.01). Hospital antibiotic policies in the NHS 'Start Smart' by recommending broad-spectrum antibiotics for empirical therapy, but this may have the unintended potential to increase the use of broad-spectrum antibiotics and risk of CDI unless better mechanisms are in place to improve 'Focus'. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Article
In ad 321, Roman Emperor Constantine the Great codified that there would be 7 days in a week. Even in the modern era of evidence-based-medicine, this 1695-year-old decree remains a primary reference for duration of antibiotic therapy: it leads physicians to treat infections in intervals of 7 days. Thus, it is gratifying when clinical trials challenge the standard antibiotic duration of 7 to 14 days.