~ Pergamon

Soc. Sci. Med. Vol. 38, No. 5, pp. 717-724, 1994 Copyright © 1994 Elsevier Science Ltd

Printed in Great Britain. All rights reserved 0277-9536/94 $6.00 + 0.00

THE USE OF ANTIMICROBIAL DRUGS IN NAGPUR, INDIA. A WINDOW ON MEDICAL CARE IN A

DEVELOPING COUNTRY

VIKRAM DUA, CALVIN M. KUNIN* and LAURA VANARSDALE WHITE The Department of Internal Medicine, Room M110, Starling Loving Hall, The Ohio State University,

320 West 10th Avenue, Columbus, OH 43210, U.S.A.

Abstract--The objective of the study was to determine the patterns of use of antimicrobial drugs in the general population of the large, industrial city of Nagpur, India. Interviews of pharmacists and clients were carried out in a stratified, random sample of 34 pharmacies to determine beliefs and practices in prescribing and self-prescribing of antibiotics by complaint, choice of drug, dose, duration, cost, age and sex of the consumers.

The study showed that drugs were dispensed without prescription despite prohibition by the Indian Pharmaceutical Act. Sales of antimicrobial drugs accounted for 17.5% of 511 purchases and 23.3% of expenditures for drugs. Proprietary brands of penicillins, co-trimoxazole and tetracyclines were dispensed most often (64.8%). The most common indications were upper respiratory, gastrointestinal and nonspecific complaints. The median number of units obtained was 5.0 (95% range 1-20), at a median cost of $0.50 per purchase, usually taken for less than five days. Repeat purchases were made without consulting a physician. Almost two thirds of purchases (63.9%) were for males, mainly under the age of ten years. Clients had poor knowledge of the indications, side effects, adverse reactions and appropriate duration of therapy. The dispenser viewed himself as a businessman rather than a professional and rarely offered unsolicited advice. Co-prescribing of 'tonics' added to costs and decreased the purchasing power for antimicrobial drugs.

Most purchases of antimicrobial drugs in community pharmacies in Nagpur were for minor indications and were limited by the purchasing power of the consumers. It is doubtful that the choice of drug and the short duration of therapy would be effective for serious infections. The more frequent use of antimicrobial drugs in males may reflect greater susceptibility to infectious diseases and/or sex bias. Constraints of poverty and culture severely limit effective medical care in this city.

Key words--antibiotics, prescription, medical care, India

Bacterial infectious diseases account for much of the morbidity and mortality, particularly among chil- dren, in the developing nations of Asia, Africa and South America [1-3]. Many of these infections can be treated effectively with modern antimicrobial drugs. Essential drugs may be unavailable or expensive, access to medical care is often limited and self- prescribing is common [4]. The underlying problems include severe economic constraints, inadequate health care delivery systems, local customs and beliefs and overzealous promotion of drugs [5-18]. The issues are compounded by the problem of widespread resistance to antimicrobial drugs [19-23].

The use of antimicrobial drugs in developing countries is of profound importance to people living in developed countries. Because of the ease of global travel, the occurrence of resistant microorganisms in one part of the world can have a major impact on the efficacy of antimicrobial therapy in other regions as well as for travelers to these countries.

This report from Nagpur, India is one of a series of studies [24-28] commissioned by the International Clinical Epidemiology Network (INCLEN) to obtain

*To whom all correspondence should be addressed.

quantitative information concerning the use of antimicrobial drugs in representative, developing countries. The major focus of these studies is on purchase of drugs in community pharmacies. This provides an epidemiologic window on the final out- come of decisions by physicians and consumers to use antimicrobial drugs. The goal is to understand the dynamics which lead to these decisions and to de- velop practical methods to improve the availability, delivery and use of therapeutic drugs in developing countries.

