Eur J Clin Pharmacol (1991) 41:85-87 0031697091001792
@Be¢ eceEe@@ © Springer-Verlag 1991
Editorial
Antibiotics policies in the developing world A. J. Smith 1, J. K. A r o n s o n 2, and M. T h o m a s 3
1 Department of Clinical Pharmacology,Royal NewcastleHospital, The Universityof Newcastle,Newcastle,Australia 2 MRC Unit and UniversityDepartment of Clinical Pharmacology,RadcliffeInfirmary, Oxford, UK 3 Department of Clinical Pharmacology,Christian Medical College and Hospital, Vellore, India Received: November 2, 1990 Key words" Antibiotics, developing countries, guidelines, local antibiotics policies
Although clinical pharmacologists are by definition interested in all classes of drugs, some drugs seem to be more interesting than others. For example, of the 131 articles published in volume 37 of the The European Journal of Clinical Pharmacology the main systems affected by the classes of drugs studied were the cardiovascular system (32% of cases), the central and peripheral nervous systems (19%), and the endocrine system (including metabolism) (18%). To some extent this parallels the use of drugs in Europe, but it is none the less disappointing to see antiinfective drugs coming a poor fourth, taking only 9% of the share (12 articles, 7 of which were about pharmacokinetics). This relative lack of interest in anti-infective drugs does not only apply to their pharmacological actions, since it is certainly the case that clinical pharmacologists have also played a relatively minor role in the surveillance and regulation of anti-infective drugs world-wide. For example, in 1987 the journal Reviews of Infectious Diseases, in a supplement to Volume 9, published reports from six Task Forces which had been commissioned by the Fogarty International Centre of the National Institutes of Health to advise on 'Antibiotic use and antimicrobial resistance world-wide' [1]. Although several clinical pharmacologists served on individual Task Forces, the majority of the members came from microbiology, internal or preventive medicine, and epidemiology. Yet anti-infective drugs are amongst the most widely used classes of drug in the world, accounting for over 25% of drug costs in many hospitals and for an unknown but almost certainly higher proportion of prescriptions in the community, especially in the developing world. Surveys of their use from many countries - both developed and developing - have repeatedly emphasized the fact that inappropriate use of anti-infective drugs is widespread. Moreover, this misuse is uniquely dangerous, in that it results not only in the mistreatment of patients, but also in an ad-
verse effect on the pathology of infectious diseases, by altering the microbial environment at the same time. Despite sporadic efforts, there are very few examples of strict regulation of the use of anti-infective drugs. Some larger hospitals have firm policies governing the use of particularly useful and/or expensive drugs, but in relatively few communities is there any regular audit of antibiotic use outside hospitals or any attempt to formulate and monitor therapeutic policies. However, the growing problem of bacterial resistance and the limits imposed by shrinking health budgets are gradually obliging us to abandon our complacency and to address the very real problems of a world-wide plethora of antimicrobials coupled with unbridled and uncritical use. Against this background, a two-day conference on 'Rational Use of Antibiotics', held at the Christian Medical College Hospital in Vellore, South India in April 1990, was timely. Organized by members of the Department of Clinical Pharmacology of the Medical College, the conference, held in the heat of early summer in South India, brought together medical staff and clinical scientists from many major centres in India, together with guest speakers from European and other countries, all of whom had had personal experience of some aspect of the evaluation or regulation of antibiotic use. The declared objective of the organizers of the conference was to move towards the development of basic guidelines for the use of antibiotics, guidelines which might be applicable to most situations in the Indian subcontinent. However, it soon became clear that many problems were emerging which could not be answered on the spot. Firstly, for whom should guidelines be formulated? In the Western world the answer is straightforward. Guidelines are for the prescriber, who can be clearly defined and is almost invariably medically qualified. In a country of more than 800 million people, the majority of whom live in rural communities served by health workers, themselves often not medically trained, guidelines must be sufficiently simple to be applied by any, whatever their training, who dispense antibiotics.
