Antimicrobial stewardship: Short-course antibiotic therapy

CCDR

Volume 48-11/12, November/December 2022: Antimicrobial Use and Stewardship

Editorial

Short-course antibiotic therapy: The next frontier in antimicrobial stewardship

Donald Sheppard1,2,3,4

Affiliations

1 Antimicrobial Resistance Task Force, Public Health Agency of Canada, Ottawa, ON

2 Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, QC

3 Infectious Disease and Immunity in Global Health, Research Institute of McGill University Health Center, Montréal, QC

4 McGill Interdisciplinary Initiative in Infection and Immunity, Montréal, QC

Correspondence

donald.sheppard@phac-aspc.gc.ca

Suggested citation

Sheppard DC. Short-course antibiotic therapy: The next frontier in antimicrobial stewardship. Can Commun Dis Rep 2022;48(11/12):496–501. https://doi.org/10.14745/ccdr.v48i1112a01

Keywords: antibiotic therapy, duration, antimicrobial, stewardship, short-course antibiotherapy, antimicrobial resistance

Abstract

Ensuring appropriate use of antibiotics is critical to preserving their effectiveness through limiting the development and spread of antimicrobial resistance. Evidence is accumulating that shorter courses of antibiotics are as effective as traditional longer regimens for many common infections and can reduce the risk of adverse events. Despite the availability of evidence and guidelines supporting short-course antibiotic therapy for these conditions, prolonged use of antibiotics remains common. This article will review the origins and evolution of our approach regarding antimicrobial prescription duration, the evidence for the use of short-course therapy for selected infections, barriers to the uptake of this practice and potential approaches that can be taken to reduce inappropriately long antibiotic use.

Introduction

Antibiotics have transformed modern medicine, but their continued viability is threatened by rising rates of antimicrobial resistance (AMR). Limiting inappropriate use of antibiotics is an important approach to reducing the antibiotic pressure that can accelerate the evolution and spread of AMR. Evidence is emerging that for many common infections, short-course antibiotic therapy (1–7 days) can be equally as effective as traditional, longer courses of treatment Footnote 1 Footnote 2. Expanded use of short-course antibiotic therapy has the potential to reduce healthcare costs, reduce risks of adverse drug events and help curb AMR. This editorial will review the history of the development of antibiotic treatment duration, highlight key evidence for appropriate reductions in antibiotic therapy duration, and outline future directions in antimicrobial stewardship and knowledge generation that could support the reduction of unnecessary prolonged antibiotic therapy.

Origins of the current approach to antibiotic therapy duration

The modern antibiotic era began with the introduction of penicillin in 1940, and with it, the dilemma of determining the appropriate duration of therapy for infectious diseases. Albert Alexander, a British constable, was the first human to receive penicillin therapy for extensive streptococcal and staphylococcal facial abscesses following an injury sustained in a bombing raid Footnote 3. Constable Alexander received five days of penicillin therapy with an excellent short-term response; however, despite attempt to re-purify penicillin from his urine, the supply of purified penicillin was exhausted and therapy was discontinued as a result. Sadly, within several weeks, his infection returned and he eventually succumbed to his disease. While this first use of penicillin demonstrated the power of antibiotics to treat bacterial infections, it also presaged the current challenge of determining antibiotic therapy duration, highlighting both the question of "how much is enough", and the legitimate fear that inadequate therapy may result in relapse or poorer outcomes.

Despite this somewhat disheartening first experience with short-course antibiotic therapy, early prescribers of penicillin reported that 1.5–4 days of treatment was sufficient to cure the majority of patients with diseases like pneumococcal pneumonia Footnote 1. Indeed, one of the earliest trials of penicillin therapy for pneumococcal pneumonia demonstrated that when therapy was discontinued 2–3 days after clinical improvement and resolution of fever, only 3 of 54 patients relapsed after initial therapy Footnote 4. One of these cases occurred in a patient receiving only 24 hours of therapy, and in the other two cases the strain at relapse was found to be a different serotype than the original infecting isolate, suggesting a reinfection rather than a relapse Footnote 4. Collectively these observations suggest that longer courses of 1–2 weeks of penicillin for pneumonia are unnecessary for the majority of patients.

