BSc PhD MPSNI MCPP CertMgt(OU) MIHMCertHealth
Director of Pharmacy
United Hospitals Trust
In 1998 the House of Lords Select Committee on Science and Technology reported that resistance to antibiotics and other anti-infective agents was a major threat to public health.(1) The need for action to improve prevention and control of infection, prescribing habits and surveillance was highlighted. Further, the UK government accepted the recommendations of the Standing Medical Advisory Committee (SMAC) in its document, The Path of Least Resistance.(2)
In June 2001, the European Commission proposed a Community strategy against antimicrobial resistance, which the Council of the EU accepted in November 2001 as a recommendation for Member States on the prudent use of antimicrobial agents in human medicine.(3) The key recommendations are listed in Table 1. Strategy documents have also been published in member countries.(4,5)
The use of antibiotics both inside and outside the hospital setting are important factors in the development of resistance, although many antibiotics are used solely, or primarily, in hospital. Dosages are often higher, creating a strong selective pressure for resistance in the hospital setting, especially in areas such as intensive care. Between 25 and 50% of hospitalised patients will receive antibiotics, and they constitute in the order of 20% of the total hospital drug spend.(6) In the UK this equates to a spend of £300m (e. 474.9) per annum.(7) Parenteral antibiotics are more expensive than the oral equivalents, and therefore the use of this formulation should be minimised; however, the National Audit Commission found wide variations in the ratio of parenteral to oral usage throughout the UK, ranging from 80:20 to 55:45.(7)
The rate of development of resistance to antibiotics appears to have accelerated in recent years.(8) An important contribution to increasing resistance is the extensive use of antibiotics, which also leads to increased costs and prolonged hospitalisation, for example with respect to the advent of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).(9,10) This substantial antibiotic use has also led to a marked increase in the number of Clostridium difficile infections,(11) placing a further financial burden on health services, the main factor being prolonged length of stay.(12,13)
It is imperative that antibiotic utilisation is optimised to prevent the further development of multidrug resistant bacteria that ultimately will not be treatable.
Strategies to improve antimicrobial prescribing in the hospital
There is no single remedy; rather a coordinated multidisciplinary approach is necessary, involving clinicians, consultant microbiologists and hospital pharmacists. It is this team approach that will enable the implementation of policies that will lead to improved prescribing.
A number of guidelines have been published with the aims of both optimising antimicrobial use and minimising resistance development.(14,15) The prime elements of antibiotic policies are presented in Table 2.
In terms of the success or otherwise of policies, research has shown that prescribers will adhere better to policies that have a substantive educational, rather than purely a restrictive, approach.(16)
Antibiotic formulary restrictions are among the most popular mechanisms for controlling antibiotic expenditure and inappropriate utilisation. A policy of not stocking nonformulary items in the pharmacy can also be effective. A requirement for written justification on automatic stock orders is a useful inclusion in a policy.(17) A further method of controlling antibiotic use is the division of antibiotics into three distinct groups:(18) freely available; based on microbiological report; or on consultant authorisation, or indeed a fourth category – consultant microbiologist authorisation only.
Prescriber education and feedback are vital for optimising antimicrobial use. Many studies have shown that doctors often prescribe antibiotics unnecessarily and inappropriately. (19) The Working Party of the British Society for Antimicrobial Chemotherapy highlighted the major factors that appear to influence physicians in the use of antibiotics.(14)
Medical staff should be provided with regular feedback reports on patterns of usage of antimicrobial agents, trends in sensitivity patterns and resistance to specific antibiotics. This system will be effective in directing the prescriber to the acceptable drug for the condition.(20,21)
Effectiveness of strategies
It has been shown that guidelines/protocols developed locally are more likely to be successful than regional or national policies, due to the sense of ownership.(22) In the treatment of respiratory tract infection, for example, it was demonstrated that the total cost of hospitalisation was almost 50% lower for 115 lower respiratory tract infection patients who were managed according to protocol recommendations than for 112 patients who were managed before protocol implementation (£1,020 [e. 1,615] versus £2,024 [e3,204] per patient respectively). Key factors were reduced length of stay and a shorter duration of parenteral antibiotic therapy.(23) Similar results have been found in other studies.(24,25)
One of the main elements in reducing the costs of antimicrobial therapy has been the technique of sequential antibiotic therapy, which is the term used to describe the conversion of parenteral to oral antibiotic treatment (also known as “switch” or “stepdown”).(26) This technique has been shown to be both effective and cost saving.(27)
Antibiotic formulary restrictions and the requirement for written justification on antibiotic stock orders have been demonstrated to improve drug use both from an efficacy and cost standpoint.(28)
The development of C. difficile infection can be clearly associated with the use of third-generation cephalosporins, (29) but has also been linked to a lesser degree with co-amoxiclav utilisation.(30) The incidence of this infection can be reduced by strict application of a restrictive antibiotic policy.(31)
The importance of educating prescribers cannot be overemphasised and is critical to the success of any policy.(32,33) The format of the information provided, for example in the form of a readily accessible laminated pocket-sized card, is also important.(34) This is also where the use of information technology in the form of decision support can be utilised(35); the use of wireless technology with palmtop devices would enable this to be achieved at the bedside.