86 Secondly, by whom should guidelines be formulated? It follows from the need to formulate guidelines for a wide range of different users that the development of guidelines should be in the hands of those who have specialized knowledge but who are not so detached from the realities of community practice that their advice is irrelevant and therefore doomed to be unheeded. Experience in the use of antibiotic policies in Oxford suggests that policies are more likely to be applied effectively if individual groups of users, e.g. surgeons, obstetricians, and geriatricians, develop a sense of 'ownership' by formulating their own sets of guidelines in consultation with microbiologists and clinical pharmacologists, even though in such cases it often happens that the guidelines formulated by different groups turn out to be very similar. In contrast, experience elsewhere suggests that policies which are handed down to practitioners by anonymous committees are less likely to succeed. However, it has to be recognized that in large developing countries it may be difficult to mobilize local opinion to a sufficient degree to succeed in the formulation of individual sets of guidelines, and compliance with policies formulated by hospitals on behalf of the community may be difficult to achieve. Thirdly, what is to be the basis for a set of guidelines? The purist would argue that lists of recommended compounds should consist of only those drugs for which good controlled evidence is available. But how do we interpret contradictory studies or make recommendations where no good clinical trials have ever been performed? A workable, if less satisfactory, compromise is the consensus approach which has worked effectively in some countries. Guidelines should also take into account comparative safety and costs. Even if it proves possible to reach an acceptable consensus in relation to local antibiotic policies, all is not won. For example, it is probably inappropriate to introduce a new strategy if its efficacy cannot be monitored. The routine evaluation of new interventions is not yet standard practice in the health departments of even the most developed countries, and it is a tall order to expect that the necessary pre- and post-intervention surveys could be carried out in a comprehensive way in countries such as India, although surveys at a local level could certainly be a marker of the effectiveness of a new policy. The world of antibiotics moves fast and the preparation of guidelines is not a one-off task. Constant revision is required, and this demands dedicated staff, who have to be paid. There can be little doubt that adherence to a carefully-prepared set of antibiotic guidelines can be cost-effective [2, 3], but obtaining the initial injection of money into a guideline programme usually requires independent funding, commonly from government sources, as academic institutions or hospitals rarely have spare resources to divert in this direction. This is one project that is unlikely to be funded by the manufacturers of antibiotics, and in any case antibiotic policies should be seen to be independent and not compromized in any way. Another method of reducing expenditure on antibiotics may be by providing information about drug costs when issuing the results of antibiotic sensitivities [4], although it is not clear what effect this strategy has on the quality of treatment.
A. J. Smith et al.: Antibiotics policies In addition to a thorough discussion of these problems during the conference, five treatment areas were examined in some detail in order to establish whether or not consensus was remotely possible. For simple urinary tract infections it appeared that the quinolones were fast winning the day in India, although not necessarily appropriately. The adoption of the World Health Organization classification of acute respiratory infection emerged as a logical basis for deciding on the need for antibiotics, particularly as sputum culture cannot be relied upon to give clear microbiological guidance. Fever of short duration, commonly diagnosed in India, withered as a category, and no-one doubted the need for accurate diagnosis and the best microbiological evidence before embarking on antibiotic treatment in all but desperate cases. However, it was noted that in general practice antibiotics are extensively misused in such cases. The role of prophylactic antibiotics in surgical wound infection, an area in which good evidence is available from randomized controlled clinical trials, was debated in some depth. Last to be discussed was pyogenic meningitis, a common illness in India and one in which antibiotic sensitivities of causative organism have changed over the past few years. The availability of many drugs over the counter without prescription and an inadequate emphasis on patient education were recognized as major factors militating against the better use of antibiotics. The influence of advertizing was also highlighted in a presentation which contrasted the information provided by pharmaceutical companies for prescribers of the same drugs in Western countries and in India. Almost uniformly, the advertized indications for antibiotics were wider in India, while notes on contra-indications and adverse effects were much more detailed in information provided to Western prescribers. Clearly in some cases there are double standards. Although the conference focussed on antibiotics it was forcefully reminded that the management and prevention of infections must be seen in a wider context. Adequate water supplies, health education, and improvements in hygiene might make a greater impact on the prevalence of some infections than any antibiotic policy. As we left the conference hall and the campus of the Christian Medical College Hospital it was difficult not to notice the roadside stalls which are so much a feature of Indian life. Many purvey antibiotics - of varying quality, one suspects - in single or multiple doses. If introducing and giving effect to antibiotic policies is difficult in the developed countries of the world, how much more difficult is it in developing countries, where so many economic and commercial counter-pressures co-exist and where regulation is so much less effetive. One thing is certain. Clinical pharmacoligists cannot stand aloof from legitimate concerns about the worldwide use and abuse of anti-infective drugs. If we do, we will be justly criticised for being perfectly prepared to devote the resources of our laboratories and units to the investigation of 'me-too' compounds, while being unwilling to be involved in the urgent task of examining drug use in the real world and adding our weight to those trying to improve things.