METHODS

The study was conducted between October 1988 and March 1989 in Nagpur, Maharastra, India. This is a large industrial city in central India (population 1,219,000, 1981 census). Nagpur was selected because it is said to be a 'typical' Indian city, it has an INCLEN unit at the major teaching hospital and one of the authors (V.D.) spoke the local language. The Nagpur Chemists and Druggists Association agreed to help with the project. This is an elected body which represents all of the 202 pharmacies in the urban Nagpur area. The pharmacies were stratified into

717

718 VIKRAM DUA et al.

three groups according to sales in rupees (Rs). About 16 Rs equaled one U.S. dollar at the time of the study. The stores were divided into those with daily sales of > 3000 Rs, 1500-3000 Rs and < 1500 Rs. A representative sample of 34 (16.8%) of the pharma- cies was selected by a table of random numbers.

Separate structured interview forms were prepared for proprietors and clients. The proprietor forms elicited information concerning the ownership and structure of the business. This included staffing, edu- cation and training of the dispensers, policy concern- ing nonprescription requests for drugs, sources of supply, inventory, record keeping and attitudes towards physicians and customers. The client forms elicited information concerning the nature of the prescribing practitioner or self-prescriber; the demo- graphic characteristics of the purchaser and the per- son for whom the drug was to be used. Detailed information was obtained concerning the complaint, choice of drug, dose, duration, cost, age and sex of the consumers and the purchasers' knowledge and beliefs concerning drugs. The forms were designed in English, translated into Hindi, and back translated to test for validity. This process was repeated twice before the forms were deemed acceptable. The forms were then pre-tested in two stores and appropriate changes were again made. Copies of the question- naires are available on request from the authors.

The first visit to each shop was conducted by one of the authors (V.K.) together with a representative of the Chemists and Druggists Association. The owners were made aware of the purpose of the study and their cooperation was requested. There were no refusals to participate. The proprietor or his represen- tative was then interviewed in an open, informal manner concerning the operations of the business and views on the system of use of drugs in the community. A second visit was arranged during the evening business hours. During this visit a structured inter- view was carried out with the most senior of the personnel present. Sales in each store were observed on one evening for a period of 4-5 hr. Each client who requested an antimicrobial drug, with or without a prescription, was interviewed in the vernacular Hindi after being introduced by the proprietor and after verbal consent was obtained. About 15 clients were interviewed at each store. Each interview lasted about 15 min. Information was obtained on the pur- chase of all drugs. Interviews with clients was limited to those who requested oral or injectable, antibacte- rial drugs for systemic use. Topical, vaginal, oph- thalmic, otic, antimalarial, antileprosy, antiparasitic and antifungal drugs are not included in this report because the focus was on systemic antibacterial drugs and the number of requests for these other agents was small.

The data from the structured forms were recorded in Hindi. They were translated into English and checked for accuracy by a third person not directly involved in the interviews. The data were then entered

into a DBase I I I+ database management program using standardized codes. The data were then im- ported into the EpiInfo (Center for Diseases Control, Atlanta, Ga) statistical analysis program and un- coded, regrouped, tabulated and analyzed.

RESULTS

Indian pharmaceutical laws

Sales of pharmaceuticals falls within the scope of the Indian Pharmaceutics and Cosmetics Act. Ac- cording to this law antimicrobial drugs are not to be dispensed to individuals without a valid, current prescription from an allopathic physician (one who is trained according to Western scientific methods) and may not be refilled unless specific instructions are provided. Records are to be kept for three years of the supply and dispensing of all scheduled drugs, including the name of the patient. The penalty for violation is suspension or revocation of license. Brand substitution is illegal in India. Two drugs, cimetidine and bromhexine, were available as generic products only at the time of the study.

Characteristics of the pharmacies and dispensers

The stores were small, family businesses. There were no significant differences among the three econ- omic levels of pharmacies in patterns of dispensing drugs. Drugs were sold to clients whether or not they had a prescription. All the dispensers were males. Two thirds (65.4%) claimed to be 'registered pharma- cists' with college level training in pharmacy. They reported that their prime source of continuing edu- cation was from pharmaceutical company sales repre- sentatives and occasionally from physicians (13% of respondents). Inventories were kept at a minimum by daily purchases from a 'wholesaler's market' or at times from other retailers. Occasionally, promotional purchases were made directly from the manufactur- ers. Prescriptions were retained by the patient and could be used repeatedly, except for narcotics and barbiturates. Most medications were provided in foil or paper leafs. Package inserts often came with the boxes of leafs, but were never requested during the period of observation.

