Impact of an interdisciplinary strategy on antibiotic use: a prospective controlled study in three hospitals

V. von Gunten1,*, N. Troillet2, J. Beney1, K. Boubaker2, J.-C. Lüthi3, P. Taffé4 and J.-P. Reymond1

1 Division of Pharmacy, Central Institute of the Valais Hospitals, Sion; 2 Centre for Infectious Diseases and Epidemiology, Central Institute of the Valais Hospitals, Sion; 3 Valais Health Observatory, Sion; 4 Centre d'épidémiologie clinique, Institut Universitaire de Médecine Sociale et Préventive, Lausanne, Switzerland


* Corresponding author. Present address: Pharmacy Department, Children's & Women's Health Centre of British Columbia, 4480 Oak Street, Vancouver, BC, V6H 3N1, Canada. Tel: +1-604-875-2059; Fax: +1-604-875-3735; Email: vvongntn{at}interchange.ubc.ca

Received 16 August 2004; returned 27 September 2004; revised 23 November 2004; accepted 15 December 2004


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Objectives: Evaluation of the impact of the implementation of practice guidelines, with or without their reinforcement by a pharmacist, on the intra-hospital use of antibiotics.

Materials and methods: The duration of antibiotic treatment, their cost, and the length of patient stay were compared in three secondary-care hospitals, before and after interventions that were designed to promote rational antibiotic use. After randomization, hospital A received no intervention (control), local practice guidelines were implemented in hospital B (low grade intervention), and these guidelines were reinforced by a clinical pharmacist in hospital C (high grade intervention). Adherence to the guidelines was measured in hospitals B and C. Multivariable statistical analyses were carried out to adjust for confounding factors.

Results: None of the outcomes measured in the 1200 included patients decreased between the two study periods in any hospital. Hospital A was significantly and independently associated with an increase in the duration of antibiotic treatments, the cost of antibiotics (acquisition and global costs), and the length of stay. Although these differences were not statistically significant, increases in hospital B were higher than in hospital C. Adherence to guidelines was significantly higher in hospital C.

Conclusions: Even though interdisciplinary interventions aiming at rationalizing antibiotic use could not diminish the duration of treatments, their costs or the length of stay, they proved useful to control the progression of these parameters.

Keywords: practice guidelines , antibiotic use , costs , interdisciplinary team , pharmaceutical services


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Antibiotics represent approximately 30% of acute care hospitals' drug expenditures; they are prescribed for 20–50% of inpatients, and contribute to the emergence of resistant microorganisms. Surveys have shown that 22–65% of antibiotic prescriptions are either inappropriate or incorrect.1 Indeed, several organizations have written action plans to control the costs of antibiotics and limit their selective pressure on resistant microorganisms through surveillance and interventions promoting their rational use. Every health care professional, including pharmacists, may play an important role in these efforts.2

Different interventions have been described to guide a more appropriate and cost-effective use of antibiotics in hospitals: some are restrictive (automatic stop orders, restricted antibiotic list, mandatory approval by infectious diseases specialists). Others focus on education (face-to-face discussion, conferences, distribution of printed material, audit with feed-back), or are based on tools to help physicians in their decision making (practice guidelines, computer programs). The importance of combining strategies to enhance the success of any intervention has been emphasized.3 Clinical practice guidelines are used to promote the rational use of antibiotics. They need to be adequately prepared, implemented and supported to have a positive impact.4 Several studies support the role of the clinical pharmacist as a drug therapy advisor in institutional settings,5 fewer demonstrate his/her impact on quality or cost in the implementation of antibiotic guidelines.6

The aim of this controlled ‘before–after’ study was to evaluate the impact of the implementation of local practice guidelines, with and without their reinforcement by a clinical pharmacist, on the intra-hospital use of antibiotics.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Setting and study design

