pharmacoepidemiology and drug safety 2004; 13: 653–657Published online 6 January 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pds.927

ORIGINAL REPORT

Utilization of parenteral anti-infective agents in the medicalemergency unit of a tertiary care hospital: an observationalstudy{

M. Gupta1, S. Malhotra1, K. K. Chandra1, N. Sharma2 and P. Pandhi1*

1Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh, India2Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India

SUMMARY

A pharmacy based prescription audit was undertaken in the medical emergency unit of a tertiary care hospital to determinethe frequency of prescribing of parenteral anti-infective agents. During the study period, 885 patients were screened. Theanalysis was done for the number of parenteral anti-microbials in each prescription frequency of individual drug prescribenumber and dose unit (DDD), frequency of age and sex, site of infection and daily cost incurred by the patient. It was foundthat 400 patients (45.2%) received parenteral anti-infective agents. Cephalosporins, aminoglycosides and metronidazoleaccounted for about 70% of total antimicrobial use. More than 50% of patients had culture sensitivity reports available.The mean (standard deviation, SD) daily cost of antibiotic was US $ 3.8 (7.7), median; range 2 (0.1–85.7). Two anti-microbials per prescription were indicated in most of the patients (43.88). In conclusion we have provided an overviewof parenteral anti-infective use in medical emergency, which may serve as a basis for intervention and improvement inprescribing pattern of parenteral anti-microbials. Copyright # 2004 John Wiley & Sons, Ltd.

key words— medical audit; prescription; drug utilization

INTRODUCTION

Drug utilization studies serve as a tool of investigationfor clinical pharmacology as well as a source of sug-gestive information for epidemiology. Drug utilizationhas been defined by the WHO as the marketing, distri-bution, prescription and use of drugs in a society with aspecial emphasis on the resulting medical, social andeconomic consequences.1 Auditing of prescriptionsalso forms part of drug utilization studies.2 The studyof prescribing patterns is a component of medicalaudit, which seeks monitoring, evaluation and neces-sary modifications in the prescribing practices toachieve rational and cost effective medical care.

The important therapeutic role played by anti-microbials coupled with the ongoing threat of bacterialresistance are compelling reasons for concern aboutadequate and appropriate use of these agents. Further-more, anti-infective agents are responsible for a largeproportion of the costs of the health care system indeveloping countries. Also, studies regarding theutilization of anti-microbials in emergency are fewand there is recent evidence of inappropriate use in upto 50% of patients with community acquired pneumo-nia in an emergency department setting.3

A preliminary pilot study on the use of anti-microbials in the medical emergency unit of ourhospital showed that 76.2% of those receiving anti-infective agents receive only parenteral therapy. Afurther 21.6% received both oral and parenteraltherapy. In view of above finding, the utilization ofparenteral anti-infective agents in patients visitingemergency unit was evaluated in the present study.

Received 22 July 2003Revised 23 October 2003

Copyright # 2004 John Wiley & Sons, Ltd. Accepted 4 November 2003

* Correspondence to: Dr P. Pandhi, Department of Pharmacology,PGIMER, Chandigarh-160012, India.E-mail: samirmalhotra345@yahoo.com{No conflict of interest was declared.

PATIENTS/METHODS

The study was carried out for a period of 6 months(January 2002–June 2002) in the medical emergencyunit of the Nehru Hospital, Post Graduate InstituteMedical Education and Research, Chandigarh, Indiaby evaluating the inpatient treatment charts. The datacollection was done using a predesigned proformawhich included patient’s age, sex, diagnosis, the siteof infection for which the parenteral antibiotic wasgiven and the name of the drug, number of its dosageunits, whether prescribed in generic name or not. Dataanalysis was done in terms of the number of anti-infective agents in each prescription, the frequencyof individual drug used, age and sex of the patient,the site of infection and daily cost. The drugs werefurther classified according to the ATC system (Ana-tomical Therapeutic Chemical Classification.4 Thedrug prescribing prevalence was expressed as defineddaily dose (DDD)/100 bed days.1