Many factors have likely influenced the shift from this original approach of using antibiotics for short courses, tailored to patient responses, to the modern, longer, 1–2 weeks fixed duration of therapy Footnote 1. The rise in outpatient care and the shift away from intensive patient follow-up makes daily assessment of response to therapy less practical and favours the use of fixed duration prescriptions. Experience with infections that require longer term antibiotic therapy like tuberculosis and endocarditis may have influenced attitudes towards the duration of therapy required for all infectious diseases. Public perceptions of risk and the current medico-legal climate have also combined to create a culture of caution in modern medicine. As antibiotics are largely well tolerated and safe, there is always the temptation to extend prescription duration to reduce perceived risks of relapse. Finally, and perhaps most importantly, a perceived lack of rigorous evidence supporting shorter course antibiotic therapy limits prescriber confidence in breaking with traditional longer, fixed duration therapies Footnote 5.

The case for shortening antimicrobial duration of therapy in selected infections

Although antibiotics are commonly viewed as "safe" medications, the potential advantages of prolonging antibiotic therapy duration must be weighed against the costs and potential for harm. From an economic perspective, it has been estimated that the cost of antimicrobial prescribing in Canada exceeds $750 million per year Footnote 6. It is evident that reducing the duration of antibiotic therapy has significant potential to reduce these costs. Prolonged antibiotic therapy can also increase the chance of medication for adverse events or drug-drug interactions and has been linked to increased risk of Clostridioides difficile infection Footnote 7. One study reported that in patients with pneumonia receiving continued antibiotic therapy after discharge, each excess day of treatment was associated with a 5% increase in the odds of self-reported antibiotic-associated adverse events Footnote 8. Beyond these direct costs and risks, longer courses of antibiotic therapy have been linked to an increased burden of resistance Footnote 9. In a study of antibiotic therapy for ventilator-associated pneumonia, recurrent infections with multidrug-resistant organisms were more commonly observed in patients receiving antibiotic prescriptions of 18 days as compared with those receiving only eight days Footnote 10. These data may suggest a need to revisit the broad use of public health messaging that encourages patients to complete their course of antibiotic therapy even after they feel better. For many conditions, this practice may be unnecessary and actually favour the emergence of resistance Footnote 1.

Clinical trials comparing short- and long-course therapy are accumulating, and a common theme is emerging supporting equivalent or better outcomes with short-course therapy. Multiple trials have demonstrated that short-course therapy (1–3 days) is highly effective for the treatment of uncomplicated urinary tract infection Footnote 11 Footnote 12, and that pyelonephritis and urosepsis in adults can be treated with seven days of an appropriate agent Footnote 13 Footnote 14 Footnote 15. Similarly, studies in both community and hospital-acquired pneumonia comparing the efficacy of short-course (5–7 days) therapy have found equivalent efficacy, and reduced rates of adverse events when compared with longer courses of treatment Footnote 8 Footnote 16 Footnote 17. The efficacy of short-course therapy extends to severe infections as well. Three randomized controlled clinical trials have demonstrated the safety and efficacy of seven days of antibiotic therapy for bacteremia with gram-negative bacilli Footnote 18 Footnote 19 Footnote 20 Footnote 21. A single large study has even challenged the dogma that antibiotic therapy for the treatment of febrile neutropenia must be continued until neutrophil recovery Footnote 22. This trial reported that antibiotic therapy for febrile neutropenia could be safely discontinued in patients with resolution of fever and clinical recovery, irrespective of their neutrophil counts Footnote 22. In recognition of the mounting evidence for short-course therapy, the Association of Medical Microbiology and Infection Disease Canada has recently published a practice point summary of duration of antibiotic therapy for common infections highlighting recent evidence for reduced duration of antibiotic treatment in select infectious diseases syndromes Footnote 23.

While the majority of trials on the duration of antibiotic therapy have supported the use of short-course therapy, there are some notable exceptions. A single trial reported that a six-week course of antibiotic therapy had inferior outcomes than a 12 weeks for prosthetic joint infection Footnote 24, although a second trial found that eight weeks was equally effective as longer course therapy for early prosthetic joint infection Footnote 25. Several meta-analyses of treatment trials of streptococcal pharyngitis found that bacterial eradication rates were higher with 10-day courses of penicillin; these differences were less marked with non-penicillin antibiotic treatments Footnote 26 Footnote 27 Footnote 28. Finally, although trials of treatment for otitis media in children found that 5–7 days of antibiotic therapy was effective Footnote 29, a single trial in children under the age of two years reported that five days of therapy was less effective than 10 days Footnote 30. A detailed list of these and other studies of antibiotic treatment duration has been curated by Dr. Brad Spellberg, University of Southern California.

