1. MULTI-CENTER INDICATOR INTERVENTION RESEARCH ON SURGICAL PHROPHYLAXIS IN 2 HOSPITALS IN PEOPLE’S REPUBLIC OF CHINA Wang Qing 1, Wang Yuqin 2, Edelisa D.Carandang 3, Dennis Ross-degnan 4, Tang Jingbo 5 1 Center for Drug Reevaluation of State Drug Administration, P.R.China 2 Xuanwu Hospital of the Capital University of Medical Sciences, P.R.China 3 Action Programme on Essential Drugs, WHO, Geneva, Switzerland 4, Harvard Medical School and Harvard Pilgrim Health Care, Boston, USA 5. Liuhuaqiao Hospital, Guangzhou, P.R.China

2. ABSTRACT OBJECTIVE Through the intervention and comparison study of rational antibiotics use in perisurgical period, we want to explore a set of scientific evaluation and intervention methods which are fit for China's situation, and promote the development of rational drug use in China. METHODS Selected two third level general hospitals and separated them into intervention hospital and control hospital. Gave intervention to the intervention hospital from February 2001 to August 2001, and carried out the comparison research on the same period of inpatient surgical cases of thryroidectomy, mastectomy, cholescystectomy, and hysteromyomectomy +appendix from 2000 to 2002. RESULTS The average antibiotics expenditure was cut down from 740.20 RMB to 352.03 RMB (P<0.01) in intervention hospital from 2000 to 2001, but went back to 494.62 RMB in 2002. There was a remarkable improvement on the rationality of antibiotics use in intervention hospital during the intervention approaches implemented, but the situation went back after the intervention stopped. The rationality percentages in intervention hospital are from 22.88% to 80.33% and to 20.66%. Meanwhile, there is no difference on the rationality of control hospital. CONCLUTION: It is practicable and effective to implement the rational drug use intervention in the research, and they play active roles on promoting safely, effectively and economic antibiotic use in China. Te follow-up study in 2002 also showed that the work for promoting rational drug use is a long-term task. The intervention should be going on to keep the prescriber’s good practice.

3. BACKGROUND INTRODUCTION From 2001 to 2002, the first systematic multi-center rational drug use (RDU) research in China was carried out by Center for Drug Reevaluation of State Drug Administration and Xuanwu Hospital Group. The research got the financial and technical support from WHO/EDM. This antibiotic prophylaxis intervention study was the main part of this research. BACKGROUND In both the developed and the developing world, medically inappropriate, ineffective, and economically inefficient use of pharmaceuticals commonly occurs in health care facilities. In China, self-medication, polypharmacy, overuse of antibiotics and injections are easy to be observed. In 2001, a national pharmaceutical situation survey in four cities of China was conducted by MOH and SDA of China. The survey was focused on the information of people’s access to essential drugs and drug safety, efficaciousness, quality and reliability as well as the proper utilization of them. 26 hospitals, 21 drug outlets, and 4 drug warehouses were included in the survey. The results showed that irrational drug use in these four cities is popular, especially the percentages of antibiotic and injection use are 47.82% and 35.13% respectively. In the treatment of non-pneumonia--acute respiratory tract infection in outpatients among 26 hospitals, the percentage of antibiotics use is 83.5%, antipyretic/analgesic 37.7%, cough and/or cold drugs 62.7% and other drugs 48.8%. After level I assessment, the proper handlings are only 16.5% and the improper ones are as high as 83.5%. After level II assessment, the proper handlings are 46.5% and the improper ones are 53.5%.

4. BACKGROUND Inappropriate antibiotic use increases costs and the risks of antibiotic resistance. Around 50% of top 50 drug expenditures in hospitals in Chinese major metropolis between 1993-1995 were on antibiotics, but only 50% of costs belong to rational use indicators. According to the survey in the Outpatient Department of Beijing Children's Hospital from 1990 to 1993, more than 98% of the patients who were diagnosed with common cold were given antibiotics by physicians, and more than one-third of the patients had been taking antibiotics before coming to the hospital. Using a sensitive Staphylococcus aureus assay, it was found that 70% of blood samples and 43% of cerebrospinal fluid samples from the patients with bacterial meningitis and pneumonia contained antibacterial activity. Bacteria were recovered significantly less often from the samples with antibacterial activity than from those who did not from which antibiotic was not recovered, both in blood (5.3% vs. 12.5%) and in cerebrospinal fluid (2.5% vs. 14.8%). And some previous studies in China had found several problems in the way that antibiotics were used during perisurgical period: incorrect indication for prophylactic use; selection of an inappropriate antibiotic or dosage; initiation of antibiotic therapy several days before surgery without sign of infection; and continuation of therapy for an incorrect length of time, etc. All of these studies indicate that antibiotic abuse is a severe problem in China and that judicious use of antibiotics is urgently needed. In this intervention research, we made efforts to develop and implement agreed guidelines for antimicrobial prophylaxis in surgery with the aim of promoting rational antibiotic use, reducing antibiotic costs. It is common that 50% of hospital revenues from the sale of drugs in China, which can lead to physicians prescribing greater numbers of drugs and more expensive drugs. Irrational drug use has got more and more attention from the public and medical agencies. The work of promoting rational drug use (PRDU) in China was initiated 20 years ago, but all of the researches are separately and no comparison, the methodology applied was not consistent. RDU has not been an important indicator for health unit evaluation now, and also it is still not the key component of national drug policy. Therefore, We look forward to exploring an objective and scientific evaluation and research method to promote the work of RDU in China.