RESULTS

Of the 885 patients screened, 400 patients (45.2%)received parenteral anti-infective agents. The predo-minant respiratory etiology for parenteral anti-infectives include community acquired pneumoniafor prophylaxis and treatment of aspiration pneumo-nia in patients with cerbrovascular accident (CVA)and diabetic ketoacidosis (DKA). All regimens forpneumonia of either kind had a �-lactam antibiotic

and metronidazole in 25% of patients. Amikacinwas added to these regimens mostly when the etiologywas aspiration pneumonia. For acute exacerbation ofCOPD a �-lactam (in 75%) or a quinolone (37.5%) orboth were used with amikacin in approximately halfof these receiving �-lactam antibiotics. Meningitisor encephalitis (or undiagnosed encephalopathy)was the main cause of CNS injections requiringanti-infectives. All these patients received �-lactamantibiotics either alone or along with amikacin(32%) or metronidazole, with few patients receivinganti-fungal (amphotericin-B) and anti-viral (acyclo-vir) agents also. For liver and bile duct related infec-tions patients received a �-lactam alone (60%) or withamikacin and/or metronidazole. Majority of acutepancreatitis patients received a quinolone (78%) alone.

Overall, 29 different parenteral anti-infective agentswere used. Cephalosporins, aminoglycosides andmetronidazole accounted for about 70% of total anti-microbial use. The use of more than one anti-microbialagent among the 400 patients was also evaluated. Twoanti-microbials per prescription were indicated in43.88% of patients, single anti-microbial treatmentwas found in 33.55%, three drugs in 22.5% and fourdrugs in 3%. Approximately 43% of the drugs wereprescribed by their trade names. More than 50% ofpatients had culture sensitivity reports available. Therewas no significant difference in prescribing frequencyof any anti-infective agent in males and females(Tables 1 and 2). The most frequently prescribed

Table 1. Age-wise prescribing frequency of parenteral anti-infective agents in males

Age group Total no. ofpatients

Penicillinþcephalosporins

Quinolones Aminoglyco-sides

Antiprotozoal Glycopeptides Others Total no. ofprescriptions

11–20 21 16 (43.2) 05 (13.5) 06 (16.2) 07 (18.9) 01 (2.7) 02 (5.4) 37 (100)21–30 49 39 (39) 13 (13) 24 (24) 17 (17) 02 (02) 05 (05) 100 (100)31–40 39 30 (39.5) 11 (14.5) 12 (15.8) 20 (26.3) 02 (2.6) 01 (1.3) 76 (100)41-50 49 42 (43.8) 07 (7.3) 28 (29.2) 15 (15.6) 03 (3.1) 01 (1) 96 (100)51–60 38 31 (43) 08 (11.2) 15 (20.8) 15 (20.8) 01 (1.4) 02 (2.8) 72 (100)>60 64 55 (46.2) 18 (15.1) 20 (16.8) 17 (14.3) 05 (4.2) 04 (3.4) 119 (100)Total (%) 260 213 (42.6) 62 (12.4) 105 (21) 91 (18.2) 14 (2.8) 15 (3) 500 (100)

Table 2. Age-wise prescribing frequency of parenteral anti-infective agents in females

Age group Total no. ofpatients

Penicillinþcephalosporins

Quinolones Aminoglyco-sides

Antiprotozoal Glycopeptides Others Total no. ofprescriptions

11–20 12 09 (52.9) 03 (17.7) 02 (11.8) 02 (11.8) 01 (5.9) 00 (0) 17 (100)21–30 22 18 (43.9) 05 (12.2) 08 (19.5) 07 (17.1) 03 (7.3) 00 (0) 41 (100)31–40 25 24 (49) 05 (10.2) 12 (24.5) 07 (14.3) 00 (0) 01 (2) 49 (100)41–50 25 21 (44.7) 09 (19.2) 10 (21.3) 07 (14.9) 00 (0) 00 (0) 47 (100)51–60 25 22 (41.5) 05 (9.4) 13 (24.5) 10 (1.9) 02 (3.8) 01 (1.9) 53 (100)>60 31 20 (32.3) 08 (12.9) 16 (25.8) 16 (25.8) 00 (0) 02 (3.2) 62 (100)Total (%) 140 114 (42.4) 35 (13) 61 (22.7) 49 (18.2) 06 (2.2) 04 (1.4) 269 (100)

