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Unwanted consequences of suboptimal antimicrobial use, such as higher costs and resistance, have led institutions to set up programmes for optimising use. Here, strategies are discussed
PhD student/Ad Hoc Lecturer
School of Pharmacy
The Robert Gordon University
Antimicrobial resistance and the threat it brings have long been recognised. Inherent resistance existed even before antimicrobials were introduced into medicine; in 1940, Abraham and Chain recognised acquired antimicrobial resistance when,
during the development of penicillin, they isolated the enzyme (penicillinase) that destroys penicillin.
There is a complex relationship between antimicrobial use and the development of resistance. Most authorities believe this association is certain.[2,3] However, surprisingly, there is little evidence to support this, mainly due to many confounding variables that are hard to control for in trials.[3,4] Trials directly linking antibiotic use with resistance are now being undertaken.[5,6]
Resistance has economic and clinical consequences, with increased overall treatment costs due to prolonged illness and resistance to cheaper first-line antimicrobials making it necessary to use more costly drugs. Resistance has been compounded by factors in secondary care, including hospital overcrowding leading to cross-infection, immunosuppression (disease or therapeutic) and the use of more invasive techniques allowing easy bacterial entry into the patient’s body. This problem is becoming ever more urgent due to
the lack of development of antimicrobials with novel modes of action. As one author has put it: “Antibiotics should be thought of like oil: a non-renewable resource to be carefully husbanded. What we use now cannot be used some time in the future.”
Evidence for suboptimal antimicrobial use appears as far back as 1972, when a pioneering report indicated that 65% of antibiotics were prescribed inappropriately. US estimates suggest up to 55% of antibiotic prescriptions prescribed in ambulatory care for acute respiratory infections may have been needless.
The extensive and sometimes suboptimal use of antimicrobials, in both primary and secondary care, has prompted various organisations to develop initiatives to optimise antimicrobial use.[7,11-15] The fact that antimicrobials make up a substantial portion of hospital drug budgets also makes it essential to promote their optimal use. This review will provide an overview of some different strategies to implement antimicrobial stewardship programmes (other terms, often used
interchangeably, include “antibiotic policies”, “antibiotic management programmes” and “antibiotic control programmes”). These are generally classified in terms of the way in which they influence antimicrobial use. The programmes need to consider ways to ensure appropriate and cost-effective use of antimicrobials. Table 1 explains some key terms related to this topic.
Strategies to optimise antimicrobial use
Formulary limitation was one of the earliest systems implemented and is the most direct way to control which antimicrobials are on the formulary, minimising the pharmacological class of antimicrobials available and the number of agents from each pharmacological class.[17,18] The underlying rationale is that the fewer antimicrobials there are available to which organisms are exposed, the less likely it is for resistance to develop. However, evidence backing the long-term consequences of this is lacking. Besides, this does not avoid
overuse of existing broad-spectrum antimicrobials.[17,18]
Critics of such an approach favour an “open formulary”. This involves unrestricted use of any antimicrobial and will result in less selection pressure, so less resistance. [4,9] Formulary limitation may also lead to negative patient outcomes when the most suitable antimicrobial in a specific clinical scenario is not available. Methods for implementing formulary systems have included antimicrobial order forms, therapeutic interchange and
antimicrobial cycling programmes. Evidence of efficacity is limited in each case, especially the latter two. Antimicrobial order forms may offer a way to facilitate implementation of guidelines, so may be useful as part of a multifaceted programme aimed at optimising antimicrobial use. However, they are often implemented by the pharmacy department; this may cause antagonism between pharmacy and prescriber, particularly when the latter does not prescribe according to
guidance issued by the specific institution.
Some institutions incorporate automatic stop-orders as part of antimicrobial order forms, particularly when prescribing for surgical prophylaxis. However, particular caution must be exercised here to ensure there are no inadvertent lapses in a patient’s medication.
Formulary restriction works by limiting access to certain
antimicrobials. Various ways of restricting agents have been reported: monitoring use via the pharmacy and referring to the infectious diseases department when specific antimicrobials have been prescribed, or limiting specific antimicrobials to particular disease states or locations and requiring preapproval from or consultation by an infectious diseases physician. In
theory, restriction approaches may pose the same problems regarding resistance, since the restriction may well result in increased use of another antimicrobial within the same class.[4,19] Restriction may also delay patient access to the appropriate antimicrobial.
Clinical pathways include peer-reviewed guidelines published by national and international bodies, or guidelines specific to the institution that may take local resistance patterns into consideration. The overall aim is usually to produce an algorithm for management, so limiting the number of antimicrobials available for managing a specific condition. The major problem here is that the success of clinical pathways very
much depends on whether these are effectively implemented,
with passive education likely to be ineffective; there is also a need for frequent updating of guidelines.[16-19] Use of electronic prescribing aids, such as computer decision support, may be considered a way to implement clinical pathways. These may be particularly useful when linked to patient records such that patients’ individual characteristics are taken into consideration when choosing the more appropriate antimicrobials. However, setting up sophisticated systems
demands significant time and resources.
Streamlining (also known as review and feedback, or postprescribing evaluation) involves narrowing the spectrum of empirical therapy (or stopping antimicrobials if not required), which is usually broad, once microbiological results are available, usually some 48-72 hours after treatment initiation. Individuals screening the data (usually pharmacy personnel) then give feedback to the prescribers, making recommendations for any changes required to current therapy. Evidence suggests such an approach reduces costs and exposure to unnecessary antimicrobial treatment.[4,17] Selective reporting of sensitivities may also be incorporated, limiting the choice of antimicrobials made available.[4,9] The success of such a strategy requires prescribers to accept and make any changes recommended.
