The antibiotic course has had its day

BMJ 2017; 358 doi: (Published 26 July 2017) Cite this as: BMJ 2017;358:j3418

Re: The antibiotic course has had its day

In this “Analysis”, Llewelyn et al argue that clinicians put patients at unnecessary risk when prescribing standard duration of antibiotics, advising them to defect from international “complete the course” recommendations.1

I would, however, argue that these authors’ rational is based on vague assumptions and that robust evidence on the causality of the spread of antibacterial drug resistance in the community is needed before making such claim.

First, the authors state that antibiotic use replaces commensal flora of the gut or skin with “resistant species and strains ready to cause infection in the future” 1 However, their argument is based on a study that only observed selection of non-ESKAPE resistant bacteria such as coagulase-negative staphylococci and oral nongroupable streptococci.2 In addition, ESKAPE organisms including Pseudomonas spp or Staphylococcus aureus were not isolated, outright refuting the authors main claim.1

Second, although most antibiotics (85%) prescribed are issued in primary care, for many of these drugs (e.g. amoxicillin used for respiratory tract or ear infections) no safe narrow-spectrum alternatives exist.3 Also, drug resistance to broad-spectrum antibiotics (e.g. piperacillin/tazobactam or carbapenems) amongst ESKAPE organisms has largely emerged from over-prescribing in hospital settings rather than primary care where these drugs are not available.4

Third, the authors also ignore other important forms of selection pressure on bacteria such as farming and the food industry, easy over-the-counter access to antibiotics overseas, and patients borrowing drugs from friends or family for minor illnesses.

Fourth, the authors also claim that drug resistant bacteria are “transmitted between asymptomatic carriers rather than people with disease”. Again, the paper cited to back up their argument describes a within-hospital outbreak of carbapenem-resistant Enterobacter spp with little or no evidence for import from or spread to the local community.5 Therefore, claiming a simple link between fixed-course antibiotic regimens and the spread of drug resistance in the population, combined with advice that patients shorten the duration of their treatment, is speculative at its best and dangerous at its worst. Therefore, before making such a claim the authors should provide rigorous analysis of epidemiologic and phylogenetic data (as has been done for HIV, malaria, and TB) to back up their argument.6

As a primary care clinician, I would be very happy to prescribe shorter treatments if clear evidence for doing so was available from systematic reviews or randomised controlled trials. Until proven otherwise, however, I will not change my prescribing behaviour and continue to provide the “complete the course” standard of care to my patients for the sake of their safety and for medico-legal reasons.

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 [published Online First: 2017/07/28]
2. Cremieux AC, Muller-Serieys C, Panhard X, et al. Emergence of resistance in normal human aerobic commensal flora during telithromycin and amoxicillin-clavulanic acid treatments. Antimicrobial agents and chemotherapy 2003;47(6):2030-5. [published Online First: 2003/05/23]
3. Schneider-Lindner V, Quach C, Hanley JA, et al. Secular trends of antibacterial prescribing in UK paediatric primary care. The Journal of antimicrobial chemotherapy 2011;66(2):424-33. doi: 10.1093/jac/dkq452 [published Online First: 2010/12/22]
4. Lob SH, Hackel MA, Kazmierczak KM, et al. In Vitro Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program). Antimicrobial agents and chemotherapy 2017;61(6) doi: 10.1128/aac.02209-16 [published Online First: 2017/03/23]
5. Sheppard AE, Stoesser N, Wilson DJ, et al. Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene blaKPC. Antimicrobial agents and chemotherapy 2016;60(6):3767-78. doi: 10.1128/aac.00464-16 [published Online First: 2016/04/14]
6. Wilson BA, Garud NR, Feder AF, et al. The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens. Molecular ecology 2016;25(1):42-66. doi: 10.1111/mec.13474 [published Online First: 2015/11/19]

Competing interests: No competing interests

04 August 2017
Werner Leber
NIHR CLAHRC Clinical Lecturer in Primary Care
Centre for Primary Care and Public Health, Blizard Institute, Queen Mary University of London