Title: Investigation of antimicrobial use pattern in the intensive treatment unit of a teaching hospital in western Nepal

Names of authors:

Dr.P.Ravi Shankar MD

Dr. Praveen Partha DNB

Mr. Nagesh Shenoy MPharm

Dr.K.N.Brahmadathan PhD

Names of the departments in which the work was carried out:

Departments of Internal medicine, Clinical pharmacology and Microbiology, Manipal teaching hospital, Pokhara, Nepal.

Name and address of corresponding author:

Dr.P.Ravi Shankar

Department of Pharmacology

Manipal College of Medical Sciences

P.O. Box 155

Deep Heights

Pokhara, Nepal.

Fax:00977-61-22160.

E-mail: mcoms@mos.com.np

pathiyilravi@rediffmail.com

Title: Investigation of antimicrobial use pattern in the intensive treatment unit of a teaching hospital in western Nepal

Abstract:

Introduction: Inappropriate use of antimicrobials is of special importance in the intensive treatment unit because of the large number of drugs prescribed, the chance for drug errors and the likelihood of development of drug resistance. Methods: 297 inpatient records of patients admitted to the intensive treatment unit of the Manipal teaching hospital, a tertiary care hospital in Pokhara, western Nepal were studied to determine the prescribing frequency and rationality of use of antimicrobials. The patient outcome, the duration of stay in the intensive care unit and the age and sex distribution of the patients were also studied. Results: Mean ± SD drugs per patient was 3.45 ± 1.78. 50.17% of the patients received an antimicrobial. 84.56% of the antimicrobials were used without obtaining bacteriological evidence of infection. The commonest organisms isolated on culture were Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. 28.86% of the antimicrobials were prescribed for lower respiratory tract infections based on the putative site of infection. 61.86% of the antimicrobials were prescribed by the parenteral route and mainly the older generation of antimicrobials were used. In 39 out of the 149 patients prescribed an antimicrobial the use was irrational. Conclusions: Prescriber education to improve prescribing patterns and regular auditing of antimicrobial prescriptions to prevent their irrational use as well as unnecessary cost to the patients are required. The high percentage of irrational use of antimicrobials raises concerns about the development and spread of drug resistance and this has to be addressed.

Drug utilization review (DUR) is the process by which the quality of drug prescribing is measured by organizing important predetermined criteria.¹ In the developing countries the cost of drugs is a major concern to both physician and patient.² Analysis of indication-related drug prescription patterns is of particular interest with regard to rising costs of the health service.³ This is also reflected in the higher costs of drugs, especially antibiotics. Widespread concern has been expressed about the inappropriate use of antimicrobials.⁴ This is especially true of the intensive treatment unit (ITU) as errors in prescription, administration, delivery and interaction of drugs are likely because of the large number of medications prescribed.⁵ Also inappropriate and irrational use of antimicrobials can lead to microbial resistance to the commonly used antimicrobials. This in turn can lead to the use of costlier, newer antibiotics to combat the problem of microbial resistance. This is an issue of great concern to a developing country like Nepal.

Medical audit oversees the observance of standards of medical treatment at all levels of the health care delivery system.⁶ It is also defined as the evaluation of medical care in retrospect through analysis of clinical records. The study of prescribing patterns is a component of medical audit which seeks monitoring, evaluation and necessary modification in the prescribing patterns of prescribers to achieve rational and cost effective medical care.⁷

Review of the antimicrobial use pattern in the ITU, knowledge about the different strains of micro-organisms and their sensitivity patterns are useful in formulating infection control strategies in the ITU. Development of resistant organisms due to inappropriate use of antimicrobials can lead to the spread of these organisms in the wards as patients are often shifted to the wards once they get better. So prevention of inappropriate antimicrobial use is important for infection control strategies in our hospital.

We report here the results of a retrospective analysis of the pattern of antimicrobial drug use over a one year period (15.06.2000 to 15.06.2001) in the intensive treatment unit of a teaching hospital in western Nepal.

