JAC Advance Access originally published online on October 31, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):210-213; doi:10.1093/jac/dkm388
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Original research |
Optimizing use of ciprofloxacin: a prospective intervention study
1 Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands 2 Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands
* Corresponding author. Tel: +31-30-6092624; Fax: +31-30-6092429; E-mail: b.van.hees{at}antonius.net
Received 12 June 2007; returned 11 July 2007; revised 23 September 2007; accepted 24 September 2007
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Abstract |
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Objectives: Antimicrobial resistance to ciprofloxacin is increasing. The objective of this study was to reduce the number of inappropriate prescriptions and to improve the quality of ciprofloxacin prescriptions by means of educational intervention.
Methods: In a teaching hospital five units of the Departments of Internal Medicine, Gastro-Enterology, Surgery, Urology and Pulmonary Diseases, selected because of a high rate of ciprofloxacin prescription, participated in a prospective intervention study. The quantity and the quality of prescriptions were reviewed before and after educational intervention and during follow-up. The quality of each ciprofloxacin prescription was independently evaluated by two medical microbiologists. During the intervention period, a medical microbiologist discussed the appropriateness of prescribing ciprofloxacin with prescribing clinicians, and educational presentations were given to clinicians of participating units. Regression analysis was used to analyse trends in time-series data.
Results: The number of ciprofloxacin prescriptions decreased from 81 prescriptions/1000 admissions before intervention to 32 prescriptions/1000 admissions after intervention, a significant reduction of 60.5%. Appropriate prescriptions significantly increased. Significantly fewer inappropriate prescriptions were prescribed after intervention and/or during follow-up. At this time, 23 ciprofloxacin prescriptions/1000 admissions were prescribed, a total reduction of 71.3% compared with baseline.
Conclusions: In a hospital with relatively low baseline ciprofloxacin consumption, intervention by direct consultation of a medical microbiologist and educational presentations led to 3–4-fold sustained reduction in the use of ciprofloxacin and significant improvement in quality of ciprofloxacin prescriptions. Close collaboration between clinicians and medical microbiologists can provide a major contribution to the prudent hospital use of antimicrobial agents.
Keywords: antibiotic prescribing , fluoroquinolones , interventions , quality improvement
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Introduction |
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Fluoroquinolones have excellent in vitro activity against a wide range of both Gram-negative and Gram-positive organisms and can be prescribed orally, with excellent bioavailability. Fluoroquinolones have gained broad acceptance in hospitalized and community patients and their use is increasing.1 Resistance to antibiotics is becoming an increasingly important worldwide problem. Liberal and inappropriate use of antibiotics is considered to be the most important reason for the development of antibiotic resistance.2,3 It has been estimated that up to 50% of antibiotic usage in hospitals is inappropriate.4–8 Reducing the selective pressures of antibiotic usage by judicious antibiotic prescription will prevent or delay the emergence of resistant strains.6,8 In addition, antibiotic resistance to fluoroquinolones is increasing.9,10 Studies have shown that clinical use of fluoroquinolones is an important risk factor for the emergence of resistance in a hospital setting.10
In Europe, significant differences exist in the quantity of antibiotic consumption. The Netherlands has relatively low antibiotic consumption in hospitals.9 This low consumption is, among other reasons, due to close collaboration between clinicians and medical microbiologists. Nevertheless, ciprofloxacin use is also significantly increasing in Dutch hospitals.9 Although the defined daily dose (DDD)/100 bed days at our hospital is below the national average, the use of ciprofloxacin more than doubled from 1996 to 2004 (2.31 DDD/100 bed days to 5.72 DDD/100 bed days, respectively) (Figure 1a). The aim of this study was to evaluate the short- and long-term impact of educational intervention between September 2004 and March 2006, on not only quantitative rates of ciprofloxacin prescription but on the quality of these prescriptions as well.