The general medical wards and intensive care units of three comparable secondary-care non-university affiliated public hospitals in western Switzerland (100–120 acute-care beds each, 5000–6000 admissions per year each, and similar case-mix indexes) were studied during two 6 month periods (November 2001 to April 2002 and November 2002 to April 2003). Over each period of time, the first 200 patients admitted to these wards of each hospital were enrolled into the study provided they received antibiotic therapy. Hospitals were randomly assigned to no intervention (hospital A, control), implementation of guidelines only (hospital B, low grade intervention), or implementation of guidelines with their reinforcement by a clinical pharmacist (hospital C, high grade intervention). Local practice guidelines, based on published recommendations, a common drug formulary, and regional antibiotic susceptibility patterns, were developed and implemented in hospitals B and C between the two study periods by infectious diseases physicians, pharmacists, and the heads of internal medicine of these two hospitals. In hospital C, a clinical pharmacist reviewed the medical charts and participated in clinical rounds twice weekly during the intervention period. She informed the physicians on any deviation from the guidelines, necessity to adjust dosages, and possibilities to narrow the spectrum of activity of antibiotics or to switch to oral therapy.

Data collection

Data were collected from the medical charts. The outcome variables were the length of hospital stay, the duration of the antibiotic treatment (distinguishing oral and intravenous administrations), and costs expressed as the cost of the substances and the global cost of treatment including substances, devices, and nursing time for the administration of the treatment. The adherence to guidelines in the second study period was evaluated, in hospitals B and C, by a blinded investigator.

Other collected variables included the age, the gender, the Charlson comorbidity index, microbiological results, the antibiotics used, their indication, dosage and route of administration.

Statistical analysis

Proportions and medians were compared between hospitals and study periods in univariate analysis by using {chi}2, Fisher's exact, Kruskal–Wallis or Mann–Whitney tests, as appropriate.

After exclusion of outliers based on the inspection of histograms and clinical appraisal, multivariable models were developed to obtain adjusted outcome comparisons between hospitals and study periods. Independent variables in the final models included the dummy-coded hospitals and study periods, and confounding factors remaining after a backward selection from the following variables: age, gender, Charlson comorbidity index, nosocomial infection, difficult-to-treat infection and difficult-to-treat pathogen, as defined in Table 1. P values were two-tailed; P ≤ 0.05 was considered to be significant.


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Table 1. Patients' characteristics in the intervention and control hospitals during the pre- and post-intervention periods

 

    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The characteristics of the 1200 included patients are shown in Table 1. Significant differences were found only for the proportion of patients with no comorbidities which was higher in hospital A in the pre-intervention period, and for the proportion of patients suffering from nosocomial infections which was higher in hospital C in the post-intervention period.

Inter-hospital differences were however present in the baseline values of the measured outcomes. Hospital A (control) had lower median values for the total duration of antibiotic treatments (P < 0.001), costs of antibiotics (P=0.003), global costs of antimicrobial treatments (P < 0.001), and length of stay (P=0.003).

No decrease in the outcomes as defined in Table 2 was observed in any of the participating hospitals. However, significant increases were found only in hospital A (control) when comparing it with the two other participating institutions while adjusting for any potential changes in the patients' characteristics between the two study periods. Moreover, although the differences were not statistically significant, the observed increases in the parameters investigated were higher in hospital B (low grade intervention) than in hospital C (high grade intervention).


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Table 2. Durations of treatment, costs, and length of stay in the intervention and control hospitals during the pre-intervention (PRE) and post-intervention (POST) periods

 
During the post-intervention period, 95/170 patients (56%) in hospital B and 122/170 (72%) in hospital C were treated in accordance to the guidelines (P=0.002). Thirty patients in each hospital were excluded because their indication to receive antibiotics was unclear or not included in the guidelines.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In a previous study, Gums et al.7 attributed a decrease in the length of patients' stay to antibiotic control programmes including consultations by multidisciplinary teams. In this study, the implementation of practice guidelines by infectious disease consultants, pharmacists, and in-house physicians, with or without their reinforcement by a clinical pharmacist, was not associated with any decrease in the duration of hospital antibiotic treatments, their costs, or the length of patients' stays. However, a significant increase in the parameters investigated was observed only in the control hospital, compared with the hospitals which benefited from an intervention. Moreover, although these differences were not statistically significant in the intervention groups, the observed increases were higher in the hospital with a low grade intervention than in the hospital with a high grade intervention. The impact of the high grade intervention, which included the reinforcement of the guidelines by a clinical pharmacist, is demonstrated by a higher adherence to the guidelines (72%), compared with 56% in the hospital without reinforcement or to published rates of 40–60%.8 These results suggest a positive effect of the implementation of practice guidelines for antibiotic use, particularly when they are reinforced by a clinical pharmacist, thus arguing in favour of multifaceted interventions and confirming the results of previous studies that demonstrated the lack of efficacy of the distribution guidelines, in the absence of additional measures.9