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parenteral �-lactam antibiotics were cefotaxime (16%)and ceftriaxone (10.53%). Amikacin was the mostcommonly prescribed aminoglycoside (11%). Metro-nidazole was another frequently prescribed antibiotic(17.7%). Among newer agents, augmentin (amoxycil-lin and clavulinate) was more frequently prescribed(4.16%) than cefpirome (0.78%), meropenem (0.52%),teicoplanin (0.52%), etc. (Tables 3 and 4). The totalquantity of parenteral anti-infective agents used in the

emergency unit was 94.08 DDD/100 bed days.Respiratory tract, CNS and abdominal infectionsaccounted for over 60% of anti-infective use(Figure 1). The mean (SD) daily cost of antibioticwas US$3.8 (7.7); median (range) 2 (0.1–85.7).

DISCUSSION

The primary goal of this study was to analyze theutilization of parenteral anti-infective agents in amedical emergency unit. Ours is a tertiary care

Table 3. Prevalence of use of parenteral �-lactam antibiotics

Drugs ATC code Percentage ofprescribingfrequency

DDD/100 beddays

Cefotaxime J01DA10 16.0 13.9Ceftriaxone J01DA13 10.53 9.15Augmentina J01CR02 4.16 8.68Penicillin G J01CE01 3.64 4.4Cloxacillin J01CF02 3.25 5.65Ceftazidime J01DA11 1.82 1.19Cefpirome J01DA37 0.78 0.51Meropenem J01DH02 0.52 0.68Timentinb J01CR03 0.52 0.27Ampicillin J01CA01 0.39 0.34Magnexd Not assigned yet 0.39 NILZosync J01CR05 0.26 0.56Piperacillin J01CA12 0.13 0.08Ceftizoxime J01DA22 0.13 0.11

aAugmentin¼AmoxycillinþClavulanate.bTimentin¼TicarcillinþClavulanate.cZosyn¼ PiperacillinþTazobactam.dMagnex¼CefoperazoneþSulbactam.

Table 4. Prevalence of parenteral use of other individual drugs

Drugs ATC code Percentage ofprescribingfrequency

DDD/100 beddays

Amikacin J01GB06 19.0 12.37Metronidazole J01XD01 17.7 15.37Ciprofloxacin J01MA02 6.5 4.52Levofloxacin J01MA12 5.59 9.72Gentamicin J01GB03 2.21 1.28Vancomycin J01XA01 1.56 1.36Clindamycin J01FF01 1.3 1.13Teicoplanin J01XA02 1.04 0.9Ofloxacin J01MA01 0.52 0.45Azithromycin J01FA10 0.52 0.75Quinine — 0.52 —Streptomycin J01GA01 0.39 0.34Amphotericin J02AA01 0.26 0.16Acyclovir J05AB01 0.26 0.1Fluconazole J02AC01 0.13 0.11

Figure 1. Contribution of various organ system infections to the use of parenteral anti-infective agents

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Copyright # 2004 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2004; 13: 653–657

referral hospital with a total bed strength of about1000. Patients coming to our hospital are referredfrom atleast five different states. This type of hospitalsetting is unique in itself and was chosen for severalreasons. First of all, emergency ward patients havesevere infections requiring immediate parenteralanti-microbial use. Secondly, since the patients arevery sick and exact diagnosis can be known only afterculture-sensitivity report becomes available (whichmay take 24–48 hours), physicians have no choicebut to prescribe broad spectrum anti-microbials oruse them in combinations. Also, factors like patientnon-compliance, storage of drugs at home and spoi-lage are eliminated.5 Furthermore, a preliminary pilotstudy on the use of anti-microbials in emergency unitshowed that a large proportion (76.2%) of patientsrequiring antibiotics receive them as parenteral ther-apy, whereas a further 21.6% received both oral andparenteral therapy.

