Duration of antibiotic therapy and resistance
Published in Health News and Evidence
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Practice points for prescribers | Practice points for pharmacists | Use of antibiotics in Australia and the emergence of resistance | Duration of antibiotic therapy | Assist patients to adhere to the intended duration of therapy | References
Continued overuse and misuse of antibiotics means that one day we risk losing the effect of these vital medicines. Good prescribing practices can minimise antibiotic resistance in the community. One way to stop its progress is to restrict the use of antibiotics and minimise the duration of therapy when possible. It is also essential that patients do not exceed the intended duration of treatment.
- Consider the nature and severity of the infection and the person’s immune status, and prescribe antibiotics when benefits are likely to be substantial.
- Refer to the antibiotic guidelines (Therapeutic Guidelines: Antibiotics, Australian Medicines Handbook) for the recommended duration of antibiotic therapy, or, where applicable, local evidence-based guidelines.
- When prescribing antibiotics, specify duration of treatment.
- Bear in mind that the shorter the duration of treatment, the lower the selection pressure for resistance is in the patient.
- Do not provide repeat prescriptions unless required (consider removing the default for repeat prescription in medical software).
- Consider including an expiry date on prescriptions to prevent them from being filled after anticipated resolution of infection.
- Advise patients to take the antibiotics as directed, even if this means there are antibiotics remaining.
- Evaluate the need to continue, revise or stop antibiotic treatment based on clinical response and available microbiological data.
- Reinforce directions for use.
- When there is concern that remaining antibiotics may be misused, consider dispensing the number of antibiotics required for the indicated duration of treatment, even if this means removing some tablets from a pack.
- Advise patients to dispose of unused antibiotics when the pack size is greater than needed for duration of therapy.
- Question people who return with a repeat prescription after a long period of time when it would be expected that the original infection would have resolved.
Antibiotics are one of the most commonly prescribed medicines in general practice.1 However, they are frequently overused and misused,2 which can cause harm to individuals and the community as a whole.
At the level of an individual, antibiotics can cause adverse events, they can be costly and recent use increases the likelihood of an individual carrying a resistant bacterial strain, which places them at risk if a subsequent infection is not treatable.3–6 There are also implications for those they come in contact with, as resistant bacteria can be transmitted to others.4
At a population level, widespread use promotes antibiotic resistance that can persist within communities.7,8 In the past 20 years the number of common pathogens resistant to antibiotics has significantly increased. For example, Streptococcus pneumoniae resistance to macrolide antibiotics has increased from 8.7% in 1994 to 20.4% in 2007, and this trend is continuing.9
Read more about antibiotic resistance in our NPS News publication Antibiotic resistance – a problem for everyone.
Following prescribing principles can minimise antibiotic resistance
Prescribers of antibiotics are in a prime position to address antibiotic resistance. One way to lower the rate of antibiotic-resistant bacteria in the population is to reduce the use of antibiotics in the community.
Preserve and prescribe antibiotics for clinical situations when they will be of substantial benefit to patients.10–12 For example, consider if antibiotics are appropriate for an acute respiratory tract infection or if self-management of symptoms is more appropriate. Read more about methods to encourage patient self-management of acute respiratory tract infection.
Select an appropriate narrow-spectrum, rather than broad-spectrum, antibiotic for the infection, based on antibiotic guidelines, and prescribe at the appropriate dose and for the appropriate duration.12 For example, consider if amoxycillin alone is appropriate rather than amoxycillin with clavulanic acid (Augmentin).
For other good prescribing practices, refer to the antimicrobial creed developed by the Australian Therapeutic Guidelines (Table 1).12
Table 1: The antimicrobial creed12
Optimal duration of antibiotic therapy
The duration of antibiotic therapy needs to be sufficient to control the bacterial infection and prevent relapse. When optimising therapy for an infection consider the person’s immune status, the infecting agent and the focus of infection.5
Refer to antibiotic guidelines for the recommended durations of antibiotic therapy, including Therapeutic Guidelines: Antibiotics,12 the Australian Medicines Handbook,13 or, where applicable, local evidence-based guidelines.
The optimal duration of antibiotic therapy for many infections is well defined, such as for UTIs and pneumonia.12 However, it may be surprising to learn there is a lack of randomised clinical trials to establish the course of therapy for many common infections.14 It is difficult to change prescribing practices to shorten antibiotic courses without strong evidence supporting the safety and efficacy.15
Longer exposure to antibiotics can contribute to resistance
Several trials have demonstrated that longer antibiotic therapy encourages the development or acquisition of antibiotic-resistant organisms.4,11,16 For example, in one study penicillin resistance risk increased by 4% for each day of beta-lactam antibiotic taken in the preceding 6 months.4 Another study demonstrated that a low daily dose and a long duration of treatment with oral beta-lactam correlated with penicillin-resistant pneumococcal carriage in children.16
Longer exposure also appears to have risks and harms for the patient, such as:
- increased risk of adverse effects from antibiotic therapy, such as diarrhoea, nausea and vomiting.13
- difficulties with adherence.5
- costly treatment for some antibiotics.