Intravenous-to-oral conversion is one of the most commonly documented adjustments. Patients admitted to hospital are often acutely unwell and need parenteral therapy at the start of treatment. Potential candidates for oral therapy (including patients who are haemodynamically stable, who have improved clinically over 48 hours or with functioning gastrointestinal tracts) are evaluated, usually by a pharmacist, and recommendations made to the prescriber to switch to oral
treatment.[4,17] Antimicrobials with good oral bioavailability
are especially suitable for such programmes. This approach may cut hospital stay, costs and complications related to intravenous access, including phlebitis and catheter-related infections, but no improvements in clinical outcomes have been reported.
Prescriber education aims at informing clinicians about and attempting to influence adherence to guidelines regarded by an institution as a desirable standard. Programmes reported include mailing educational material, one-to-one prescribing education and peer review of prescribing habits with feedback, and have often involved pharmacists.[4,16] Yet there is little consensus as to which would be optimal – whether one should take a one-to-one or less personalised approach. Such approaches form part of most stewardship programmes, but their effectiveness will rely on prescriber uptake and willingness and motivation to sustain any changes in behaviour. Probably, education will only be effective in changing prescribing practices
if passive input is followed by more active measures, such as prospective audit and intervention.
Lack of evidence, particularly around patient outcomes, makes it impossible to decide conclusively whether any particular approach is superior to any other. However, it is clear that the approaches used need to be tailored to the institution in which they will be implemented and to take into consideration factors such as hospital size, special patient populations, local resistance patterns, financial resources and constraints, and internal politics. The aim of implementing the programme should
also be clearly defined – the approach would differ if one wanted to control an outbreak of a resistant organism compared with producing a sustained reduction in resistance. Often, more than one approach may be needed. Programmes involving a multidisciplinary team seem to be the way forward when attempting to implement strategies aimed at optimising antimicrobial use in secondary care.[11,16,17,19,22-24] These involve a core group comprising an infectious diseases physician
and a clinical pharmacist trained in infectious diseases, backed by infection control and microbiology departments and the hospital administration.
1. Abraham EP, Chain E. An enzyme from bacteria able to
destroy penicillin. Rev Infect Dis 1988;10:677-8.
2. Livermore DM. Minimising antibiotic resistance. Lancet Infect Dis 2005;5:450-9.
3. Gould IM. A review of the role of antibiotic policies in the control of antibiotic resistance. J Antimicrob Chemother 1999;43:459-65.
4. Bearden DT, Allen GP. Impact of antimicrobial control
programs on patient outcomes. Dis Manage Health Outcomes 2003;11:723-36.
5. Chung A, et al. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care. Br Med J 2007;335:429-31.
6. Malhatra-Kumar S, et al. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers. Lancet 2007;369:482-90.
7. World Health Organization. WHO global strategy for
containment of antimicrobial resistance. Geneva: WHO; 2001.
8. Del Mar C. Prescribing antibiotics in primary care. Br Med J 2007;335:407-8.
9. Klem C, Dasta JF. Efforts of pharmacy to reduce antibiotic resistance. New Horiz 1996;4:377-84.
10. Gonzales R, et al. Excessive antibiotic use for acute
respiratory infections in the United States. Clin Infect Dis
11. EU. The microbial threat. Copenhagen: Danish Ministry of Health/Ministry of Food, Agriculture and Fisheries; 1998.
12. UK Parliament. Resistance to antibiotics and other
antimicrobial agents. London: HMSO; 1998.
13. UK Department of Health. UK antimicrobial resistance strategy and action plan. London: DH; 2000.
14. Scottish Executive. Antimicrobial resistance strategy and Scottish action plan. Edinburgh: Scottish Executive; 2002.
15. Scottish Medicines Consortium/Healthcare Associated Infection Taskforce. Antimicrobial prescribing policy and practice in Scotland. Edinburgh: Scottish Executive; 2005.
16. MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev 2005;18:638-56.
17. Paskovaty A, et al. A multidisciplinary approach to
antimicrobial stewardship. Int J Antimicrob Agents 2005;25:1-10.
18. Fishman N. Antimicrobial stewardship. Am J Infect Control 2006;34:S55-S63.
19. Dellit TH, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159-77.
20. Duncan RA. Controlling use of antimicrobial agents. Infect Control Hosp Epidemiol 1997;18:260-6.
21. Paterson DL. The role of antimicrobial management
programs in optimizing antibiotic prescribing within hospitals. Clin Infect Dis 2006;42:S90-5.
22. Knox K, et al. Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist. J Hosp Infect 2003;53:85-90.
23. Struelens MJ. Multidisciplinary antimicrobial management teams. Curr Opin Infect Dis 2003;16:305-7.
24. Owens RC, et al. Antimicrobial stewardship programs as a means to optimize antimicrobial use. Pharmacotherapy 2004;24:896-908.
25. World Health Organization. Prevention of hospital-acquired infections. Valletta: WHO; 2002.
26. Ramirez JA. Switch therapy with beta lactam/beta lactamase inhibitors in patients with community-acquired
pneumonia. Ann Pharmacother 1998;32:S22-6.