This study used a prospective, controlled, ‘before–after’ design. The same months were chosen for each observation period to avoid seasonal biases. The different interventions were randomly allocated to different hospitals to avoid contamination biases. These institutions were similar in terms of size, activities, and case-mix indexes, thus minimizing the risk of inappropriate comparisons. In addition, the multivariable analyses took potential confounding factors into account, allowing us to estimate the independent association of each of the interventions with the measured outcomes.

Nevertheless, the control hospital had significantly lower baseline durations of antibiotic treatments, costs and length of stays than the others. In addition, although these parameters increased significantly in this hospital between the two study periods, they remained lower than in the others. As discussed by Avorn & Solomon,10 many factors, other than the patients' characteristics or their type of infection, may influence antibiotic use. Such factors that may be cultural or economical, are difficult to capture in a study on antibiotic use and could have played an unseen role in our results. Other limitations of this study suggest caution while interpreting its results. First, outcomes such as mortality, resistance rates to antibiotics or quality of care were not assessed and may vary independently from the costs, the duration of treatments or the length of stay. Second, this study addressed only in-hospital antibiotic use and did not include the treatments of patients transferred or discharged on antibiotics. Third, it was not designed to determine the cost-effectiveness of the implemented interventions.

In conclusion, this study illustrates the difficulties encountered when measuring the impact of interventions to promote the rational use of antibiotics. Nevertheless, it suggests a positive impact of the development and implementation of local guidelines, particularly when they are reinforced by a clinical pharmacist.


    Acknowledgements
 
We thank J. Charvat, B. Haldimann, J.-C. Métrailler, J. Petite, M. Schmid and P.-Y. Uldry, the heads of medicine in the participating hospitals, for their commitment.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Ansari, F., Gray, K., Nathwani, D. et al. (2003). Outcomes of an intervention to improve hospital antibiotic prescribing: interrupted time series with segmented regression analysis. Journal of Antimicrobial Chemotherapy 52, 842–8.[Abstract/Free Full Text]

2 . Knox, K., Lawson, W., Dean, B. et al. (2003). Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist—a UK perspective. Journal of Hospital Infection 53, 85–90.[CrossRef][ISI][Medline]

3 . Bero, L. A., Grilli, R., Grimshaw, J. M. et al. (1998). Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. The Cochrane Effective Practice and Organization of Care Review Group. British Medical Journal 317, 465–8.[Free Full Text]

4 . Moulding, N. T., Silagy, C. A. & Weller, D. P. (1999). A framework for effective management of change in clinical practice: dissemination and implementation of clinical practice guidelines. Quality in Health Care 8, 177–83.[Abstract]

5 . Schentag, J. J., Ballow, C. H., Fritz, A. L. et al. (1993). Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory. Diagnostic Microbiology and Infectious Disease 16, 255–64.[CrossRef][ISI][Medline]

6 . Martinez, M. J., Freire, A., Castro, I. et al. (2000). Clinical and economic impact of a pharmacist—intervention to promote sequential intravenous to oral clindamycin conversion. Pharmacy World and Science 22, 53–8.[CrossRef][Medline]

7 . Gums, J. G., Yancey, R. W., Jr, Hamilton, C. A. et al. (1999). A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Pharmacotherapy 19, 1369–77.[ISI][Medline]

8 . Halm, E. A., Atlas, S. J., Borowsky, L. H. et al. (2000). Understanding physician adherence with a pneumonia practice guideline: effects of patient, system, and physician factors. Archives of Internal Medicine 160, 98–104.[Abstract/Free Full Text]

9 . Brown, E. M. (2002). Guidelines for antibiotic usage in hospitals. Journal of Antimicrobial Chemotherapy 49, 587–92.[Free Full Text]

10 . Avorn, J. & Solomon, D. H. (2000). Cultural and economic factors that (mis)shape antibiotic use: the nonpharmacologic basis of therapeutics. Annals of Internal Medicine 133, 128–35.[Abstract/Free Full Text]





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