A. J. Smith et al.: Antibiotics policies
References 1. Levy SB, Burke JR Wallace CK (eds) (1987) Antibiotic use and antibiotic resistance worldwide: report of a study sponsored by the Fogarty Internationel Center of the National Institutes of Health, 1983-86. Rev Inf Dis 9: Suppl 3 2. Friesen WT, Hekster CA, van der Kleijn E (1981) Drug utilization studies in a hospital: the interpretation of record-linked data and the effect of therapeutic audit on drug usage. Aust J Hosp Pharm 11:40-46 3. Landgren FT, Harvey KJ, Mashford ML, Moulds RFW, Guthrie B, Hemming M (1988) Changing antibiotic prescribing by educational marketing. Med J Aust 149:595-599
87 4. Rubinstein E, Barzilai A, Segev S, Samra Y, Modan M, Dickerman O, Haklai C (1988) Antibiotic cost reduction by providing cost information. Eur J Clin Pharmacol 35:269-272
Dr. J. K. Aronson MRC Clinical Pharmacology Unit Radcliffe Infirmary Woodstock Road Oxford OX2 6HE, UK
@Be¢ eceEe@@ © Springer-Verlag 1991
Editorial
Antibiotics policies in the developing world A. J. Smith 1, J. K. A r o n s o n 2, and M. T h o m a s 3
1 Department of Clinical Pharmacology,Royal NewcastleHospital, The Universityof Newcastle,Newcastle,Australia 2 MRC Unit and UniversityDepartment of Clinical Pharmacology,RadcliffeInfirmary, Oxford, UK 3 Department of Clinical Pharmacology,Christian Medical College and Hospital, Vellore, India Received: November 2, 1990 Key words" Antibiotics, developing countries, guidelines, local antibiotics policies
Although clinical pharmacologists are by definition interested in all classes of drugs, some drugs seem to be more interesting than others. For example, of the 131 articles published in volume 37 of the The European Journal of Clinical Pharmacology the main systems affected by the classes of drugs studied were the cardiovascular system (32% of cases), the central and peripheral nervous systems (19%), and the endocrine system (including metabolism) (18%). To some extent this parallels the use of drugs in Europe, but it is none the less disappointing to see antiinfective drugs coming a poor fourth, taking only 9% of the share (12 articles, 7 of which were about pharmacokinetics). This relative lack of interest in anti-infective drugs does not only apply to their pharmacological actions, since it is certainly the case that clinical pharmacologists have also played a relatively minor role in the surveillance and regulation of anti-infective drugs world-wide. For example, in 1987 the journal Reviews of Infectious Diseases, in a supplement to Volume 9, published reports from six Task Forces which had been commissioned by the Fogarty International Centre of the National Institutes of Health to advise on 'Antibiotic use and antimicrobial resistance world-wide' [1]. Although several clinical pharmacologists served on individual Task Forces, the majority of the members came from microbiology, internal or preventive medicine, and epidemiology. Yet anti-infective drugs are amongst the most widely used classes of drug in the world, accounting for over 25% of drug costs in many hospitals and for an unknown but almost certainly higher proportion of prescriptions in the community, especially in the developing world. Surveys of their use from many countries - both developed and developing - have repeatedly emphasized the fact that inappropriate use of anti-infective drugs is widespread. Moreover, this misuse is uniquely dangerous, in that it results not only in the mistreatment of patients, but also in an ad-
verse effect on the pathology of infectious diseases, by altering the microbial environment at the same time. Despite sporadic efforts, there are very few examples of strict regulation of the use of anti-infective drugs. Some larger hospitals have firm policies governing the use of particularly useful and/or expensive drugs, but in relatively few communities is there any regular audit of antibiotic use outside hospitals or any attempt to formulate and monitor therapeutic policies. However, the growing problem of bacterial resistance and the limits imposed by shrinking health budgets are gradually obliging us to abandon our complacency and to address the very real problems of a world-wide plethora of antimicrobials coupled with unbridled and uncritical use. Against this background, a two-day conference on 'Rational Use of Antibiotics', held at the Christian Medical College Hospital in Vellore, South India in April 1990, was timely. Organized by members of the Department of Clinical Pharmacology of the Medical College, the