Attitudes of pharmacists toward the pharmaceuticals law

The shops ignored the law and dispensed drugs for prescriptions from non-allopathic physicians and by self-request. No incident of legal regulation was observed. The pharmacists believed that even if an attempt were made to enforce the law it would be virtually impossible to regulate because of the very large number of small stores. The general attitude towards laws in Indian society is that regulations could be bypassed by influence and money. Laws were seen as tools to punish an individual for an offense unrelated to the charge.

Use of antimicrobial drugs in Nagpur, India 719

Attitudes of pharmacists toward physicians

The pharmacists admired the physicians for their earning power. Some physicians were viewed as as- tute or clever. Others were considered as 'idiots' for writing a particular prescription. Many pharmacists said they did not think about or care how a physician prescribed as long as they obtained his business, but some expressed the view that lack of controls over dispensing was not in the best interest of the patients. The pharmacists were aware that physicians obtained perquisites from the pharmaceutical companies. They viewed the practice of providing refrigerators, cabi- nets, samples and office supplies to physicians as business commissions for prescribing specific prod- ucts. The concept of professionalism was not strong in this society.

Many pharmacists complained about the need to maintain inventories of a large number of brands of identical medications. This was considered to be necessary to maintain good relations with the phys- icians, Drug company representatives were observed visiting the pharmacies to check on whether phys- icians prescribed their products. Pharmacists would not substitute another product when a particular brand was not available. They would either turn the customer away or go to a nearby retailer to procure the product. On occasion the pharmacist would ask the client to request the prescriber to change the brand.

The general attitude of pharmacists was that if they refused an improper script it would be filled by another pharmacy. We encountered only one in- stance in which a pharmacist refused to fill what he believed to be an improper prescription by a phys- ician. This was for four tablets of a beta blocker.

Characteristics of the prescribers

Most of the prescriptions were from allopathic practitioners, but many were prescribed by those in other medical disciplines, Table !. Self-prescribing, or selection of a drug by the pharmacist was common

Table 1. Source of 511 requests with or without prescriptions for systemic antimicrobial drugs at pharmacies in Nagpur, India

A. By prescription Prescriptions

Prescribed by* No. (%) (%)

AIIopathic physicians 313 61.3 81.3 Non-allopathic physicianst 42 8.2 10.9 Paramedicals 18 3.6 4.7 Dentists 12 2.3 3. I Subtotal 385 75.3 100.0

B. Without prescription Requests Ordered by*

Pharmacist 15 2.9 11.9 Self-prescribed 111 21.7 88.1 Subtotal 126 24.7 100.0

Total purchases 511 100.0

*Percent of individuals who ordered the drug. "f'These include 25 Hindu (Ayuravedic), 16 homeopaths and 1

Muslim (Unani).

~ 100

a. 8 0

[ n,

40

2o

m

z I I I I I I I I

<10 I0 20 30 40 50 60 70

AGE IN YEARS

Fig. 1. Number of purchases of antimicrobial drugs in pharmacies in Nagpur, India in relation to the age and sex

of the consumer.

(24.7%). The frequency of self-prescribing was un- doubtedly much higher than shown in the table since 2.7% of clients submitted old, reused prescriptions and many of the prescriptions permitted refills.

Characteristics of the purchasers and consumers

The clients were considered to be representative of people who purchased drugs in this community be- cause of the sampling method and large number of observations. Detailed demographic characteristics could not be obtained because of the brief time available for each interview. Most of the purchases (71.6%) were made for another member of the im- mediate family. The age and sex of the consumer were available for 482 (94.3%) of the 511 encounters (Fig. 1). The purchases were more likely to be for a male patient (63.9%) at all ages. Many of the pur- chases were for children under the age of ten (26.1%). The sex differential favoring males was greatest among infants and children and least for patients over 50 years of age.

