Drug Utilization and Evaluation of Cephalosporin s At Tertiary Care Teaching Hospital, Bangalore

Transcription

1 Research Article Drug Utilization and Evaluation of Cephalosporin s At Tertiary Care Teaching Hospital, Bangalore HS. Shekar 1*, HR. Chandrashekhar 2, M. Govindaraju 3, P. Venugopalreddy 1, Chikkalingiah 2 and Anil 4 1 Department of Pharmacy Practice, KIMS Hospital and Research Centre, Bangalore, Karnataka, India. 2 Department of General Medicine, KIMS Hospital and Research Centre, Bangalore, Karnataka, India. 3 Department of Molecular Bio-Physics, Indian Institute of Science (IISC), Bangalore, Karnataka, India. 4 Department of ENT, KIMS Hospital and Research Centre, Bangalore, Karnataka, India. ABSTRACT Drug therapy is considered to be major component of patient management in health care settings, including primary healthcare. Although the benefits patients gain from pharmacological interventions are valuable the risks of drugs per se and consequences of inappropriate use cannot be overlooked. Of the various classes of drugs, antibiotics receive special attention as more money is spent on them than any other class of drugs. Some antibiotics also have specific side effects and extensive antibiotics use can lead to the development of resistance to drugs. Among all antibiotics, cephalosporins are the largest and most diverse family of antibiotics available. cephalosporins due to their extended spectrum of activity are widely used in hospital setups. The spiraling cost of these drugs and chances of developing resistance due to their wide spread use has warranted the need for drug utilization evaluation (DUE) of this class of antibiotics. DUE is a tool for monitoring the appropriateness of prescribing patterns and utilization of drugs. Therefore the present study was aimed to evaluate the appropriateness of use of cephalosporins in terms of choice of drug, dose, frequency of administration, route of administration, duration of therapy, drug interactions and development of adverse drug reactions. A concurrent treatment chart review of patients admitted to the medicine department was done for a period of 6 months. Totally 300 patients prescribed with cephalosporins were included for the study. Cephalosporins utilization data was collected from the first 150 patients. Later guidelines regarding the use of cephalosporins was developed in coordination with the respective clinicians and their approval for the guidelines was sought. Copy of the guidelines for the use of cephalosporins was distributed to all the clinicians including postgraduates, interns and nurses and they were requested to incorporate the message in the guidelines in their regular clinical practice. Further cephalosporins utilization data was collected from another 150 patients after the implementation of guidelines. Results revealed that the overall appropriateness of use of cephalosporins before the implementation of the guidelines was 76% for choice of drug, 68% for dose, 77.33% for frequency of administration, 82.67% for duration of therapy, 100% for route of administration, 64% for drug interactions and 97.33% for ADRs before the implementation of the guidelines. The overall appropriateness of use of cephalosporins after the implementation of the guidelines was for choice of drug, 96% for dose, and 98.67% for frequency of administration, 96% for duration of therapy, 100% for route of administration, 92.67% for drug interactions and 98.67% for ADRs after the implementation of the guidelines. The overall increase in appropriateness of cephalosporins were found to be 15.33% of choice of drug, 28% of dose, 21.34% of frequency of administration, 13.33% of duration of therapy and 28.67% of drug interactions. Chi square test was used to assess the impact of guidelines on the utilization of cephalosporins. Guidelines significantly (P<0.05) improved the utilization of cephalosporins with respect to all the parameters. Keywords: Drug Use Evaluation, Drug Use Review, Rational Use of Drugs, Adverse Drug Reactions. Vol. 4 (4) Oct Dec

2 INTRODUCTION Drug therapy is considered to be major component of patient management in healthcare settings, including primary healthcare. Although the benefit patient s gain from pharmacological interventions are valuable, the risks of drugs per se and consequences of inappropriate use cannot be overlooked. 1 The introduction of potent drugs with an increased incidence of adverse drug reactions, the high cost of medication, and a focus on drug use outcomes and the clinical misuse of drugs may result in preventable patient morbidity and mortality, costly remedial care, additional cost for diagnosis and management of iatrogenic disease and unnecessary wastage of health resources. Inadequate knowledge of treatment regimens, lack of diagnostic competence have contributed to incorrect drug choices, incorrect dose, adverse drug reactions, drug interactions, and use of more expensive drugs when less expensive drugs would be equally or more effective. 