conference, held in the heat of early summer in South India, brought together medical staff and clinical scientists from many major centres in India, together with guest speakers from European and other countries, all of whom had had personal experience of some aspect of the evaluation or regulation of antibiotic use. The declared objective of the organizers of the conference was to move towards the development of basic guidelines for the use of antibiotics, guidelines which might be applicable to most situations in the Indian subcontinent. However, it soon became clear that many problems were emerging which could not be answered on the spot. Firstly, for whom should guidelines be formulated? In the Western world the answer is straightforward. Guidelines are for the prescriber, who can be clearly defined and is almost invariably medically qualified. In a country of more than 800 million people, the majority of whom live in rural communities served by health workers, themselves often not medically trained, guidelines must be sufficiently simple to be applied by any, whatever their training, who dispense antibiotics.
86 Secondly, by whom should guidelines be formulated? It follows from the need to formulate guidelines for a wide range of different users that the development of guidelines should be in the hands of those who have specialized knowledge but who are not so detached from the realities of community practice that their advice is irrelevant and therefore doomed to be unheeded. Experience in the use of antibiotic policies in Oxford suggests that policies are more likely to be applied effectively if individual groups of users, e.g. surgeons, obstetricians, and geriatricians, develop a sense of 'ownership' by formulating their own sets of guidelines in consultation with microbiologists and clinical pharmacologists, even though in such cases it often happens that the guidelines formulated by different groups turn out to be very similar. In contrast, experience elsewhere suggests that policies which are handed down to practitioners by anonymous committees are less likely to succeed. However, it has to be recognized that in large developing countries it may be difficult to mobilize local opinion to a sufficient degree to succeed in the formulation of individual sets of guidelines, and compliance with policies formulated by hospitals on behalf of the community may be difficult to achieve. Thirdly, what is to be the basis for a set of guidelines? The purist would argue that lists of recommended compounds should consist of only those drugs for which good controlled evidence is available. But how do we interpret contradictory studies or make recommendations where no good clinical trials have ever been performed? A workable, if less satisfactory, compromise is the consensus approach which has worked effectively in some countries. Guidelines should also take into account comparative safety and costs. Even if it proves possible to reach an acceptable consensus in relation to local antibiotic policies, all is not won. For example, it is probably inappropriate to introduce a new strategy if its efficacy cannot be monitored. The routine evaluation of new interventions is not yet standard practice in the health departments of even the most developed countries, and it is a tall order to expect that the necessary pre- and post-intervention surveys could be carried out in a comprehensive way in countries such as India, although surveys at a local level could certainly be a marker of the effectiveness of a new policy. The world of antibiotics moves fast and the preparation of guidelines is not a one-off task. Constant revision is required, and this demands dedicated staff, who have to be paid. There can be little doubt that adherence to a carefully-prepared set of antibiotic guidelines can be cost-effective [2, 3], but obtaining the initial injection of money into a guideline programme usually requires independent funding, commonly from government sources, as academic institutions or hospitals rarely have spare resources to divert in this direction. This is one project that is unlikely to be funded by the manufacturers of antibiotics, and in any case antibiotic policies should be seen to be independent and not compromized in any way. Another method of reducing expenditure on antibiotics may be by providing information about drug costs when issuing the results of antibiotic sensitivities [4], although it is not clear what effect this strategy has on the quality of treatment.