Awareness of evidence in support of short-course antibiotic therapy: a knowledge mobilization opportunity

Despite the availability of new recommendations and position pieces from professional associations, adherence to best practices in reducing inappropriately long antibiotic prescriptions remains suboptimal. International studies have reported high levels of unnecessarily prolonged antibiotic therapy in both primary care and hospital settings. A review of primary care data in England from 2013 to 2015 recorded an estimated 1.3 million days of excess antibiotic prescriptions Footnote 31. Similarly, a study of pneumonia treatment in the United States revealed that as many as two out of three patients received excess antibiotic therapy Footnote 8. Canadian data on the appropriateness of the duration of antibiotic prescriptions are relatively sparse. A recent report on a stewardship intervention in primary care reported that 29.3% of prescriptions for community-acquired infections were inappropriately long (defined as more than seven days) Footnote 32. This report likely underestimates the degree of inappropriately prolonged prescription as it included cystitis, for which three days of antibiotic therapy is the standard of care. Similar findings have been reported in long-term care centres; a province-wide review of antimicrobial use in long-term care found that 44.9% of prescriptions exceeded seven days' duration Footnote 33. A limited number of studies have also identified high levels of prolonged antibiotic therapy in the Canadian hospital setting. An early study of treatment for hospital-acquired pneumonia found that only 30% of patients were treated with an appropriate duration of antibiotics Footnote 34. A second retrospective survey of the treatment of ventilator-associated pneumonia in a large Canadian urban health region found that more than 50% of patients received inappropriately prolonged antibiotic therapy Footnote 35. Collectively, these data suggest there is significant room for improvement in ensuring appropriate duration of antibiotic therapy in both the Canadian community and hospital sectors.

Behavioural science studies are beginning to shed light on the drivers underlying the continued use of prolonged antibiotic treatments by prescribers. International trials have suggested that prescriber preference and habit, rather than patient characteristics are the primary determinant of duration of antibiotic prescription trials Footnote 36, an observation that was replicated in the Canadian long-term care setting Footnote 33. Building on these findings, a recent behaviour change analysis in Canadian long-term care institutions highlighted a number of barriers to improving uptake of short-term antibiotic therapy, including a perceived lack of evidence, the often incorrect belief that short-course therapy could increase rates of antimicrobial resistance, as well as the previously documented strong effects of prior habits and belief in guiding prescription behaviours Footnote 5.

There are multiple approaches that could be taken to improve the uptake of short-course antibiotics in Canada. Increasing the awareness of new guidelines for short-course antibiotic therapies should be a goal of stewardship programs and targeted awareness campaigns and should be incorporated into professional education and maintenance of competence. There is evidence that these types of stewardship interventions can improve appropriate antibiotic prescription duration. Use of a multifaceted program of clinician education, clinical decision aids, patient information and audit and feedback in the Canadian outpatient setting resulted in significantly lower rates of inappropriately long-prescription duration as compared with clinics that did not receive the intervention Footnote 32. In parallel, the inclusion of measures of appropriateness of the duration of antibiotic use in antimicrobial use surveillance and epidemiologic studies will be critical in identifying populations and settings where prolonged antibiotic use is high, as well as monitoring the effectiveness of interventions and awareness campaigns designed to reduce this overuse. Traditionally, most surveillance programs and epidemiologic studies of antimicrobial use have focused on quantitative measures of total antibiotic use and quality measures that are driven by matching diagnoses to prescriptions, but often do not capture the duration of therapy by indication. Looking forward, although evidence is slowly emerging that the mantra of "short is better" is often correct, it is by no means a universal truth. Further studies are required to validate some of the seminal studies referenced here, and to explore the appropriate duration of therapy for other infectious diseases where prolonged antibiotic therapy has been linked to the emergence of resistance, such as sternal surgical infections following cardiac surgery Footnote 37. As evidence emerges, it may be possible to develop a better scientific framework to guide our understanding of what factors determine the need for prolonged antibiotic therapy to allow better identification of clinical predictors that can guide prescription duration in specific patient populations. Finally, expanding behavioural science research to better understand the barriers and enablers to implementing short-course antibiotic therapy has the potential to guide the development of novel approaches to improve rates of appropriate antibiotic therapy duration. The potential of behavioural science to guide effective stewardship initiatives has been clearly demonstrated in the United Kingdom at the national scale. In 2014, social norm feedback was provided to high prescribers of antibiotics in the form of a letter from England's Chief Medical Officer, accompanied by a leaflet on appropriate antibiotic use Footnote 38. This single intervention resulted in a sustained 3.3% reduction in antibiotic prescriptions, approaching the level of the five-year United Kingdom target of a 4% reduction of antibiotic use in primary care Footnote 38.

