Trends in hospital antimicrobial prescribing after 9 years of stewardship

I. M. Goulda,* and B. Jappyb

Departments of a Microbiology and b Pharmacy, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, Scotland, UK

Abstract

Trends in antibiotic prescribing in Grampian have been monitored prospectively for 11 years from 1986 using computerized ward stock lists and laboratory data relating to all in-patient and out-patient treatments in all Grampian hospitals. The main outcome measures were the number of antibiotics available for routine and restricted use, annual expenditure and defined daily doses (DDDs) of high expenditure antimicrobial agents. An antibiotic committee introduced a policy and formulary in the third year of the study which has had only limited success in controlling prescribing. This report updates the audit from 1992/3 to 1996/7. During this period 22 new antibiotics were considered for inclusion in the hospital formulary. Seventeen, including seven antiretroviral agents, were incorporated, all for restricted use only. Despite this, expenditure on antibiotics has more than trebled since 1986/7 and increased 50% since 1992/3, two-thirds of the latter increase being due to the use of new drugs, namely anti-HIV drugs, lipid amphotericin derivatives and teicoplanin. Big increases in the use of co-amoxiclav, acyclovir, ciprofloxacin and cefotaxime account for the remainder of the increased expenditure. There was an overall increase of 16.9% in DDDs between 1992/3 and 96/7 to 424.0 DDDs/1000 patient days (393.4 DDDs for antibacterials). These findings highlight the current difficulty in controlling prescribing budgets, the increasing use of antibiotics and the consequent increase of antimicrobial-resistant microorganisms.

Introduction

There is increasing concern about antibiotic resistance both in the UK and elsewhere. Recent reports13 have emphasized the large amount of antibiotics used both in general practice and in animal husbandry and the likely relationship of this to increasing resistance problems in pathogens such as Salmonella and Campylobacter spp. and primary community pathogens such as pneumococci. About 90% of all antibiotics are consumed in the community. The remaining 10% are used in hospitals but while only a relatively small amount, it is important in terms of cost and is considered by some to be more important in the proliferation of multiply resistant organisms than community consumption.4

Despite the need for information, there is very little published data on hospital antibiotic consumption in the UK.1 Shared concerns about increasing costs of pharmacy budgets and antibiotic resistance have led us to monitor antibiotic usage in all Grampian hospitals over the past 11 years. This report updates that previously published on data from 1986–1993.5 We are unaware of any similar data published from other UK hospitals.

Materials and methods

Data on antibiotic consumption, expressed as defined daily doses (DDDs) were obtained from the pharmacy computer (PCSIS). Ward pharmacists and clinical microbiologists operated a collaborative advisory service with daily ward rounds and round the clock advice on prescribing. The antibiotic policy, originally introduced in 1988, was updated in 1991 and a further update became part of a joint hospital– GP formulary in 1995. There is an active programme of audit57 and educational meetings on various aspects of antibiotic prescribing. Grampian is a geographically diverse region in north-east Scotland with a relatively young, affluent population of 540000. There is one large acute tertiary referral/teaching hospital of 1384 beds in Aberdeen. In addition there is a small district general hospital of 190 beds in Elgin, one large long-stay hospital for the elderly of 332 beds, several small community hospitals and two psychiatric hospitals. Susceptibility data were taken from data generated routinely in the clinical diagnostic laboratory by Stokes’ method and do not exclude repeat isolates.

Results

Since 1992/3, 22 new antibiotics have been considered for inclusion in the hospital formulary but only 17 were approved, all for restricted use. Total antimicrobial expenditure now exceeds £1.5 million, the largest increases being due to new drugs, namely anti-HIV agents, new amphotericin formulations and teicoplanin, which account for approximately two-thirds of the increased costs since 1992/3.

Table IGo shows the increases in total drug and antibiotic costs for the region and a trebling of antibiotic costs in the decade. Table IIGo shows the changes in patient activity over the same period in Aberdeen Royal Infirmary which accounts for over 85% of the total antibiotic prescribing costs.