Materials and methods:

All the inpatient records of patients admitted to the ITU during the time period noted in the study were taken for analysis. All the relevant details from each inpatient record were entered into a proforma for analysis. The following details were entered: age, sex, address, diagnosis, outcome, duration of stay in the ITU, details of a culture and sensitivity test if done (patient details); antimicrobials prescribed, quantity, dosage form and route, duration and cost (drug details). Whether the antimicrobials used were prescribed from the Essential drug list of Nepal⁸ or not was noted. Further whether the use of the antimicrobial was indicated for the condition and whether generic or brand name of the drug was used was also noted. The study was approved by the institutional review board of the Manipal teaching hospital, Pokhara.

An infection was suspected by the doctors on the basis of clinical signs and symptoms. Fever, coughing out of purulent sputum, dysuria and other clinical features along with the investigations were helpful in arriving at a diagnosis. Empiric treatment with antimicrobials was started after taking appropriate samples for culture and sensitivity. The treatment may be modified later in the light of the culture reports.

The purpose of the study was to determine whether the drug prescribing was based on rational therapeutic considerations with reference to the particular diagnosis and the possibility of development of drug resistance.

Results and Conclusions:

Critical care services are an identified, resource-intensive component of the health care services. Examining cost containment and clinical effectiveness in this specialty is therefore highly appropriate, although difficult to achieve in practice. The high prevalence of infections in critically ill ITU patients is associated with high antimicrobial consumption. Besides the economic impact of the high cost associated with antimicrobial treatment in the ITU there is the constant threat of selection and induction of antimicrobial resistance.

297 inpatient records of patients admitted to the ITU were audited. 183 male patients (61.6%) and 114 female patients were admitted to the ITU during the study period. 195 patients (65.6%) were discharged from the ITU, 65 (21.9%) died during the period of hospitalization in the ITU, 17 (5.7%) were referred to other centers and 10 patients (3.4%) left against medical advice.

The age distribution of the patients admitted to the ITU is shown in Table 1. 159 of the 297 patients (54.6%) were above 55 years. The average age of the patients admitted to the ITU was 53.9 ± 19.9 years. 50 patients (16.8%) were admitted to the ITU for a day, 197 patients (66.3%) for a time period between 2-5 days, 39 patients for a period ranging from 6 to 10 days and 11 patients for a time period greater than 10 days. The average period for which a patient was admitted in the ITU was 3.8 ± 3.2 days. Economic constraints were a major reason for the patients and their families requesting an early discharge from the ITU.

The majority of the patients (57.9%) admitted to the ITU hailed from Pokhara city and the district of Kaski of which Pokhara is the headquarters. Another 76 patients (25.6%) were from the neighboring districts of Syangja and Tanahun. Majority of the patients came from within a radius of 75 km.

149 patients (50.2%) admitted to the ITU received one or more antimicrobials. In previous studies the prevalence of antimicrobial use in the ITU was around 61%.^9,10However the antimicrobial use was supported by bacteriological evidence in only 37 patients (24.8%). In a previous study⁹ only 41% of the antimicrobials were used without bacteriological support. Rational prescribing can only be expected if the prescriber is aware of the most likely infecting agent.¹¹ The prescribing frequency of combination antimicrobials in our study was 14.6%. 84.4% of the combination prescriptions were for the combination of ampicillin and cloxacillin.

The most common indication for antimicrobial use was acute exacerbation of chronic obstructive pulmonary disease (COPD) (n=23). The other common reasons were: pneumonia (n=20), head injury (n=9), hepatic encephalopathy (n=9) and surgical prophylaxis (n=7).

70.5% of the patients (n=209) who received an antimicrobial during their stay in the ITU were medical patients while 29.5% were surgical patients. Antimicrobials were used for prophylaxis in 46 patients (30.9%), for non-bacteriologically proven infection (non-BPI) in 76 patients (51 %) and for bacteriologically proven infection (BPI) in 27 patients (18.1%). The antimicrobials were used for prophylaxis for a period less than 3 days in 8 cases (17.4%), for a time period between 3-5 days in 9 cases (19.6%), for a time period between 5-7 days in 15 cases (32.6%) and for a time period equal to or greater than 7 days in 14 cases (30.4%). In previous studies ^10,12 antimicrobials were used for prophylaxis in 13% and 10.3% of patients respectively.