Conclusion

Ensuring antibiotics are used for an appropriate duration has the potential to reduce cost, improve patient outcomes and reduce antimicrobial resistance. There are multiple opportunities to advance the use of short-course therapy in clinical infectious diseases in Canada, including 1) improving awareness and education of existing duration of therapy guidelines, 2) implementing effective surveillance for appropriateness of antimicrobial prescription duration and 3) conducting studies to identify both the optimal length of therapy across a wide range of infectious diseases syndromes and the behavioural factors underlying prescriber practises in order to guide interventions aimed at reducing inappropriately long antibiotic prescriptions.

Author's statement

DCS conceived and wrote the manuscript.

Competing interests

The author reports no competing interests.

Acknowledgements

The author would like to thank J Dënis for helpful comments.

Funding

No funding support was received for this editorial.

References

Footnote 1

Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis 2008;46(4):491–6. https://doi.org/10.1086/526535

Return to footnote 1 referrer

Footnote 2

Wald-Dickler N, Spellberg B. Short-course Antibiotic Therapy-Replacing Constantine Units With "Shorter Is Better". Clin Infect Dis 2019;69(9):1476–9. https://doi.org/10.1093/cid/ciy1134

Return to footnote 2 referrer

Footnote 3

Barrett M. Uncovering the truth behind the first man treated with the world's first antibiotic. The News Minute. May 30, 2018. https://www.thenewsminute.com/article/uncovering-truth-behind-first-man-treated-penicillin-world-s-first-antibiotic-82175

Return to footnote 3 referrer

Footnote 4

Meads M, Harris HW, Finland M, Wilcox C. Treatment of pneumococcal pneumonia with penicillin. N Engl J Med 1945;232:747–55. https://doi.org/10.1056/NEJM194506282322601

Return to footnote 4 referrer

Footnote 5

Langford BJ, Quirk J, Carey S, Daneman N, Garber GE. Influencing duration of antibiotic therapy: A behavior change analysis in long-term care. Am J Infect Control 2019;47(12):1409–14. https://doi.org/10.1016/j.ajic.2019.05.020

Return to footnote 5 referrer

Footnote 6

Public Health Agency of Canada. Canadian Antimicrobial Resistance Surveillance System Report, 2021. Ottawa, ON: PHAC; (modified 2022-04-25). https://www.canada.ca/en/public-health/services/publications/drugs-health-products/canadian-antimicrobial-resistance-surveillance-system-report-2021.html

Return to footnote 6 referrer

Footnote 7

Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011;53(1):42–8. https://doi.org/10.1093/cid/cir301

Return to footnote 7 referrer

Footnote 8

Vaughn VM, Flanders SA, Snyder A, Conlon A, Rogers MA, Malani AN, McLaughlin E, Bloemers S, Srinivasan A, Nagel J, Kaatz S, Osterholzer D, Thyagarajan R, Hsaiky L, Chopra V, Gandhi TN. Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study. Ann Intern Med 2019;171(3):153–63. https://doi.org/10.7326/M18-3640

Return to footnote 8 referrer

Footnote 9

Gjini E, Paupério FF, Ganusov VV. Treatment timing shifts the benefits of short and long antibiotic treatment over infection. Evol Med Public Health 2020;2020(1):249–63. https://doi.org/10.1093/emph/eoaa033

Return to footnote 9 referrer

Footnote 10

Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003;290(19):2588–98. https://doi.org/10.1001/jama.290.19.2588

Return to footnote 10 referrer

Footnote 11

Lutters M, Vogt-Ferrier NB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008;2008(3):CD001535. https://doi.org/10.1002/14651858.CD001535.pub2

Return to footnote 11 referrer

Footnote 12

Milo G, Katchman EA, Paul M, Christiaens T, Baerheim A, Leibovici L. Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2005;(2):CD004682. https://doi.org/10.1002/14651858.CD004682.pub2