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Table I. Drug expenditure in Grampian
 

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Table II. In-patient statistics at Aberdeen Royal Infirmary
 
Anti-HIV reverse transcriptase and protease inhibitors have only recently been approved (1997) for inclusion in the formulary (Table IIIGo) following the publication of convincing evidence of their efficacy.8 Expenditure on anti-HIV drugs was £112000 in 1996/7. Azithromycin was included as a single dose treatment for Chlamydia-related urethritis. Clarithromycin replaced all iv erythromycin use because there were no cost implications but its use in oral form was restricted owing to higher cost. Tazobactam/ piperacillin has completely replaced piperacillin, again because there were no financial implications. Ceftriaxone has been added for out-patient iv therapy and meropenem for highly resistant Gram-negative infections including neonatal meningitis.


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Table III. Antibiotics considered for addition to the hospital formulary 1992–1997a
 
Table IVGo highlights the increasing use of cefotaxime and shows a similar situation for co-amoxiclav, flucloxacillin, ciprofloxacin and acyclovir. Increased use of these five agents accounts for approximately 30% of the increased expenditure since 1992/3. Table VGo shows selected susceptibility data on key Gram-negative isolates.


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Table IV. Change in use of approved high-expenditure antimicrobial agents (Grampian Hospitals 1992/3–1996/7)a
 

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Table V. Selected antibiotic susceptibilities for 1996 (percentage sensitive)
 
Audits

Several audits carried out during the period described have been detailed elsewhere.6,7 As part of a thesis a clinical pharmacist introduced diagnostic and therapeutic protocols in one hospital for respiratory and urinary tract infection. These were associated with significant improvement in appropriateness of empirical treatment, and a decrease in non-formulary use of antibiotics, costs and average duration of treatment.9

Discussion

Compared with our previous study5 there is one encouraging sign. Use of the older agents is being reduced (cefuroxime, cephradine, amoxycillin, penicillin, erythromycin, metronidazole and vancomycin) but this is more than offset by huge increases in the use of co-amoxiclav, cefotaxime, flucloxacillin, ciprofloxacin and to a lesser extent teicoplanin. Control of a large outbreak of an SHV-2-producing Klebsiella pneumoniae10 has led to a marked and persistent reduction in the use of cefotaxime and ceftazidime on the ICU (unpublished data) and in the use of cefotaxime and cefuroxime for perioperative prophylaxis (replaced by co-amoxiclav, data not shown). However, the overall use of cefotaxime has increased markedly from an already high level and is the subject of current audit. Reasons for its high use historically are unclear but may be related to discount prices and a tradition of using it in preference to cefuroxime. In view of the high use of broad spectrum ß-lactams, the low rate of infections with Clostridium difficile is surprising. The number of cases remained fairly static over the period at approximately 100 per annum (unpublished).

Antibiotic costs have increased substantially (50% in the past 4 years to approximately £1.5 million) but have remained at approximately 18% of the overall drug budget. In 1986 they were 11.9% of the budget.

Our major resistance problems have been an ESBLpositive outbreak of K. pneumoniae,10 third-generation cephalosporin (3GC) and 4-fluoroquinolone (4-FQ) resistance in inducible Gram-negatives11 (Table VGo) and a carbapenem-resistant K. pneumoniae.12 Methicillin-resistant Staphylococcus aureus had not yet become a problem in Grampian at the end of the period of this study (March 1997), so it is difficult to explain the increased use of teicoplanin other than as a replacement for vancomycin and a tendency to use higher doses.