A. J. Smith et al.: Antibiotics policies In addition to a thorough discussion of these problems during the conference, five treatment areas were examined in some detail in order to establish whether or not consensus was remotely possible. For simple urinary tract infections it appeared that the quinolones were fast winning the day in India, although not necessarily appropriately. The adoption of the World Health Organization classification of acute respiratory infection emerged as a logical basis for deciding on the need for antibiotics, particularly as sputum culture cannot be relied upon to give clear microbiological guidance. Fever of short duration, commonly diagnosed in India, withered as a category, and no-one doubted the need for accurate diagnosis and the best microbiological evidence before embarking on antibiotic treatment in all but desperate cases. However, it was noted that in general practice antibiotics are extensively misused in such cases. The role of prophylactic antibiotics in surgical wound infection, an area in which good evidence is available from randomized controlled clinical trials, was debated in some depth. Last to be discussed was pyogenic meningitis, a common illness in India and one in which antibiotic sensitivities of causative organism have changed over the past few years. The availability of many drugs over the counter without prescription and an inadequate emphasis on patient education were recognized as major factors militating against the better use of antibiotics. The influence of advertizing was also highlighted in a presentation which contrasted the information provided by pharmaceutical companies for prescribers of the same drugs in Western countries and in India. Almost uniformly, the advertized indications for antibiotics were wider in India, while notes on contra-indications and adverse effects were much more detailed in information provided to Western prescribers. Clearly in some cases there are double standards. Although the conference focussed on antibiotics it was forcefully reminded that the management and prevention of infections must be seen in a wider context. Adequate water supplies, health education, and improvements in hygiene might make a greater impact on the prevalence of some infections than any antibiotic policy. As we left the conference hall and the campus of the Christian Medical College Hospital it was difficult not to notice the roadside stalls which are so much a feature of Indian life. Many purvey antibiotics - of varying quality, one suspects - in single or multiple doses. If introducing and giving effect to antibiotic policies is difficult in the developed countries of the world, how much more difficult is it in developing countries, where so many economic and commercial counter-pressures co-exist and where regulation is so much less effetive. One thing is certain. Clinical pharmacoligists cannot stand aloof from legitimate concerns about the worldwide use and abuse of anti-infective drugs. If we do, we will be justly criticised for being perfectly prepared to devote the resources of our laboratories and units to the investigation of 'me-too' compounds, while being unwilling to be involved in the urgent task of examining drug use in the real world and adding our weight to those trying to improve things.
A. J. Smith et al.: Antibiotics policies
References 1. Levy SB, Burke JR Wallace CK (eds) (1987) Antibiotic use and antibiotic resistance worldwide: report of a study sponsored by the Fogarty Internationel Center of the National Institutes of Health, 1983-86. Rev Inf Dis 9: Suppl 3 2. Friesen WT, Hekster CA, van der Kleijn E (1981) Drug utilization studies in a hospital: the interpretation of record-linked data and the effect of therapeutic audit on drug usage. Aust J Hosp Pharm 11:40-46 3. Landgren FT, Harvey KJ, Mashford ML, Moulds RFW, Guthrie B, Hemming M (1988) Changing antibiotic prescribing by educational marketing. Med J Aust 149:595-599
87 4. Rubinstein E, Barzilai A, Segev S, Samra Y, Modan M, Dickerman O, Haklai C (1988) Antibiotic cost reduction by providing cost information. Eur J Clin Pharmacol 35:269-272
Dr. J. K. Aronson MRC Clinical Pharmacology Unit Radcliffe Infirmary Woodstock Road Oxford OX2 6HE, UK