2 In recognition to this problem, DUE (drug utilization and evaluation) has been recommended as a method for identifying inappropriate or unnecessary drug use that monitor, evaluate and promote rational drug therapy. 3,4,5 Several factors like irrational drug use, polypharmacy, incorrect drug choices, incorrect dose, drug interactions, have contributed to increased morbidity, mortality and health care expenses or use of drugs devoid of proven efficacy. 6,7 The misuse or inappropriate use of this group of antibiotics leads to increase in healthcare expenses, development of drug resistance and serious adverse drug reactions. 8 Hence in this study we aimed to carryout DUE of cephalosporins in medicine department of Victoria Hospital (a tertiary care govt. hospital) located at Bangalore in order to evaluate their use, educate the clinicians by providing guidelines and evaluate the impact of providing guidelines on the use of cephalosporins and to promote the quality use of cephalosporins. Objectives: To determine the extent, appropriateness use of cephalosporins with respect to dose, duration, frequency of administration and cost. We also aimed to identify the infections for which cephalosporins are given and to assess the appropriateness of use of cephalosporins for the respective infections. were included for the study. All out patients treated with cephalosporins, all inpatients from all other departments, other than medical department treated with cephalosporins were excluded from the study. A total of 300 patients who met the inclusion criteria were selected for the study. Informed consent was obtained from those patients who were included for the study. The data for the study was collected from the case notes, prescriptions, laboratory reports and treatment charts of the patients. Cephalosporins utilization data was collected from the first 150 patients prior to the development of guidelines. Later guidelines regarding the use of cephalosporins was developed after reviewing relevant literatures, electronic database, microbiological culture sensitivity data (annexure) and standard textbooks with respect to indication, criteria, threshold in coordination. Draft guidelines were shown to Physicians for their suggestions and approval. Copies of the guidelines for the use of cephalosporins were distributed to all the clinicians including postgraduates, interns and nurses with a request to incorporate the information in the guidelines in their regular clinical practice. Drug utilization data was again collected from another 150 patients who were put on cephalosporins after development and distribution of guidelines to clinicians. RESULTS The study results showed that the most prescribed cephalosporins were ceftriaxone, cefatoxime, cefexime, cefepime and ceftazidime. The most common infections were Enteric fever, pneumonia, AECB, meningitis, UTI, URTI, Septicemia, Skin and STD, Bone and Joint, Endocarditis. Out of 5 cephalosporins which are commonly prescribed by the clinicians of Victoria Hospital, only ceftriaxone and cefotaxime was available in the hospital during the study period. Drug utilization guidelines increased the appropriateness of use of cephalosporins with respect to all the parameters. Maximum improvement was observed with respect to dose (26.67%), followed by avoiding drug interaction (26.66%), frequency of administration (26%), duration of therapy (13.33%) and choice of drug (12%). MEHTODS The study was conducted for a period of 6 months in the medicine department of Victoria Hospital, Bangalore, a 968-bed tertiary care teaching hospital attached to Bangalore Medical College. Ethical committee clearance was obtained from ethical committee, Bangalore Medical College and permission from Medical superintendent of the hospital was obtained prior to the study. All the inpatients of medicine department treated with cephalosporins at Victoria Hospital, Bangalore Vol. 4 (4) Oct Dec

3 Table 1: Appropriateness of use of Cephalosporins before implementation Drugs Choice of drug Dose Frequency Duration Route of Drug administration interactions ADRs No. % No. % No. % No. % No. % No. % No. % Ceftriaxone 48/ / / / / / / Cefotaxime 39/ / / / / / / Cefixime 12/ / / / / / / Cefepime 8/ / / / / / / Ceftazidime 7/ / / / / / / Table 2: Appropriateness of use of Cephalosporins after implementation of the guidelines Choice of drug Dose Frequency Duration Route of ADM Drug Interactions ADRs Drugs No. % No. % No. % No. % No. % No. % No. % Ceftriaxone 75/ / / / / / / Cefotaxime 35/ / / / / / / Cefixime 9/ \ \ \ \ \ \ Cefepime 12/ \ \ \ \ \ \ Ceftazidime 6/ \ \ \ \ \ \ Comparison of utilization of each cephalosporin with respect to the set parameters before and after the implementation of guidelines using chi square test reveled significant improvement in the utilization of cephalosporins. Parameters Table 3: Appropriateness of use of Ceftriaxone Before Implementation in % (N=69) After Implementation in %(N=85) Choice of drug Dose < Frequency Duration Route of