Control of antibiotic use remains problematic. Conventional control measures13,14 are having only a limited effect on controlling escalating antibiotic prescribing. New initiatives are urgently needed. Modern medicine is a victim of its own success, with increasing numbers of diagnostic and therapeutic procedures further immunosuppressing patients, making them more susceptible to infection.15 Increased pressure on beds causing more rapid turnover of patients may increase the empirical use of antibiotics. An oral switch policy is reducing the amount of iv use with some cost savings, if not any reduction in DDDs.57,16 While ciprofloxacin use continues to escalate, we have maintained a high proportion of oral use since an educational campaign in 1989.6

Our audits on length of therapy and number of patients treated with combinations are similar to other published studies.6,7,16 We believe that automatic discontinuation of empirical therapy should be considered where therapy is continued unintentionally, but no agreement has been reached on the required redesign of the drug Kardex. Previous audits have shown success in shortening the duration of surgical prophylaxis6,7 and guidelines for implementation of single dose surgical prophylaxis are being followed.4

We have no information on whether doses used are comparable with previous years, but the 1995 edition of our joint Grampian formulary now has detailed dose guidance. Certainly, the initial dosing recommendations of manufacturers for certain drugs such as ciprofloxacin and teicoplanin were modified in 1995 and this is likely to have led to increases in the mean dose given. Fears of litigation encouraging excessive empirical prescribing are also cited as a cause of increased prescribing.6

Our audits of the level of use of the laboratory, turnaround times and speed of reporting suggest similar results to the literature but there did seem to be poor awareness of the policy.6,7 If the policy was followed, duration of treatment was reduced. We (unpublished data) and others17 have confirmed this reduction in audits of treatment of bacteraemia. However, two audits have shown that the stopping of unnecessary antibiotics is missed in over half of cases after culture and susceptibility results are available.6,7

That others are having problems in containing prescribing is well described in the literature.4 Our results suggest that improving awareness of the policy by education is important.6,7 While a previous audit suggested reasonable adherence to a restricted list,5 this was removed in 1995. A recent study from the USA18 suggests that it would be worth reinstating. Limited data available from elsewhere suggest tremendous variations in use and resistance19,20 and comparison of control measures may be useful to identify those that are more successful. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) has recently formed a study group for this purpose.7

There is a limit to what can be accomplished without dedicated resources for audit and multi-disciplinary antibiotic teams as recommended in the Copenhagen Declaration.21 Audit will be easier when computerized prescribing is available, but this seems some years away.22 Introduction of clinical guidelines in key areas of overuse of antibiotics such as post-operative fever and surgical antibiotic prophylaxis may help. In the meantime, there is no easy answer to containment of escalating prescribing.

Acknowledgments

Thanks are due for the continued support from colleagues and members of the Antibiotic and Formulary Committees for their help in collecting the data presented.

Notes

* Corresponding author. Fax: +44-1224-840632; E-mail: i.m.gould{at}abdn.co.uk Back

References

1 . House of Lords Select Committee on Science and Technology Report. Resistance to Antibiotics and Other Antimicrobial Agents. The Stationery Office. Session 1997–98, 7th Report.

2 . World Health Organization. (1997). The medical impact of the use of antimicrobials in food animals. Report of a WHO meeting, Berlin, Germany, 1997; 13–17 WHO/EMC/ZOO/97.4. WHO, Geneva.

3 . World Health Organization. (1997). The current status of antimicrobial resistance in Europe. Report of a WHO workshop held in collaboration with the Italian Associazione Culturale Microbiologia Medica Verona, Italy, 12 December 1997; WHO/EMC/BAC/ 98.1.WHO, Geneva.

4 . McGowan, J. E. (1994). Do intensive hospital antibiotic control programs prevent the spread of antibiotic resistance? Infection Control and Hospital Epidemiology 15, 478–83.[ISI][Medline]

5 . Gould, I. M. & Jappy, B. (1996). Trends in hospital antibiotic prescribing after introduction of an antibiotic policy. Journal of Antimicrobial Chemotherapy 38, 895–904.[Abstract]

6 . Gould, I. M. (1996). Hospital antibiotic use and its control—the UK experience. In Du Bon Usage Des Antibiotiques à l’Hôpital, (Wolff, M., Crémieux, A. C., Carbon, C., Vachon, F., Coulaud, J. P. & Vildé, J. L., Eds), pp. 107–19. Arnette Blackwell.