Client knowledge and beliefs

The clients demonstrated very limited knowledge of the type of medication purchased, the potential side effects and the exact dosage and duration of therapy. Among the 511 encounters 476 (93.0%) did not know the type of medication being prescribed. Only 3.5% were aware that an antimicrobial agent was to be used. In addition, 481 (94.1%) were unaware that the medications had side effects. Only 12 (2.3%) of clients were aware that allergic reactions were possible and all of these were physicians. In only 2.5% of the 511 encounters did the client seek the advice from the dispenser concerning dose, duration or frequency of administration. The dispenser offered unsolicited advice concerning use of the medication in only 18 (3.5%) of the encounters,

The 111 clients who obtained antimicrobial drugs without prescription were asked "Who advised you

720 VIKRAM DUA et al.

to take this medicat ion?". The following responses were obtained:

(1) An al lopathic physician had previously advised use of the p roduc t for a similar compla in t (42.3%);

(2) a medical pract i t ioner had given them a 'ver- bal ' prescr ipt ion (33.3%);

(3) it was advised by ano the r person or could not recall (17.1%); and

(4) the client was a physician (7.2%).

Clients commonly justified their self-prescribing behav ior by stat ing tha t "Wheneve r I get these symptoms, and I go to a doctor , he gives me the same medicine and charges me 10 rupees. So why not just buy the medicine?"

There was a s trong belief among many of the clients tha t a person ' s innate ' s t rength ' and 'weak- ness ' are causat ive features of all illnesses. Hence, it was not surpris ing to learn, in informal interviews with pract i t ioners, tha t the consumer would not be satisfied unless ' body s t rengthening ' medicat ions were included with the prescript ion for an ant imicro- bial drug. These beliefs, together with the relatively high costs of the addi t ional ' tonics ' and limited purchas ing power, cont r ibu ted to the relatively small n u m b e r of ant imicrobia l drugs tha t were purchased at a given visit.

Characteristics of requests and sales

Antimicrobia l drugs accounted for 17.5% of all purchases and 23.3% of sales in rupees. A b o u t hal f the t ime (52.8%) ano the r drug was also purchased. These were usually analgesics, v i tamin and mineral prepara t ions and ' tonics ' . Usually only one ant ibiot ic

was purchased at a time, but in 7.0% of instances two different ant ibiot ics were obtained.

Selection of antimicrobial drugs

The dis t r ibut ion of the ant imicrobia l drugs accord- ing to class purchased with or wi thout prescript ion is shown in Table 2. Aminopenici l l ins (mainly ampi- cillin and amoxicillin) were requested most com- monly, followed by co-t r imoxazole and tetracyclines. Most were oral prepara t ions , but 6.8% were par- enteral drugs, mainly gentamicin and cefazolin. Brand names were requested 94.1% of the time. Combina t i on products (excluding co-tr imoxazole) made up 13.7% of purchases. Antituberculous drugs were purchased 6.1% of the time. Of these purchases 58.1% was obtained either without prescription or with a reused prescription. When asked for advice, the pharmacis ts r ecommended use of tetracyclines 53.3% of the time. Six of the 78 (7.7%) purchases of tetracycline were by physician prescr ipt ion for chil- dren under the age of 15 years.

Indications for which antimicrobial drugs were pur- chased

The clinical problems for which ant imicrobia i agents were purchased are shown in Table 3. Nearly one th i rd of these (164) were for respiratory com- plaints. Ant ibiot ics were prescribed commonly for nonspecific compla in ts such as fever, const i tu t ional symptoms, abdomina l pain, diarrhea, skin and soft tissue infections. Six percent of the 385 physician prescript ions and 2.9% of the 111 self-prescriptions were for condi t ions for which the efficacy of ant imi- crobial agents is highly quest ionable. These included

Table 2. Purchases ot" systemic antimicrobial drugs over a 3 hr period of observation in 34 pharmacies in Nagpur, India