Prophylactic usage of antimicrobials showed metronidazole, ampiclox, gentamicin, ampicillin and cefotaxime to be the most frequently prescribed in that order. Since this is one area of antimicrobial usage which is easily abused and the consequences can be costly and dangerous, it calls for a continuous audit and review. The use of ampiclox for surgical prophylaxis is a matter of concern and has to be looked into.

In those patients admitted to the ITU and who received an antibiotic the cost of the antibiotic treatment during the period of hospitalization in the ITU was 818 ± 320.3 Nepalese rupees (11.2 ± 4.3 US dollars).

The commonest specimen sent for the culture and sensitivity tests was sputum (n=12) followed by urine (n=11). The commonest organisms isolated were P.aeruginosa (n=4), K.pneumoniae (n=4) followed by S.pneumoniae (n=3) and S.aureus (n=3). The cultures were negative in 12 cases.

Use of individual antimicrobial agents forms the most important index of ongoing antimicrobial audit programs as it indicates the changes in pattern of usage and in susceptibility patterns of bacteria and also gives information regarding the introduction of newer antimicrobials. The frequency of prescribing of the 10 most commonly prescribed antimicrobials in the ITU is shown in Table 2. The most commonly prescribed antimicrobials were metronidazole (n=56), ampicillin (n=46), combination of ampicillin and cloxacillin (n=41) and gentamicin (n=36). The prescription of cephalosporins were less than that reported in previous studies¹¹ and vancomycin was not prescribed in the ITU. The prescription of aminoglycosides three times daily was 25% and the prescription frequency of once daily gentamicin was 37%. The combination preparation co-amoxiclav was very costly. The cost of the drugs prescribed is an important consideration especially in a poor, developing country like Nepal.

In 39 out of the 149 cases (26.2%) the use of the antimicrobial was irrational on retrospective analysis of the case record. Common examples of irrational prescribing were prescription of a third generation cephalosporin where a cheaper antimicrobial would have been satisfactory, use of a cocktail of antimicrobials with overlapping spectrums for abdominal infections, use of antimicrobials in cases of cerebrovascular accidents and acute confusional states. Costly antimicrobial combinations and newer antimicrobials were used where an older antimicrobial would have worked satisfactorily.

Moss et al.¹³ found that most of the prescribers in their study based therapy only on the anatomical site of the putative infection and lower respiratory tract was the most frequently targeted site. This also holds true for this study were 28.9% of the antibiotics prescribed were for lower respiratory tract infections.

The route of administration of an antimicrobial is influenced by the site and severity of infection as well as the cost of treatment. In an ITU with critically ill patients the use of parenteral antimicrobials is expected to be high. In our study 61.9% of the antimicrobials were prescribed by the parenteral route.

Most of the organisms isolated from the ITU were sensitive to the commonly used antimicrobials ampicillin, gentamicin, cefotaxime and ciprofloxacin. This is in contrast to reports in other studies^14,15 where the organisms were resistant to cephalosporins, broad-spectrum penicillins and to ciprofloxacin. However, the low number of cultures carried out in our study makes it difficult to draw any firm conclusions.

At the present time we do not have a pre-existing antibiotic policy in our hospital. The individual departments and the intensive care unit are in the process of framing antimicrobial use guidelines. The common organisms causing infections in the ITU and their antimicrobial sensitivity patterns were studied. Due to economic considerations and sensitivity tests could not be done for a number of patients. We plan to use the findings to develop an antibiotic use policy for the ITU. Similar studies are being planned in the different wards and these data will be used to develop a hospital antimicrobial policy which will be an important element of infection control.

The study findings call for a review of antimicrobial drug utilization patterns in the ITU in so far as the large number of drugs prescribed (n=31), lack of bacteriological confirmation of infections in the majority of patients and inappropriate and irrational prescribing. However, it is difficult to make more specific recommendations as the choice of the antimicrobial is dependent on multiple factors, not all of which are under the control of the prescriber.

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* a person may be receiving more than one antimicrobial