administration Drug Interactions < ADRs P DISCUSSION Comparison of appropriateness of use of ceftriaxone before and after the implementation of guidelines in order to evaluate the impact of guidelines on the utilization of ceftriaxone using chi square test revealed that guidelines have produced significant (P<0.001) improvement in the utilization of ceftriaxone. Improvement was observed with respect to all the parameters except route of administration and development of adverse drug reactions. Comparison of choice of use of ceftriaxone before the implementation of guidelines revealed that the use of ceftriaxone was found to be inappropriate in 21 cases. Out of these 21 cases there were 2 cases of bacterial meningitis where in amoxicillin, clavulunate potassium would have been better choice of drug, and in 2 cases of N. meningitis benzyl penicillin would have been better choice, and in 2 cases of UTI amoxicillin/ampicillin would have been better choice of drug. In 15 cases of enteric fever ciprofloxacin would have been better choice of drug. Appropriateness of choice of drug improved after the implementation of guidelines. Ceftriaxone was inappropriately used only in 10 cases after the implementation of guidelines when compared to 21 cases before the implementation of guidelines of which there were 6 cases of community acquired pneumonia wherein clarithromycin/azithromycin/doxicyclin would have been better choice of drug. In 4 cases of enteric fever ciproflaxacin would have been better choice. Comparison of appropriateness of dose before and after implementation of guidelines revealed that dose of ceftriaxone was inappropriate in 23 cases of which there were 12 cases of pneumonia where in ceftriaxone was used at the dose of 1gm/day but 2gm IV 12 th hourly is the recommended dose. In 8 cases of enteric fever ceftriaxone was used at 1gm/day but the recommended dose is 4 gm/day. In 1 case of meningitis ceftriaxone was used at the dose of 1 gm/day but the recommended dose is 2gm 12 hourly. In 2 cases of uncomplicated UTI with renal Vol. 4 (4) Oct Dec

4 failure the given dose was 1gm/day but the recommended dose is 2 gm/day. After the implementation of guidelines the dose of ceftriaxone was inappropriate in only 4 cases as against 21 cases before the implementation of guidelines. Out of these 4 cases 2 cases were pneumonia and another 2 cases were enteric fever. In pneumonia ceftriaxone was used at the dose of 1gm/day but the recommended dose was 2gm IV 12 hourly. In enteric fever ceftriaxone was used at the dose of 12gm/day but the recommended dose is 4gm/day. Comparison of appropriateness of dose using chi square test revealed a significant improvement (P<0.001). The appropriate use of ceftriaxone dose improved significantly (P<0.001) after the implementation of the guidelines and the improvement was found to be 28.59%. The inappropriateness in frequency of administration was found in 15 cases before the implementation of guidelines of which in 3 cases of septicemia 1gm/day was given but the guideline recommends dose was 1gm BID. In 12 cases of pneumonia 1gm/day has given but the recommended dose is 2gm 12 hourly. In post implementation phase inappropriateness of frequency of administration of ceftriaxone has occurred in 1 case of endocarditis 2gm thrice a day has been given but the guidelines recommends is 1-2 gm BID, in 2 cases of pneumonia 1gm once has been given but the guidelines recommends 2gm 12 th hourly. The appropriateness of frequency of administration of ceftriaxone increased After the implementation of guidelines was 24.29% and the P value is is statistically extremely significant. The appropriateness of use of duration of therapy of ceftriaxone was increased after the implementations of the guidelines and were found to be 17.58% & the P value is considered statistically extremely significant. Inappropriateness in the duration of ceftriaxone use was observed in 17 cases of which 10 cases were gets discharged (6 cases of enteric fever and 4 cases of pneumonia) used 3-4 days and in 3 cases of Enteric fever was given for 13 days. 4 cases of meningitis were the guidelines recommended days of treatment but they were treated only for 5 days. In post implementation phase there are 6 cases of inappropriate duration of ceftriaxone of which 5 cases of enteric fever were used 3 days of ceftriaxone therapy and 1 case of pneumonia got discharged. The route of administration of ceftriaxone was appropriate in both pre and post implementation phase found to be 100%. In pre implementation phase 34 cases of ceftriaxone were found to have drug interaction out of which 17 cases with furosemide, 11 cases with diclofenac potassium and 6 cases with amikacin. In the post implementation phase also there were 7 cases of drug interaction with furosemide. In 3 cases pain occurs at the site of injection and vomiting in one case before implementation of the guidelines & in post implementation phase also occurs pain at the site of injection in 2 cases. Comparison