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Materials and methods |
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Setting
The St Antonius Hospital, Nieuwegein, is a 584-bed Dutch teaching hospital and a tertiary referral centre. The number of annual admissions is over 22 000. This prospective intervention study, with a before and after design, took place in selected units of the Departments of Internal Medicine, Gastro-Enterology, Surgery, Urology and Pulmonary Diseases.
The study was set up as a before and after study. The study comprised three periods and a follow-up: (i) a 3 month pre-intervention observation period (baseline data) from September 2004 to November 2004; (ii) a 3 month intervention period from May 2005 to July 2005; and (iii) a 3 month post-intervention period from September 2005 to November 2005. A 3 month follow-up was performed from January 2006 to March 2006.
Ciprofloxacin use in every hospital nursing unit was analysed quantitatively by calculating the number of prescriptions per 1000 admissions over the period September 2004–November 2004. Units with the highest rates of ciprofloxacin prescriptions were selected for intervention, i.e. the Departments of Urology, Surgery, Internal Medicine, Gastro-Enterology and Pulmonary Diseases. The Department of Haematology uses ciprofloxacin as a component of standard prophylaxis in severely neutropenic patients. For this reason, this ward was not included in this study.
During the two observation periods and follow-up period, all ciprofloxacin prescriptions were registered and reviewed. Clinical and laboratory data were collected to enable accurate assessment of prescribed ciprofloxacin. Prescribers were unaware of the data collection process.
A quality evaluation of each ciprofloxacin prescription before and after intervention was performed by two medical microbiologists (B. M. de J. and M. T.) independently. They placed individual prescriptions into categories using well-defined criteria. We adapted the classification that was developed by Kunin et al. in 197311 and restyled by Gyssens et al.12 to a comprehensive evaluation system. In short, prescriptions can be judged appropriate (category I) or unjustified (category V), or the records can be insufficient for evaluation (category VI). Other prescriptions are placed in categories II, III and IV, indicating inappropriate use; incorrect dose (IIa), incorrect interval (IIb), incorrect route (IIc), duration too long (IIIa), duration too short (IIIb) or better alternative due to higher efficacy (IVa), lower toxicity (IVb), lower cost (IVc) or narrower spectrum (IVd). Inappropriate prescriptions can be allocated to several subcategories at the same time.
During the intervention period, physicians prescribing ciprofloxacin were interviewed by telephone, by a medical microbiologist (for each single ciprofloxacin prescription), to discuss the indication of the use of ciprofloxacin using the guidelines of the hospital antimicrobial committee as a reference. Furthermore educational lectures on the proper use of ciprofloxacin were given to physicians of participating units.
2 tests and Student’s t-tests were applied to establish systematic differences. Agreement between the two independent reviewers was assessed by 
coefficients.13 Regression analysis was used to evaluate trends, as recommended by The Cochrane Effective Practice and Organisation of Care Group (EPOC).5
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Results |
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The patient populations of the first, the third and the follow-up phase were comparable in terms of sex and age. Mean age was 66 years (SD = 14.8), with a range of 21–92 years. Before and after intervention, there was no significant difference in sex and age (P = 0.59 and P = 0.53; respectively).
Quantity of ciprofloxacin prescriptions
A significant increase was observed in ciprofloxacin use before intervention (1996–2004) (Figure 1a) (y = 0.4588x + 1.9858, for slope: 95% CI 0.4–0.5). In 2004 the ciprofloxacin use in our hospital was 5.72 DDD/100 bed days. From September 2004 to November 2004, the general average of ciprofloxacin prescriptions in our hospital was 62 per 1000 admissions. On the five selected wards, the average number of ciprofloxacin prescriptions was 81 per 1000 admissions. In our study period (September 2004 to March 2006), a significant decrease in ciprofloxacin use was demonstrated (Figures 1b and 2a). After intervention there was a trend towards decreasing prescriptions per 1000 admissions, y = –1.6786x + 32.869 (for slope: 95% CI –7.6 to 4.3).