Average number of drugs per prescription is animportant index of prescription audit. It is preferable tokeep the mean number of drugs per prescription as lowas possible since higher figures always lead toincreased risk of drug interactions, development ofbacterial resistance and increased hospital costs.6 In thepresent study, two anti-microbials were prescribed to alarge number of patients (43.82%). In an emergencyunit, physicians wish to cover a broad anti-bacterialspectrum to cover multiple organisms and to treatnosocomial infections, which if present, can be severeand multidrug resistant. Also, a patient with severeinfection needs immediate treatment without losingtime to culture sensitivity tests, which were done in52% of patients. Still DDD of 98.04/patient/100/bedday is high enough to warrant caution.

Another important aspect in prescribing of anti-microbial is the excessive use of newer and expensivedrugs. This not only affects the cost of the treatmentand compliance but also increases the incidence ofbacterial resistance to newer drugs. In our hospitalsetup need for expensive drugs affects patients’compliance because of their inability to pay for thetreatment. Also, majority of the patients attending theemergency themselves pay for their treatment andhealth insurance coverage is scanty. In the presentstudy, it was observed that newer and expensive anti-microbials like �-lactams, amikacin were frequentlyprescribed. We also found a high tendency to prescribe(43.3%) brand names. The main reasons given forusing brand names were the quality of product and easyavailability. But one should not overlook the costburden put up on patients. We found that expensiveanti-infective costing more than US$ 2/day was used in

7% of patients. The mean (SD) cost/patient/day wasUS$ 7.3 (12.3), median (range) 3.84 (0.1–96.9) whichis enormous for an Indian patient visiting emergencyunit of a tertiary care hospital. The use of expensiveanti-microbials and their combinations could bejustified keeping in mind the severity of infectionsseen in patients admitted in the emergency. The anti-infectives used for the treatment of pneumonia andmeningitis were similar to those advocated in interna-tional guidelines.7–9

Widespread use of third-generation cephalosporins,as observed in our study, has been linked to thedevelopment of extended-spectrum �-lactamase- pro-ducing gram-negative bacteria and to the overgrowth ofenterococcal species (which are not covered by theseagents).10 Reduction in the use of these agents andconcomitant increases in the use of extended-spectrumpencillins and combination therapy with aminoglycosi-des have been shown to restore bacterial susceptibility.11

The prevalence of infectious diseases and microbialresistance might affect the intensity and pattern ofantibiotic use. There are a number of other complexfactors that might influence the pattern of antibiotic usein developing countries like India:12

� difficulty in diagnosing infectious diseases,

� tendency of physicians to treat using a ‘shot-gun’approach,

� prevalent cultural practices and beliefs.

Though at present there are no local practiceguidelines existing in our institute, microbiologicaland anti-infective surveillance data would help inframing guidelines for the use of these agents inemergency ward and the subsequent monitoring ofthese guidelines. Several studies have validated the useof a multidisciplinary, education-based antibiotic-resistance management programs to control anti-microbial resistance.13

In conclusion, this study provides an overview ofparenteral anti-infective use in emergency, studies onwhich are relatively lacking. The study might serve as areference standard for comparing similar pharmacoe-pidemiology data in future.

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4. Furnish statistics on Medicines, Alterations to ATC classifica-tion, valid as of January 2002. National Agency for Medicinesand Social Insurance Institution Helsinki 2002. P.294.

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12. Kunin CM, Lipton HL, Tupasi T, Sacks T, Scheckler WE,Jivani A. Social, behavioural and practical factors affectingantibiotic use world wide: report of task force 4. Rev InfectDis 1987; 9 (Suppl. 3): 270–285.

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