of impact of cefotaxime usage guidelines before and after the implementation of guidelines using chi square test revealed significant improvement in the utilization of cefotaxime with respect to many parameters. The choice of cefotaxime before the implementation of guidelines was inappropriate in 15 cases of which 9 were of community acquired pneumonia where in oral therapy of clarithromycin/azithromycin/doxicyclin would have been the better choice of drug. There were 3 cases of enteric fever where in ciprofloxacin/amoxicillin would have been better choice of drug and ampicilin or gentamycin would have been a better choice in the remaining 3 cases (uncomplicated UTI) where ceftriaxone was used inappropriately. In post implementation phase ceftriaxone was used inappropriately in 3 cases of community acquired pneumonia clarithromycin or azithromycin or doxicyclin would be the better choice of drug. The route of administration of ceftriaxone was appropriate in all the patients both before the implementation of guidelines and none of the patients put on ceftriaxone developed any adverse drug reactions to it. Comparison of dose of cefotaxime utilized before the implementation of guidelines revealed that the dose was inappropriate in 13 cases of which there were 4 cases of meningitis where in cefotaxime was given at the dose of 0.5 gm/day, but the recommended dose is 2gm 6 th hourly. Similarly dose of cefotaxime was inappropriate in 3 cases of UTI where in cefotaxime was given at 2gm/day but the recommended dose is 0.5gm IV 8 th hourly. The dose was inappropriate even in the treatment of pneumonia and AECB (each 3 cases) wherein cefotaxime was given at 1gm/day but the recommended dose is 2gm IV 12 th hourly. In post implementation phase the inappropriateness of dose of cefotaxime occurred only in 4 cases of which under dosing occurred in 3 cases of meningitis and over dosing occurred in 1 case of UTI. Significant (P<0.01) improvement in the utilization of cefotaxime was observed after the implementation of guidelines with respect to all the parameters except route of administration, drug interactions in the prescriptions and adverse drug reactions developed. The increase in appropriateness of frequency of administration of cefotaxime was found to be 24.08% after the implementation of the guidelines and the P value is is statistically extremely significant. In preimplementation phase in 13 cases the frequency of cefotaxime administration was inappropriate of which 4 cases, the recommended dose was 2gm 6 th hourly but prescribed 1gm O.D, in 3cases of pneumonia, 3 Vol. 4 (4) Oct Dec

5 cases of UTI, 1 case of Skin & STD, 1 case of bone and joint infections used 1gm O.D. dose but the guidelines recommends 1gm IV 6-12 th hourly and 1 case of septicemia 1gm O.D dose has been given but the recommended dose is 1gm IV 8 th hourly. The increase in appropriateness of duration of therapy of cefotaxime were found to be 16.67% and the P value is is statistically extremely significant. In the pre implementation phase the 9 cases of duration of therapy were found to be inappropriate of which 6 cases of meningitis the treatment was given for only 6 days but the guidelines recommends days, in 3 cases of UTI the treatment was given only for 5 days but the guidelines recommends 14 days. In post implementation phase the duration of therapy of cefotaxime was appropriate. The routes of administration of cefotaxime were found to be appropriate in both pre and post implementation phase. In pre implementation phase 11 cases were found to have drug interaction with cefotaxime of which 7 cases with amikacin and 5 cases with gentamycin. In post implementation phase 1 case found to have drug interaction with the amikacin. The adverse drug reactions are not occurred in pre and post implementation phase due to cefotaxime. Similar to ceftriaxone the route of administration of cefotaxime was found to be appropriate in all the patients both before and after the implementation of guidelines. The increase in the appropriateness for the parameter like choice of drug of cefotaxime is found to be 19.88% after the implementation of the guidelines and the P value is statistically significant. Few drug interactions were observed in the prescriptions containing cefotaxime both before and after the implementation of guidelines and the significance of the difference was found to be P<0.05. None of the patients developed any adverse drug reactions to cefotaxime. Analysis of utilization of cefixime using chi square test revealed significant (P<0.05) difference. While utilization of cefixime with respect to duration of therapy and route of administration was found to be appropriate in all the patients both before and after the implementation of guidelines. The appropriateness of choice of cefixime was appropriate in pre and post implementation phase. The dose of cefixime was inappropriate in 6 cases out of which in 5 cases of AECB as well as in UTI 100mg B.I.D have been given but the indicated