Figure 2(a) shows the number of prescriptions per 1000 admissions before and after intervention as well as in the follow-up period for all selected wards. In the first observation period before intervention, 168 prescriptions (81 prescriptions per 1000 admissions) in total were administered in the selected wards. In the second observation period after intervention, there were 74 prescriptions (32 prescriptions per 1000 admissions) in total, a significant reduction of 60.5% (95% CI 50.6–70.4). The highest reductions after intervention were observed in the Departments of Surgery and Urology (83.9% and 75.6%, respectively). Five months after intervention during follow-up, 58 prescriptions of ciprofloxacin were prescribed (23 prescriptions/1000 admissions), a total significant reduction of 71.3% (95% CI 62.9–79.8) compared with baseline. The highest long-term reduction was observed in the Department of Urology (88.9%). We did not systematically analyse the number of prescriptions of other antibiotics during the study period. In overviews of antibiotic use for the years 2004–2006, we find no evidence for consistent increases in the use of other antibiotics attributable to the restriction of ciprofloxacin use. In particular, consumption of third-generation cephalosporins or carbapenems remained relatively low.
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Clinical indications
For each clinical indication, with the exception of sepsis, there was an absolute decrease in the number of prescriptions. Most of the prescriptions prior to intervention concerned inappropriate prophylaxis (32.1%), mainly for removal of urinary catheters. This indication decreased significantly to 14.9% after intervention to only 1.8% during follow-up (P < 0.01). Only a relative increase was observed for clinical indications, respiratory tract infection and gastrointestinal tract infection (P < 0.05).
Quality of ciprofloxacin prescriptions
Before the intervention, a relevant microbiological investigation was performed in 53.6% of the prescriptions before prescribing ciprofloxacin. After intervention there was a significant increase to 75.7% of prescriptions (P = 0.01, 2).
The agreement between the two independent reviewers during all phases was substantial to a comparable degree ( = 0.62 before intervention versus = 0.68 after intervention versus = 0.54 in the follow-up phase).13 Figure 2(b) shows the effects of the intervention for the two reviewers combined. Three hundred prescriptions were evaluated (categories II, III and IV could be assigned simultaneously to the same prescription). The proportion of non-evaluable prescriptions (category VI) was 5.7%. The proportion of appropriate prescriptions for the two reviewers combined increased significantly (P < 0.05) during follow-up compared with baseline. A significant decrease (P 
0.01) was observed in the number of inappropriate prescriptions (categories II, III and IV) after intervention and/or during follow-up compared with baseline.
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Discussion |
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Compared with national and international standards, the pre-study prescription rate of ciprofloxacin was low in our hospital. Nevertheless, this intervention resulted in a 3–4-fold reduction and a significant improvement in the quality of prescriptions. A possible explanation for the increase in appropriateness of prescriptions might be better adherence to hospital guidelines and the significant increase in microbiological investigation before prescribing ciprofloxacin.
Thirty-two per cent of the prescriptions prior to intervention concerned non-evidence-based prophylaxis for the removal of urinary catheters, an inappropriate indication in our hospital guidelines. During follow-up, only 1.8% of all prescriptions concerned prophylaxis.
A limitation to this intervention study was the lack of control groups. However, in view of the increasing use of ciprofloxacin in our hospital in the years preceding the study period, it is highly unlikely that the substantial decrease observed in this study is due to chance.
We demonstrate a sustained reduction in the use of ciprofloxacin and improvement in the quality of ciprofloxacin prescription, achieved by educational intervention and close collaboration within a hospital between medical microbiologists and clinicians. Given the relatively low baseline consumption of ciprofloxacin in this study it should be worthwhile to adopt this combined approach in other hospital settings.
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Funding |
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No specific funding was received for this study.
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None to declare.
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Acknowledgements |
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We thank Dr James Cohen Stuart and Ellen Tromp for their assistance in the statistical analysis.
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References |
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