Total With written Without purchases prescription prescription

No. % No. %* No. %*

A. All drugs Penicinins 155 30.3 115 74.2 40 25.8 Co-trimoazolet 98 19.2 69 70.4 29 29.6 Tetracyclines 78 15.3 51 65.4 27 34.6 Anti-diarrheals~ 65 12.7 48 73.8 17 26.2 Anti-t uberculous 31 6.1 13 41.9 18 58.1 Macrolides 27 5.3 23 85.2 4 14.8 Cephalosporins 24 4.7 23 95.8 1 4.2 Chloramphenicol 19 3.7 16 84.2 3 15.8 Aminoglycosides 5 1.0 5 100.0 0 0.0 Urinary antiseptics 5 1.0 4 80.0 1 20.0 Fluoroquinolones 4 0.8 4 100.0 0 0.0 Total 511 100.0 371 72.6 140 27.4

B. Penicillins only Aminopenicillins 124 80.0 97 78.3 27 21.7 Natural (G&V) 19 12.3 3 36.8 12 63.2 Pen'aset 12 7.7 I 1 91.7 1 8.3 Penicillins 155 100.0 115 74.2 40 25.8

*Percent of total prescriptions for each. t Penicillinase-resistant penicillins. SThese products contained various mixtures of metronidazole, tinidizole, kaolin, pectin,

attapulgite, atropine, diphenoxylate, furazolidine, streptomycin, iodochlorohydrox- yquinone, diloxinide furoate and aluminium hydroxide.

Use of antimicrobial drugs in Nagpur, India

Table 3. Complaints, as indicated by purchaser, for which a systemic antimicrobial drug was requested in Nagpur, India

Compla in t No. % No. %

Respiratory 164 32.1 Upper tract 116 22.7 Throat 22 4.3 Chest 20 3.9 Ear 6 1.2

Gastrointestinal 71 13.9 Abdominal pain 38 7.4 Diarrhea 31 6. I Post-surgical 2 0.4

Systemic 63 12.3 Fever 46 9.0 Constitutional 17 3.3

Skin & Soft Tissue 60 11.7 Acne, skin ulcers 28 5.5 Wound prophylaxis 24 4.7 Other skin problem 6 1.2 Joint pain 2 0.3

Other, not specified 59 11.5

Genito-urinary 41 8.0 Urinary tract 16 3.1 Post-surgical 13 2.5 Suspected STD 12 2.3

Dental or oral 30 5.9

Tuberculosis 23 4.5

Total 511 100.0 511 100.0

constipation, dysmenorrhea, peptic ulcer disease, anorexia, myalgia, edema and fatigue.

Cost and quantity of purchases

The median cost per unit (pill, capsule or ampule) was 1.4Rs or about U.S.$0.09 (95% range 0.3-8.3 Rs). Only about 10% of purchases were for drugs costing more than 4 Rs per unit. The median cost per prescription was 8.0 Rs or about U.S.$0.50 (95% range 1.2-54 Rs). As the cost of a prescription increased fewer units were purchased. When the total cost exceeded 50Rs (U.S.$3.13) only 62.1% were filled. When a non-antibiotic was purchased at the same time (on 271 occasions) the cost of the antimi- crobial drug never exceeded 50 Rs. Thus, additional high cost prescriptions had a negative effect on purchase of the complete amount of antimicrobiai drug which was prescribed.

Of the purchases for individual use, excluding those for treatment of tuberculosis, most (86.1%) were for 10 units or less, Fig. 2. Fewer units were purchased than prescribed, median 5.0 (95% range 1-20) vs median 6.0 (95% range 1-21), respectively. The number of units dispensed were greater when prescribed by a physician than when self-prescribed. The median number of units dispensed for 362 pre- scriptions was 6.0 (95% range 1-20) whereas the median number dispensed without prescription in 136 instances was only 4.0 (95% range 1-12). Most of the purchases of the more expensive antibiotics were ordered by physicians and were often accompanied by a prescription for another drug.

721

Repeat purchases

The clients tended to spread out purchases at intervals of several days. Many of the purchases (138/511, 27.0%), were used to complete a few more days of a previous course of therapy. About two thirds (69.7%) of these were for continuation of therapy within 24 hr of the last dose taken. Many of these renewals (38.4%) were for less than a two day c o u r s e .