dose is 400mg/day. In the post implementation phase the dose of cefixime was appropriate in all the cases. The increase in appropriateness of frequency of administration of cefixime was found to be 50% after the implementation of the guidelines. In preimplementation phase, in 6 cases the frequency of administration of cefixime was inappropriate, of which 5 cases of AECB the guidelines recommends O.D. but used B.I.D. and in 1 case of uncomplicated gonorrhea the indicated frequency is 400mg O.D. but used 100mg B.I.D. in the pre implementation phase the frequency of administration of cefixime was appropriate. The duration of therapy and route of administration of cefixime was appropriate in both pre and post implementation phase. In the preimplementation phase cefixime was found to have interaction with 7 cases prescribed with amikacin. In post implementation also interaction occurs with amikacin but occurs in 2 cases. There are no ADRs of cefixime occur in both pre and post implementation of the therapy. The incidence of adverse drug reactions due to cefixime was found to be zero % both before and after the implementation of guidelines. Cefepime was appropriately used with respect to all the parameters in all the patients both before and after the implementation of guidelines when compared to all other cephalosporins and therefore the chi square evaluation did not yield significance. In preimplementation phase cefepime were found to have interaction with 4 cases of furosemide and it reduced to 1 case with the same drug after implementation of guidelines. Guidelines have produced significant (P<0.001) improvement in the utilization of ceftazidime with respect only one parameter i.e. dose. The use of ceftazidime was appropriate in both pre and post implementation phase for the parameters like choice of drug, frequency of administration, duration of therapy, route of administration, drug interactions and ADRs. In pre implementation phase the dose of the ceftazidime was inappropriate in 6 cases of which 3 cases of septicemia, 2 cases of URTI and in 1 case of enteric fever 500 mg/day but the guidelines recommends 1-6 gm/day. In post implementation phase the dose of ceftazidime was found to be appropriate. While utilization of ceftazidime with respect to all the other parameters was found to be appropriate as per the guidelines both before and after the implementation of guidelines. Comparison of overall appropriateness of use of cephalosporins for the set of parameters revealed that significant improvement (P<0.001) was observed with respect to all drugs and all parameters except route of administration and adverse drug reactions. The appropriateness of use of cephalosporins in various infections for the various parameters before the implementation of guidelines for the parameters, choice of drug, dose, frequency of administration, duration of therapy, route of administration, drug interactions and adverse drug reactions were account to be 76%, 68%, 77.33%, 82.67%, 100%, 62.67%, 97.33% respectively. The appropriateness of use of cephalosporins in various infections for the various parameters after Vol. 4 (4) Oct Dec

6 the implementation of the guidelines accounts for, choice of drug, dose, frequency of administration, duration of therapy, route of administration, drug interactions and adverse drug reactions were, 91.33%, 96.67%, 98.67%, 96%, 100%, 92.67%, 98.67% respectively. The study shows overall increase in appropriateness of use of cephalosporins in medicine departments with respect to choice of drug 15.33%, dose 28.0%, frequency 21.34% duration of therapy 13.33%, drug interactions 30.00% and adverse drug reactions 1.34%. In conclusion this drug utilization evaluation study improved the use of cephalosporins in the medicine department of Victoria Hospital, Bangalore. Results showed marked decrease in inappropriate use of cephalosporins and increased their appropriate use. The prepared guidelines for the use of cephalosporins had a positive impact in the clinical practice and was well accepted by the practitioners and proved to be useful in their clinical practice. 11. REFERENCES 1. Food and Drugs Act. ( 2. Munir Pirmohamed, Alasdair M Breckenridge, Neil R Kitteringham and Kevin Park B. Adverse Drug Reactions, BMJ. 1998; 316: Palaian S, Mishra P, Shankar PR, Dubey AK, Bista D and Almeida R. Safety monitoring of drugs - Where do we stand? Kathmandu University Medical Journal, 2006;4(1): World Health Organization. International monitoring of adverse reactions to drugs: adverse reaction terminology. Uppsala: WHO Collaborating Center for International Drug Monitoring, Karch FE and Lasagna L. Adverse drug reaction - A critical review. JAMA. 1975; 234: Classen DC, Pestotnik SL, Evans RS, Lloyd JF and Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1997;277: Smith DL. The effect of patient noncompliance on healthcare costs. Medication Interface.1993;6(4):74-6,78, Faich GA. Adverse-drug-reaction monitoring. N Engl J Med. 1986; 314: Vol. 4 (4) Oct Dec