7 . Gould, I. M. (1999). Stewardship of antibiotic use and resistance surveillance—the international scene. Journal of Hospital Infection 43, S253–60.[ISI][Medline]

8 . Cooper, D. A. & Emery, S. (1998). Therapeutic strategies for HIV infections—time to think hard. New England Journal of Medicine 339, 1319–21.[Free Full Text]

9 . McCaig, D. J., Hinde, C. A., Downie, G. & Wilkinson, S. (1999). Antibiotic use in elderly in-patients before and after introduction of treatment guidelines. International Journal of Pharmacy Practice 7, 18–28.

10 . Hobson, R. P., MacKenzie, F. M. & Gould, I. M. (1996). An outbreak of multiply-resistant Klebsiella pneumoniae in the Grampian region of Scotland. Journal of Hospital Infection 33, 249–62.[ISI][Medline]

11 . Wagenlehner, F., Forbes, K., MacKenzie, F. M. & Gould, I. M. (1999). Molecular epidemiology and antibiotic resistance of Enterobacter spp. from four distinct nosocomial and community populations in Grampian, UK. In Proceedings of the Twenty-First International Congress of Chemotherapy, Birmingham, UK, 1999. Abstract 61.

12 . MacKenzie, F. M., Forbes, K. J., Dorai-John, T., Amyes, S. G. B. & Gould, I. M. (1997). Emergence of a carbapenem resistant Klebsiella pneumoniae. Lancet 350, 783.[ISI][Medline]

13 . Working Party of the British Society for Antimicrobial Chemotherapy Report. (1994). Hospital antibiotic control measures in the UK. Journal of Antimicrobial Chemotherapy 34, 21–42.[Abstract]

14 . Goldmann, D. A., Weinstein, R. A., Wenzel, R. P., Tablan, O. C., Duma, R. J., Gaynes, R. P. et al. (1996). Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. Journal of the American Medical Association 275, 234–40.[Abstract]

15 . Krcmery, V. & Gould, I. M. (1999). Antibiotic policies in Central/ Eastern Europe (CEE) after 1990. Journal of Hospital Infection 43, 267–74.

16 . Laing, R. B. S., MacKenzie, A. R., Shaw, H., Gould, I. M. & Douglas, J. G. (1998). The effect of intravenous-to-oral switch guidelines on the use of parenteral antimicrobials in medical wards. Journal of Antimicrobial Chemotherapy 42, 107–11.[Abstract]

17 . Cunney, R. J., McNamara, E. B., Alansari, N., Loo, B. & Smyth, E. G. (1997). The impact of blood culture reporting and clinical liaison on the empiric treatment of bacteraemia. Journal of Clinical Pathology 50, 1010–12.[Abstract]

18 . White, A. C., Jr, Atmar, R. L., Wilson, J., Cate, T. R., Stager, C. E. & Greenberg, S. B. (1997). Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities and clinical outcomes. Clinical Infectious Diseases 25, 230–9.[ISI][Medline]

19 . Natsch, S., Hekster, Y. A., de Jong, R., Heerdink, E. R., Herings, R. M. C. & van der Meer, J. W. M. (1998). Application of the ATC/DDD methodology to monitor antibiotic drug use. European Journal of Clinical Microbiology and Infectious Diseases 17, 20–4.[ISI][Medline]

20 . Felmingham, D. & Washington, J. (1999). Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens—findings of the Alexander Project 1992–1996. Journal of Chemotherapy 11, 5–21.

21 . Danish Ministry of Health, Food, Agriculture and Fisheries. (1998). The Microbial Threat (The Copenhagen Recommendations). pp. 1–4. Ministry of Health, Copenhagen, Denmark.

22 . Evan, R. S., Pestotnik, S. L., Classen, D. C., Clemmer, T. P., Weaver, L. K., Orme, J. F., Jr et al. (1998). A computer-assisted management program for antibiotic and other antiinfective agents. New England Journal of Medicine 338, 232–8.[Abstract/Free Full Text]

Received 15 July 1999; returned 15 October 1999; revised 17 December 1999; accepted 10 January 2000





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