Stopping antibiotics before end of recommended treatment
Non-adherence with antibiotic therapy may be more common than most GPs realise. In patients given a prescription for respiratory symptoms, a recent study demonstrated that > 41% did not take them and only about 44% took the prescribed course.17
So, if a patient is feeling much better after taking a part of their prescribed course of antibiotics, is there harm is stopping the antibiotics early?
There does not appear to be strong evidence to support the notion that stopping antibiotics before the end of the recommended treatment contributes to increasing resistance.16,18 Therefore, in selected cases, it may be appropriate to stop antibiotic therapy early.
However, if a person takes an inadequate course of antibiotics, they may relapse and require further treatment.12 This increases the risk of developing resistance, as it would expose the person to antibiotics for longer.
Shorter courses of antibiotic therapy may be appropriate
For some infections, such as Staphylococcus aureus bacteraemia, enterococcal endocarditis or tuberculosis, clear evidence favours prolonged treatment to prevent relapse.5
However, it is advisable to keep duration of therapy as short as possible, unless otherwise indicated, as this may lower the selection pressure and help prevent resistance in the individual.12,19
Shorter course of antibiotic therapy have been very successful in treating some infections, such as a 3-day course for uncomplicated UTIs in women.12,15
In general it is thought that short duration of antibiotic therapy results in similar outcomes to those of longer courses.20–22 For example, cure without recurrence for uncomplicated cellulitis was shown to be the same for people treated for 5 or 10 days.22 Also, shorter courses of antibiotics are associated with similar or fewer complications than prolonged therapy.23
However, clinical studies of routine infectious illnesses are required to define the minimum safe courses and the optimal therapeutic regimens.15
Patients may be confused if they receive more antibiotics than they require or are given a repeat prescription unnecessarily. To reduce the misuse of antibiotics, ensure patients understand, and are supported in adhering to, the intended duration of therapy.
It may also be helpful to advise patients to:
- take only the number of antibiotics as directed, even if this means there are some antibiotics remaining
- dispose of any remaining antibiotics by returning them to a pharmacy
- not keep remaining antibiotics to use at a later date
- not give their antibiotics to another person to use
- avoid unnecessary repeat prescriptions.
- Britt H, Miller C, Charles J, et al. General practice activity in Australia 2011–12. Sydney: Bettering the Evaluation and Care of Health, 2012.
- Arason VA, Sigurdsson JA. The problems of antibiotic overuse. Scand J Prim Health Care 2010;28:65–6. [PubMed]
- Chung A, Perera R, Brueggemann AB, et al. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: prospective cohort study. BMJ 2007;335:429. [PubMed]
- Nasrin D, Collignon PJ, Roberts L, et al. Effect of beta lactam antibiotic use in children on pneumococcal resistance to penicillin: prospective cohort study. BMJ 2002;324:28–30. [PubMed]
- Paul J. What is the optimal duration of antibiotic therapy? BMJ 2006;332:1358. [PubMed]
- Costelloe C, Metcalfe C, Lovering A, et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010;340:c2096. [PubMed]
- Enne VI, Livermore DM, Stephens P, et al. Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction. Lancet 2001;357:1325–8. [PubMed]
- Sundqvist M, Geli P, Andersson DI, et al. Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use. J Antimicrob Chemother 2010;65:350–60. [PubMed]
- (AGAR) AGoAR. Streptococcus pneumoniae survey. 2007. http://www.agargroup.org/files/SPNE%2007%20report%20final.pdf (accessed 29 May 2013).
- Austin DJ, Kristinsson KG, Anderson RM. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci USA 1999;96:1152–6. [PubMed]
- Guillemot D, Varon E, Bernede C, et al. Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae. Clin Infect Dis 2005;41:930–8. [PubMed]
- Therapeutic Guidelines Limited. Antiobitics 2010. http://www.tg.org.au/index.php?sectionid=41 (accessed 28 May 2013).
- Australian Medicines Handbook. Chapter 5: Anti-infectives. 2013. http://amh.hcn.com.au/view.php?page=chapter5/index.html (accessed 28 May 2013).
Horsburgh CR, Shea KM, Phillips P, et al. Randomized clinical trials to identify optimal antibiotic treatment duration. Trials 2013;14:88. [PubMed]
- 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;46:491–6. [PubMed]
- Guillemot D, Carbon C, Balkau B, et al. Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998;279:365–70. [PubMed]
- Francis NA, Gillespie D, Nuttall J, et al. Antibiotics for acute cough: an international observational study of patient adherence in primary care. Br J Gen Pract 2012;62:e429–37. [PubMed]
- Pichicero M. Short courses of antibiotic in acute otitis media and sinusitis infections. J Int Med Res 2000;28 Suppl 1:25A–36A. [PubMed]
- Rubinstein E, Keynan Y. Short-course therapy for severe infections. Int J Antimicrob Agents 2013. [Epub ahead of print] [PubMed]
- Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003;290:2588–98. [PubMed]
- Schein M, Assalia A, Bachus H. Minimal antibiotic therapy after emergency abdominal surgery: a prospective study. Br J Surg 1994;81:989–91. [PubMed]
- Hepburn MJ, Dooley DP, Skidmore PJ, et al. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med 2004;164:1669–74. [PubMed]
- Hedrick TL, Evans HL, Smith RL, et al. Can we define the ideal duration of antibiotic therapy? Surg Infect (Larchmt) 2006;7:419–32. [PubMed]