Duration of use

It would be expected from the number of units dispensed that most courses of antimicrobial therapy would be quite short. Most of the 371 current pre- scriptions (50.1%) were for less than five days, 22.4% were for 5-14 days, and only 2.7% were for more than 14 days. About a quarter of the time (24.8%) the prescriptions did not state the duration of therapy.

Changes made to the initial request

The major reason for change in a prescription was inability or unwillingness to pay for the complete amount of drug prescribed at time of the transaction. Most prescriptions were dispensed exactly as pre- scribed (69.1%) and only three were not filled. Of the 155 requests for a change, most (73.5%) were for a lower quantity. Only two were for a greater quantity. There was a change in brand in 16.1%; a change in agent in 1.9%; a change in dosage in 1.9% and some combination of the above in 5.2%. Six percent of consumers expressed the desire to 'test' the medi- cation first to see if it provided relief before filling the remainder of the prescription.

60

5O

,~ 4C

b. 3C 0

U 211

I0

I - 5 6-10 11-15 16-20 21-35 I - 5 6-10 11-15 16-20 21-35 UNITS REQUESTED UNITS DISPENSED

Fig. 2. The number of units of antimicrobial drugs which were originally requested by individuals compared to those actually dispensed in pharmacies in Nagpur, India. The data are for 498 requests, including 362 with prescriptions and 136 self-prescribed. Thirteen purchases for physician's in- ventory or for treatment of tuberculosis are not included

here.

722 VIKRAM DUA et al.

Previous use o f antirnicrobial drugs' for the same complaint

Among the 511 interactions 128 of the clients (25.1%) indicated that they had taken a different medication previously for the same complaint. Most of the changes (64.1%) were made by the original practitioner; some clients (26.5%) had changed prac- titioners and a few (9.4%) changed their own self-pre- scribed medication. Most of the clients (58.6%) did not know what drug had been used previously; some (19.5%) knew that a different antibiotic had been used; and some (21.9°,/0) had been treated previously with a non-antimicrobial drug.

Comparison with practices at an out-patient pharma~\v (~/a large city hospital

The dispensing of drugs was observed in the phar- macy of a large government hospital. There were a number of windows in the waiting room which were labeled 'General', "Pediatrics', 'Costly Drugs" and other categories. The scripts from physicians pro- vided detailed information on drug, dose, frequency and quantity as well as the diagnosis. Almost all agents were dispensed for a maximum period of three days or for seven days if the patient had been seen in specialty clinics such as cardiology, tuberculosis or epilepsy. There were no automatic refills and the patient had to return to the physician to obtain a new prescription. The patient kept the prescription and had the option to obtain the drug from a private pharmacy. The drugs were dispensed into folded papers without identification. Advice was not offered concerning the drug or how it should be used. Drug shortages occurred frequently and were an important reason for limiting dispensing to only three days. On one visit the pharmacy did not have a supply of ampicillin or co-trimoxazole. The patient had to return to the physician for another drug or purchase it privately. Prescription of other drugs along with the antibiotic was common. These were usually for vita- mins, antacids and antipyretics.

DISCUSSION

The findings in this study of pharmacy practices in Nagpur~ India, are consistent with similar studies conducted in other developing countries [24-34]. Physicians see as many patients as possible in the shortest period of time with minimal, if any, labora- tory and radiologic support. The pharmacies work on small profit margins and the patients are constrained by economic deprivation and cultural beliefs. There is a high frequency of self-prescribing; the number of units purchased are inadequate to treat serious infec- tions; most prescriptions are for brand name and combination products; there is often simultaneous purchase of nostrums containing mixtures of costly drugs of doubtful efficacy; tetracyclines continue to be prescribed for children: ineffective and potentially

toxic agents are purchased for treatment of diarrhea and antimicrobial drugs are used for inappropriate indications.

A striking finding in Nagpur was the more frequent purchase of antimicrobial drugs for males rather than females. This may be due to a greater fiequency of the clinical manifestations of many bacterial infectious diseases in young male children [35[. It may also reflect preference for male children and sex bias which favors provision of food and health care to males in the Indian subcontinent [36, 37].