Return to footnote 12 referrer

Footnote 13

Havey TC, Fowler RA, Daneman N. Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis. Crit Care 2011;15(6):R267. https://doi.org/10.1186/cc10545

Return to footnote 13 referrer

Footnote 14

Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE; 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(5):e103–20. https://doi.org/10.1093/cid/ciq257

Return to footnote 14 referrer

Footnote 15

Eliakim-Raz N, Yahav D, Paul M, Leibovici L. Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection-- 7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2013;68(10):2183–91. https://doi.org/10.1093/jac/dkt177

Return to footnote 15 referrer

Footnote 16

Tansarli GS, Mylonakis E. Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother 2018;62(9):e00635-18. https://doi.org/10.1128/AAC.00635-18

Return to footnote 16 referrer

Footnote 17

Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev 2015;2015(8):CD007577. https://doi.org/10.1002/14651858.CD007577.pub3

Return to footnote 17 referrer

Footnote 18

Molina J, Montero-Mateos E, Praena-Segovia J, León-Jiménez E, Natera C, López-Cortés LE, Valiente L, Rosso-Fernández CM, Herrero M, Aller-García AI, Cano Á, Gutiérrez-Gutiérrez B, Márquez-Gómez I, Álvarez-Marín R, Infante C, Roca C, Valiente-Méndez A, Pachón J, Reguera JM, Corzo-Delgado JE, Torre-Cisneros J, Rodríguez-Baño J, Cisneros JM; SHORTEN trial team. Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial. Clin Microbiol Infect 2022;28(4):550–7. https://doi.org/10.1016/j.cmi.2021.09.001

Return to footnote 18 referrer

Footnote 19

von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, Gayet-Ageron A, Huttner B, Kohler P, Lemmenmeier E, McCallin S, Rossel A, Harbarth S, Kaiser L, Bochud PY, Huttner A. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA 2020;323(21):2160–9. https://doi.org/10.1001/jama.2020.6348

Return to footnote 19 referrer

Footnote 20

Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis 2019;69(7):1091–8. https://doi.org/10.1093/cid/ciy1054

Return to footnote 20 referrer

Footnote 21

Tansarli GS, Andreatos N, Pliakos EE, Mylonakis E. A Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to Enterobacteriaceae. Antimicrob Agents Chemother 2019;63(5):e02495-18. https://doi.org/10.1128/AAC.02495-18

Return to footnote 21 referrer

Footnote 22

Aguilar-Guisado M, Espigado I, Martín-Peña A, Gudiol C, Royo-Cebrecos C, Falantes J, Vázquez-López L, Montero MI, Rosso-Fernández C, de la Luz Martino M, Parody R, González-Campos J, Garzón-López S, Calderón-Cabrera C, Barba P, Rodríguez N, Rovira M, Montero-Mateos E, Carratalá J, Pérez-Simón JA, Cisneros JM. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol 2017;4(12):e573–83. https://doi.org/10.1016/S2352-3026(17)30211-9

Return to footnote 22 referrer

Footnote 23

Grant J, Le Saux N. Duration of antibiotic therapy for common infections. JAMMI 2021;6(3):181–97. https://doi.org/10.3138/jammi-2021-04-29

Return to footnote 23 referrer

Footnote 24

Bernard L, Arvieux C, Brunschweiler B, Touchais S, Ansart S, Bru JP, Oziol E, Boeri C, Gras G, Druon J, Rosset P, Senneville E, Bentayeb H, Bouhour D, Le Moal G, Michon J, Aumaître H, Forestier E, Laffosse JM, Begué T, Chirouze C, Dauchy FA, Devaud E, Martha B, Burgot D, Boutoille D, Stindel E, Dinh A, Bemer P, Giraudeau B, Issartel B, Caille A. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. N Engl J Med 2021;384(21):1991–2001. https://doi.org/10.1056/NEJMoa2020198

Return to footnote 24 referrer

Footnote 25

Lora-Tamayo J, Euba G, Cobo J, Horcajada JP, Soriano A, Sandoval E, Pigrau C, Benito N, Falgueras L, Palomino J, Del Toro MD, Jover-Sáenz A, Iribarren JA, Sánchez-Somolinos M, Ramos A, Fernández-Sampedro M, Riera M, Baraia-Etxaburu JM, Ariza J; Prosthetic Joint Infection Group of the Spanish Network for Research in Infectious Diseases—REIPI. Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial. Int J Antimicrob Agents 2016;48(3):310–6. https://doi.org/10.1016/j.ijantimicag.2016.05.021