5. MATERIALS AND METHOD All surgical inpatient cases of thryroidectomy, mastectomy, cholescystectomy, and hysteromyomectomy plus appendix from June 1 to July 7, 2000 and 2001in two hospitals and the same period of cases in 2002 of intervention hospital were collected in the study. The data collection form was formulated before baseline data collection. And all contents on the form were recorded in the computer, including the information about patient and admission, information about surgery and antibiotic use, etc. Foxpro6.0 and SPSS 10.0 were used to do the analysis. The prophylaxis guideline was formulated to provide a framework for the intervention, and for the guideline to have maximum effect, we implemented within the intervention hospital in a systematic way using a variety of educational and managerial techniques.

6. INTERVENTION Interventions were focused on promoting rational antibiotic prophylaxis use and reducing antibiotic costs. 1.Education: Training, printed educational materials and face-to-face educational methods are used to different educational targets. ① To doctors and pharmacists: * The antibiotic prophylaxis guideline was formulated and discussed by experts and doctors from different departments of intervention hospital. The process of soliciting suggestions from clinical departments was treated as an important part of guideline development. * Several RDU workshops and seminars were conducted to introduce the RDU knowledge at the beginning and during the research. * Printed RDU materials. For example, "Why and what is the rational drug use?", "The situation of irrational drug use on antibiotics", "The guideline of antibiotics use", "Rational use of antibiotics", etc. * Several sets of reference books were disseminated to every related department of intervention hospital. ② To administrators of hospital The administrators were moved and affected by attending PRDU semiars and many times of face to face reports. Their understanding, supporting and assisting is one of the key factors for the success of the research. 2. Management: ① The formulation of the standard treatment guideline ② Regular meeting of intervention hospital. All members of the study team have meetings at least two times one month. And for the core investigators, there was at least one short meeting one week. ③ Monitor in intervention hospital was appointed to do the inspection. Two monitors in intervention hospital were appointed to do the daily inspection. Whenever the problem happened, the monitor would report to the director of the department, and the director of the department would discuss or communicate with the doctor or pharmacist in the department to handle the problem.

7. Table 1 General information for intervention and control hospital Hospital/Year Intervention HospitalControl Hospital 20002001200220002001 Total cases118122121120 Male1715192216 Female10110710298104 Average age48.3650.2249.248.3248.68 Thryroidectomy3841362932 Mastectomy10 1610 Cholescystectomy3432333432 Hysteromyomectomy + Appendix 363936 39

8. Rationality Intervention HospitalControl Hospital 20002001200220002001 Rational cases37 (31.35%) 112 (91.8%)** 64 (52.88%) 00 Irrational cases81 (68.64%) 10 (8.2%)** 57 (47.12%) 120 (100%) Total118122121120 Incidence of post- surgical infection 00000 Table 2 Rationality comparison for antibiotic prophylaxis use Note: ** p < 0.01

9. Table 3 Irrational antibiotic use analysis in intervention hospital 2000 2001 2002 ProblemsTimes%(/181*)ProblemsTimes %(/200)ProblemsTimes%(/230) Antibiotic use after 3 days of operation 9451.93Incorrect administration route 84.00 Antibiotic use after 3 days of operation 4720.4 Inappropriate antibiotic use 4625.41 Antibiotic use after 3 days of operation 52.50Over dosage4519.6 Incorrect antibiotic use interval 4022.09Others21.00Incorrect administration route 93.9 Over dosage3820.99 Incorrect drug use interval 10.50Inappropriate antibiotic use 73.0 Incorrect administration route 116.07 Incorrect antibiotics combination 41.7 Antibiotic use before 24 hours of operation 21.10 Antibiotic use before 24 hours of operation 20.9 Others21.10

10. Table 4 Comparison of average antibiotic cost in 2000, 2001 and 2002 Hospital/Year Intervention HospitalControl Hospital 200020012002 20002001 Average Antibiotic Cost 740.20352.03**494.621306.31821.82** Variation rate%: 52.4Variation rate%: 37.1 Note:**P<0.01

11. Table 5 Antibiotics used in the intervention hospital 200020012002 Drug NameTimes%Drug NameTimes%Drug NameTimes% 1 Cefuroxime5228.271 Cefuroxime13165.501 Cefuroxime8838.26 2 Others12971.732 Metronidazole3718.502 Metronidazole3213.91 3 Others32163 Others11047.83 Total181100.0 0 Total200100.0 0 Total230100.0 0 Note: Cefuroxime and Metronidazole are two recommended drugs for prophylaxis use in the guideline.

12. RESULTS AND CONCLUSIONS Results From the three-year data analysis, we found that there were significant differences between the intervention and control hospital for the following indicators: rationality of the antibiotic prophylaxis, average antibiotic cost, etc. The differences represented the feasibility and validity of the intervention. The details were showed in the under tables. Conclusions The antibiotic prophylaxis guideline, education and management interventions play active roles on promoting safely, effectively and economic drug use in intervention hospital. Through the successful implementation of this study, we believe that it is also effective and executive to standardize the doctor's practice by formulating and promoting standard treatment guideline and other interventions in China. But the study also showed that promoting rational drug use is a long-term task. National treatment guidelines should be formulated and more researches and interventions should be implemented to make a more rational drug use environment.