It is doubtful that antimicrobial drugs were used effectively in Nagpur. The most commonly used drugs, aminopenicillins and co-trimoxazole, are effec- tive against many of the bacteria which produce lower respiratory infections, including Streptococcus pneumoniae and Hemophilus inltuenzae. However, most of the respiratory infections for which they were used were minor and self-limited. The ,;mall quan- tities of units purchased and the shor! duration of therapy were probably inadequate for the treatment of the more serious infections. It is also doubtful that 'blind' use antimicrobial drugs would be effective for treatment of a wide variety of nonspccific complaints such as fever, abdominal pain, diarrhea and supcrli- cial skin diseases.

It can be argued some individuals might benefit, even from inappropriate therapy, by prevention o/ suppurative otitis media, mastoiditis, mcningitis and pneumonia and by specific treatment of some readily diagnosed infectious diseases. This remains to bc determined. Simple clinical signs can be used to diagnose acute lower respiratory tract infections and determine the need for treatment [381. For example. a community-based, case-management, intervention trial, using locally trained personnel, conducted in Gadchiroli, Maharastra, India [39], was effective in reducing pneumonia and total childhood mortality. In this study cotrimoxazole was targeted for symp- tomatic children with severe, lower respiratory illness who would benefit the most. Cotrimoxazole has also been reported to be as effective as procaine penicillin and ampicillin in treatment of community-acquired pneumonia in Gambian children [40]. These advances may prove to be short lived. In a recent survey in Pakistan [41] among 87 bactcremic strains of S. pneumoniae isolated from children with acute lower respiratory infections 31% were fully resistant to co-trimoxazole and 39°,/o were resistant to chloram- phenicol. Resistance of enteric and urinary pathogens to trimethoprim, the major component of co-trimox- azole, is common in South India and in other devel- oped countries and the combination is not without side-effects [42-47].

The inappropriate use of antimicrobial drugs in distant places such as Nagpur and other parts of the developing world have important implications for the health of people in the developed countries. The ease of travel increases the potential for spread of plasmid- mediated, multiply-resistant bacteria throughout the

Use of antimicrobial drugs in Nagpur, India 723

world. Resistance to antibiotics is a major problem in developing countries. Travelers, even though not taking prophylactic antibiotics, are at increased risk of enteric colonization with indigenous resistant bac- teria [48].

The overzealous marketing of drugs by large, multinational pharmaceutical companies and local firms is responsible, in part, for the large number of proprietary products and inappropriate use of drugs in developing countries [6, 10, 14, 49, 50]. These mar- keting practices have been challenged by advocacy groups such as Health Action International, The Alliance for the Prudent Use of Antibiotics [23] and the Medical Lobby for Appropriate Drug Marketing [50]. Nevertheless, although pharmaceutical compa- nies can create demand for their expensive propri- etary products, sales depend on prescribing by physicians and the demand for drugs by consumers.

It is doubtful that legal remedies would be helpful in Nagpur. Pharmacists sold drugs without prescrip- tion with impunity despite prohibition by the Indian Pharmaceutical Act. We believe, therefore, that the major focuses of attention for the future need to be on a national policy to license a more limited number of safe and effective drugs and on improving phys- ician and consumer knowledge and behavior to use these valuable drugs more rationally. These goals should be very difficult to accomplish even with major changes in the economy and education systems. Guidelines for antibiotic use by practitioners may be helpful. Harvey and his colleagues have shown that they are effective in Australia [51]. The W H O Drug Action Programme is working with countries to rationalize drug supply and use [52-54]. A pilot physician education program in Sri Lanka has re- ported some success [55].

New and more expensive agents are continuously being developed to improve therapy and address the problem of resistant microorganisms. Most people in the developing countries cannot afford these new drugs and resistance is expected to emerge rapidly. It is likely, therefore, that the situation will get worse unless major efforts are made to improve the use of antimicrobial drugs worldwide.

Acknowledgement--This study was supported by Grant RF 87006 No. 93 from the International Clinical Epidemi- ology Program (INCLEN) of the Rockefeller Foundation.

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