Return to footnote 25 referrer

Footnote 26

Altamimi S, Khalil A, Khalaiwi KA, Milner R, Pusic MV, Al Othman MA. Short versus standard duration antibiotic therapy for acute streptococcal pharyngitis in children. Cochrane Database Syst Rev 2009(1):CD004872. https://doi.org/10.1002/14651858.CD004872.pub2

Return to footnote 26 referrer

Footnote 27

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;2012(8):CD004872. https://doi.org/10.1002/14651858.CD004872.pub3

Return to footnote 27 referrer

Footnote 28

Holm AE, Llor C, Bjerrum L, Cordoba G. Short- vs. Long-Course Antibiotic Treatment for Acute Streptococcal Pharyngitis: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Antibiotics (Basel) 2020;9(11):733. https://doi.org/10.3390/antibiotics9110733

Return to footnote 28 referrer

Footnote 29

Kozyrskyj A, Klassen TP, Moffatt M, Harvey K. Short-course antibiotics for acute otitis media. Cochrane Database Syst Rev 2010;2010(9):CD001095. https://doi.org/10.1002/14651858.CD001095.pub2

Return to footnote 29 referrer

Footnote 30

Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, Martin JM, Kurs-Lasky M, Copelli SJ, Colborn DK, Block SL, Labella JJ, Lynch TG, Cohen NL, Haralam M, Pope MA, Nagg JP, Green MD, Shaikh N. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. N Engl J Med 2016;375(25):2446–56. https://doi.org/10.1056/NEJMoa1606043

Return to footnote 30 referrer

Footnote 31

Pouwels KB, Hopkins S, Llewelyn MJ, Walker AS, McNulty CA, Robotham JV. Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines. BMJ 2019;364:l440. https://doi.org/10.1136/bmj.l440

Return to footnote 31 referrer

Footnote 32

McIsaac W, Kukan S, Huszti E, Szadkowski L, O'Neill B, Virani S, Ivers N, Lall R, Toor N, Shah M, Alvi R, Bhatt A, Nakamachi Y, Morris AM. A pragmatic randomized trial of a primary care antimicrobial stewardship intervention in Ontario, Canada. BMC Fam Pract 2021;22(1):185. https://doi.org/10.1186/s12875-021-01536-3

Return to footnote 32 referrer

Footnote 33

Daneman N, Gruneir A, Bronskill SE, Newman A, Fischer HD, Rochon PA, Anderson GM, Bell CM. Prolonged antibiotic treatment in long-term care: role of the prescriber. JAMA Intern Med 2013;173(8):673–82. https://doi.org/10.1001/jamainternmed.2013.3029

Return to footnote 33 referrer

Footnote 34

Do J, Walker SA, Walker SE, Cornish W, Simor AE. Audit of antibiotic duration of therapy, appropriateness and outcome in patients with nosocomial pneumonia following the removal of an automatic stop-date policy. Eur J Clin Microbiol Infect Dis 2012;31(8):1819–31. https://doi.org/10.1007/s10096-011-1507-4

Return to footnote 34 referrer

Footnote 35

Chin T, Kushner B, Dersch-Mills D, Zuege DJ. Antibiotic Utilization Patterns in Patients with Ventilator-Associated Pneumonia: A Canadian Context. Can J Infect Dis Med Microbiol 2016;2016:3702625. https://doi.org/10.1155/2016/3702625

Return to footnote 35 referrer

Footnote 36

De Sutter AI, De Meyere MJ, De Maeseneer JM, Peersman WP. Antibiotic prescribing in acute infections of the nose or sinuses: a matter of personal habit? Fam Pract 2001;18(2):209–13. https://doi.org/10.1093/fampra/18.2.209

Return to footnote 36 referrer

Footnote 37

Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997;40(1):135–6. https://doi.org/10.1093/jac/40.1.135

Return to footnote 37 referrer

Footnote 38

Hallsworth M, Chadborn T, Sallis A, Sanders M, Berry D, Greaves F, Clements L, Davies SC. Provision of social norm feedback to high prescribers of antibiotics in general practice: a pragmatic national randomised controlled trial. Lancet 2016 Apr;387(10029):1743–52. https://doi.org/10.1016/S0140-6736(16)00215-4

Return to footnote 38 referrer

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