However, it has been shown that policies are not always effective in reducing antibiotic costs, nor indeed in reducing resistance rates.(36,37) The impact of a policy can also be greatly reduced by the lack of proper introduction and monitoring.(38) Consideration must be given to the links with primary care, to ensure an integrated pathway for antimicrobial use, and also at the interface, for example by the use of a common policy for accident and emergency departments and out-of-hours doctors’ services.
There have been very few novel antimicrobial agents marketed in the last few years, and this dearth is likely to persist until at least 2007.(39) Table 3 shows some of the agents that have recently been launched or are likely to be marketed in the near future. Due to the small number of new agents, it is imperative to optimise the use and minimise the development of resistance to currently available products.
Hospital pharmacists have a major part to play in ensuring that antibiotic prescribing is well controlled. In the UK, the proposal for supplementary pharmacist prescribing will provide excellent opportunities for taking a leading role in this important area.
- 1. Technology. Resistance to antibiotics and other antimicrobial agents. London: The Stationery Office; 1998.
- Standing Medical Advisory Committee. The path of least resistance. London: The Stationery Office; 1998.
- Proposal for a recommendation on the prudent use of antimicrobial agents in human medicine. European Union; 2001. SAN 134.
- Antimicrobial resistance action plan 2002–2005. Belfast: Department of Health, Social Services and Public Safety; 2002.
- Subgroup of the Scientific Advisory Committee of the National Disease Surveillance Centre. A strategy for the control of antimicrobial resistance in Ireland. Dublin, 2001.
- McElnay JC, Scott MG, Sidara JY, et al. Pharm World Sci 1995;17:207-13.
- Audit Commission for Local Authorities and the National Health Service in England and Wales. A spoonful of sugar. London: Audit Commission; 2001.
- Smith DW. Pharmacotherapy 1999;19:129-32.
- Woodford N, Johnson AP, Morrison D, et al. Clin Microbial Dev 1995;8:585-615.
- Stosor V, Peterson LR, Postelnick M, et al. Arch Intern Med 1998;158:522-7.
- Communicable Disease Surveillance Centre. Clostridium difficile in England and Wales: a quarterly report. Commun Dis Rep Wkly 1998;8:15.
- Wilcox MH, Cunniffe JG, Trundle C, et al. J Hosp Infect 1996;34:23-30.
- Al-Eidan FA, McElnay JC, Scott MG, et al. J Clin Pharmacol Ther 2000;21:101-9.
- Working Party of British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 1994;34:21-42.
- Schleas DM, Gerding DN, John JF, et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the prevention of antimicrobial resistance. Clin Infect Dis 1997;25:584-99.
- Murray MD, Kohler RB, McCarthy MC, et al. Am J Hosp Pharm 1988;45:584-8.
- Seppala H, Klaukka T, Vuopio-Varkila J, et al, and the Finnish Study Group for Antimicrobial Resistance. New Engl J Med 1997;337:441-6.
- Saez-Llorens X, Castrejonde Wong MM, Castano E. Paediatr Infect Dis J 2000;19:200-6.
- Belonga EA, Schwartz B. BMJ 1998;317:668-75.
- Stuelens MJ. BMJ 1998;317:652-4.
- Schoenbaum SC. HMO Pract 1993;7:5-11.
- Grimshaw JM, Russell IT. Lancet 1993;342:317-22.
- Al-Eidan FA, McElnay JC, Scott MG, et al. J Antimicrob Chemother 2000;45:387-94.
- Nathwani D, Rubenstein E, Barlow G, et al. Clin Infect Dis 2001;32:728-41.
- Hailey HJ. Am J Health System Pharm 2000;57 Suppl 3:17-21.
- Leleks M, Gould IM. J Hosp Infect 2001;48:249-57.
- Al-Eidan FA, McElnay JC, Scott MG, et al. J Antimicrob Chemother 1999;44:709-15.
- Thuong M. J Antimicrob Chemother 2000;46:501-8.
- De Lalla F, Privilera G, Ortisi G, et al. J Antimicrob Chemother 1989;23:623-31.
- Bignardi GE. J Hosp Infect 1998;40:1-15.
- Cooke RPD, Binyon D, Goddard SV. Hosp Pharm 2000;7:52-4.
- MacDonald J, Ferguson J. Aust Prescriber 2001;24:32.
- Soumerai S, Avorn J. JAMA 1990;263:549-56.
- Levy A, Campbell D, Spencer R, et al. BMJ 2000;321:384.
- Evans RS, Pestotnik SL, Classen DC, et al. N Engl J Med 1998;338:232-8.
- Gould IM, Jappy B. J Antimicrob Chemother 1998;38:895-904.
- Morgan AS, Brennan PJ, Fishman NU. Ann Pharmacother 1997;31:970-3.
- Burnett KM, Scott MG, Kearney MP, et al. Pharm World Sci2002; (in press).
- Poste G. Pharma Times 1999; April:32-4.