ANTIBIOTIC USE IN PATIENTS WITH FEVER OF UNKNOWN ORIGIN (FUO) AT PANTI RAPIH HOSPITAL YOGYAKARTA-INDONESIA Hartayu T 1, Asdie HAH 2, Suryawati S 3 1 Faculty of Pharmacy Sanata Dharma University 2 Department of Internal Medicine and 3 Department of Clinical Pharmacology, Faculty of Medicine Gadjah Mada University, Yogyakarta

ABSTRACT Problem Statement: Antibiotics accounted as the biggest part of drug costs paid by patients admitted to Panti Rapih hospital, and fever of unknown origin (FUO) was the most prominent diagnosis reported. Objectives: To evaluate the pattern of antibiotic use in patients admitted with FUO in Panti Rapih hospital, Indonesia. Design: An explorative study with retrospective quantitative data collection and prospective qualitative data collection. All patients admitted to Panti Rapih Hospital with FUO as diagnosis at admission during the period of December 1996 to June 1997 were selected. Quantitative data were collected to assess the pattern of antibiotic use in FUO and the pattern of diagnosis at both admission and discharge. Qualitative data were collected using in-depth interviews with prescribers and the paramedic chiefs of the wards to explore the reasons for antibiotic use, and identifying final diagnoses. Setting and Population: All patients hospitalized with FUO as diagnosis at admission in Panti Rapih Hospital, during period of December 1996 to June Outcome Measures: Pattern of diagnoses at discharge (final diagnosis), number of antibiotics received, the kind of antibiotics received, the route and administration of antibiotics, average length of stay, range of drug cost during hospitalization, reasons of antibiotic usage. Results: Out of 273 cases analyzed 48 cases (18%) had FUO as final diagnosis, and the rest were diagnosed as having upper respiratory infection 37 cases (14%), dengue fever35 cases (13%), no final diagnosis 18 cases (10%)and others 125 cases (45%). In total 90% of cases used antibiotic, either oral or injection, despite the fact that antibiotic were not recommended for this diagnosis. The average length of stay was 5 days (range:1 day – 9 days). Drug cost varied greatly, with the highest cost observed (US$45.15) being 16 times the lowest (US$ 2.90).Reasons for antibiotic use were generally based on personal or colleagues’ experiences, an assumption of infection despite clinical observation, the absence of a standard treatment for FUO, drug promotion, and negligence in updating information. Conclusions: Antibiotics were used in 90 % of patients with FUO. Efforts should be pursued to reduce the unnecessary use of antibiotics including provision of standard treatment guideline for FUO. Funding Sources: Self Funded.

BACKGROUND  Panti Rapih is a private hospital in Yogyakarta-Indonesia, has 367 beds with 12 specialist departments and 10 subspecialist departments, and has more than 80% Bed Occupation Rate.  Antibiotics accounted as the biggest part of prescription cost and Fever of Unknown Origin (FUO) was the most prominent diagnosis reported.

OBJECTIVES  General To evaluate the pattern of antibiotic use for patients admitted with FUO at Panti Rapih Hospital, Yogyakarta-Indonesia.  Specific To find out: To find out:  The pattern of antibiotics prescribed for FUO  Reasons of antibiotic use  Strategy to improve the appropriateness of antibiotics used in FUO

METHODS  Design:  An explorative study with retrospective quantitative data collection and prospective qualitative data collection.  Setting:  All patients admitted to Panti Rapih hospital with FUO as diagnosis at admission.  Time period of data collection : December 1996 to June 1997  Time period of data collection : December 1996 to June 1997

STUDY DESIGN All patients admitted with FUO in Panti Rapih Hospital Dec ’96- June ‘97 (273 patients) FUO as final diagnosis 48 patients Quantitative data Qualitative Data Observation on prescriptions in medical record In-depth interview with prescribers and chiefs of wards (paramedic) Pattern of Antibiotic use Reason of Antibiotic use Reference: Current Medical Diagnosis and Treatment (Jacobs, 2004): Broad spectrum antibiotic with haematological examination result Reference: Guide to Good Prescribing (WHO,1994) Identify Strategy to Improve the appropriateness of Antibiotic use Other final Diagnoses Upper respiratory infection: 37 patients  Others: 125 patients Dengue fever : 35 patients  No final Diagnosis: 18 patients

Result 1, Diagnosis at hospital discharge NoDiagnosis0-5 (Years old) 5-12 (Years old) >12 (Years old) Total 1FUO (18%) 2Upper respiratory infection (14%) 3Dengue fever (13%) 4Others (45%) 5No final diagnosis (10%) FUO had contributed for 18% of all final diagnoses, and data in reference showed (10-15 %) (Jacobs, 1994)

Result (2),Types of Antibiotic Used in FUO December ‘96 – June ‘97 Patient’s Age (years) Number of patients Types of Antibiotic 0 – 511Erythromycin, Amoxycilin, Ceftriaxone, Cotrimoxazole Cotrimoxazole >1232Amoxycillin, Ampicillin, Chloramphenicol Spyramycin, Ofloxacin, Pefloxacine, Cefixim, Cefetamed, Cefprozil Narrow spectrum antibiotic were used for adults but were not used for children.

Age (years)Number of patients Without antibiotics Recieved 1 or 2 antibiotics 0 – – > Total485 (10%)43 (90%) Result (3), Number of Patients with FUO receiving antibiotic December 1996 – June % patients received 1 or 2 kind of antibiotic before the haematological examination results.

RESULT (4), REASONS OF ANTIBIOTICS USE Reasons of antibiotics use :   An assumption of infection despite clinical observation   Uncertainty of sterilization of hospital environment   Takes too long to wait for laboratory examination results   Modeling personal or colleagues’ experiences   Negligence of updating information   Drug promotion Note: standard guideline for FUO was not available in the hospital

DISCUSSIONS (1)  The data shows that narrow spectrum antibiotic such as Spiramycin and Chloramphenicol were used, despites the fact that narrow spectrum antibiotics are not recommended for FUO.  Jacobs (2004) recommended that broad spectrum antibiotics might be given for FUO patients. Narrow spectrum antibiotic can not be given unless there’s a strong evidence to a specific diagnosis.  The evidence of FUO as the final diagnosis in this hospital (17,6%) was slightly higher than that reported in reference (10 – 15%)( Jacobs, 1994). The factor that might contribut to this phenomenon was insensitivity of diagnosis tools.

Discussion (2)  Among the reasons to use antibiotics in FUO was personal or colleagues’ experiences, eventhough experience is not always reliable. Therefore an agreement to use the reliable reference such as diagnosis guideline and hospital standard treatment guideline are urgently needed.  The drug costs varied widely (US$ 2.90 to US$ 45.15), and factor what might contribute to this result is the unavailability of agreement among prescribers in this hospital on which drug and which brand name should be selected for FUO.

CONCLUSIONS  Narrow spectrum antibiotics were used for adults patient with FUO eventhough they are not recommended.  Agreement among the prescribers is urgently needed to standardize the management of FUO in Panti Rapih Hospital.  Effort should be sought to update the improving standard diagnosis and treatment guideline for FUO.