* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Inappropriate Antibiotic Use in the Philippines
Survey
Document related concepts
Transcript
Inappropriate Antibiotic Use in the Philippines Emmanuel Edwin R. Dy, M.D.* (*Senior Research Specialist II, Philippine-Australia Cooperation Project on National Drug Policy) Inappropriate antibiotic use refers to improper administration with respect to drug dose, interval duration (whether singly or collectively) in the light of proper clinical situations and/or financial considerations. The recognized effects of inappropriate use (whether overuse or underuse) of antibiotics are multiple: (1) rapid emergence of resistance, (2) selection pressure on resistant microorganisms, (3) adverse reactions, (4) treatment failures, (5) occurrence of preventable morbidity and mortality and (6) waste of resources. This is a review of local and foreign/published and unpublished literature from 1985 to 1995 with the objective of gathering data explaining the multidimensional problem of local inappropriate antimicrobial use and attendant development of resistance. Inappropriate use comes as a result of a miltiplicity of factors. The community/consumer is influenced/characterized by misconceptions, financial constraints. The behavior is reinforced by pharmacists’/drug sellers’ practice of conducting transactions without prescription. The physician's behavior is greatly influenced by lack of access to unbiased drug information and standard national treatment guidelines. High drug prices (an offshoot largely of promotions and/or a result of preset profit margins) and lack of emphasis on cost and adverse effects of promoted antibiotics are the identified contributions of the drug industry to the problem. The use of antibiotics in agriculture and aquaculture is still another contributory issue: presence of antibiotic residues in products from these industries, which do not disappear with freezing or cooking prior to human consumption. Since routine local antimicrobial resistance surveillance commenced in 1988, there has been an upward trend in resistance rates for most microorganisms. Nosocomial infections have been increasing in number in tertiary medical centers in Metro Manila. Tuberculosis has assumed another dimension in its continued domination as one of the leading causes of morbidity and mortality with the identification of multiple drug resistance. This is often a result of poor patient compliance and/or physician adherence to recommended treatment guidelines. This paper was developed as part of a multisectoral process which is working towards a coordinated strategy to improve use of antibiotics. (Phil J Microbiol Infect Dis 1997; 26(2):77-87) Key Words: antibiotic, inappropriate use Inappropriate antibiotic use refers to improper administration with respect to drug, dose, interval, duration (whether singly or collectively) in the light of proper clinical situations and/or financial considerations. It is a wide spread phenomenon that has been written about in foreign literature. Largely a result of a complex interplay of several factors, it often arises from failure to define accurately the objectives for which the agent is given or from lack of knowledge of the properties of the drug. 56 Antibiotics are generally beneficial in treating susceptible bacterial infections but such beneficial effects are counter balanced by rampant irrational use.52 The prime consequence of misuse is the rapid emergence of antimicrobial resistance48,73,76 and its attendant disease aftermath. 48 Irrational use leads to selection pressure on resistant microorganisms and subsequent spread of resistance genes, and preventable morbidity and mortality arising from treatment failures. Adverse reactions are an unwanted feature of all drugs. Some practitioners would consider underdosaging because of fears of a reaction. But scientific investigations have clearly shown that when an antibiotic regimen is inadequate, therapy is ineffective, resistant strains emerge, superinfections ensue and therefore both efforts and resources are wasted2 and ultimately the total cost of therapy increases.7 Modern medical microbiology has established that the dominant factor in the selection of bacteria with either intrinsic or acquired resistance in the hospital and in the community is the extensive use of antibiotics.7,48 Multiple resistance (where bacteria are resistant to several antibiotics) can be transferred from one species to another.7 Misuse is found in both developing and developed nations but the problem is more acute in the former because of limited finances. Some nations have limited the extent of misuse through implementation of regulations coupled with education. Resistance to antibacterial agents is more prevalent in some parts of the world than in others.52 There tends to be higher levels of resistance in Shigella, penicillinase producing Neisseria gonorrhoeae, and M. tuberculosis in developing countries. Moreover in developing countries with few laboratories to detect resistant strains on first appearance or no new agents to treat infections caused by these strains, greater prevalence of such strains can be expected.52 Also, resistant bacteria frequently cause nosocomial infections.37 What is the local antibiotic scenario? Antibiotics account for 15 - 30% of drug expenditures, the largest of any therapeutic group of drugs.15,41,79 A study by the World Health Organization's Programme for Appropriate Health Care Technology (ATH) has shown a correlation between the occurrence of multiresistant bacteria and antibiotic consumption patterns.7 The Philippines has the highest percentage in 1983 of antibiotic utilization among countries (including USA, Japan, United Kingdom) surveyed (>25%).15 In a more recent survey (1990), the Philippine figures did change significantly. However, majority of the people whether rich or poor allot minimum expenses for medical care at 2.7% and 1.2%, respectively. 72 Yet the local market is flooded with volumes of medications.8 Are the overwhelming drug consumption figures reflective of an "artificially created market and not the actual medical need? 60 Or, are there significant nonhuman sources of antibiotic use? There is as much underuse as there is overuse.15 Lansang et al44 revealed that community purchases were made without prescriptions in 66.3% of 1608 transactions. There was a low median number of dispensed medications citing financial constraints as the more common reason for noncompliance with the prescribed regimen. More important than this reason is the lack of patient awareness that the regimen should be completed as exemplified by the common practice of discontinuing the treatment once symptoms subside and as typified by anti-tuberculosis treatment practices. Information on antibiotic use on a national level has always been found to be scanty, and hospital consumption contributes little in total drug use in much of the developing world. 16 At best, conclusions can be inferred only from data/trends noted in tertiary training hospitals in Metro Manila. An illustrative case is the problem of antibiotic utilization in acute diarrheal diseases in children. The oral rehydration therapy (ORT) has been actively promoted since 1980 by the DOH as the cornerstone of therapy and that antibiotics have a limited role since only 10% of cases are caused by dysentery. In 5 different provinces since 1987, there has been a consistent and progressive increase in the use of antibiotics and antidiarrheals. This was explained by caretakers' practice of self-medication and consultation with private practitioners who favor antidiarrheal and antibiotic therapy over rehydration therapy. 8 At set indicator levels for the use of intravenous rehydration, antibiotics and other drugs, there was note of disparity between standard treatment guidelines and actual practices. A 15-year review of infections at the Philippine General Hospital (PGH) from 1971-1987 showed that gram-negative bacteria constituted the most commonly isolated organisms 76 with an average of 37-63 percent of antibiotic resistance In 1994, these findings were consistent with foreign literature. Costs of antimicrobial utilization of the different departments in the same institution from January to March 1994 revealed that surgery (P381.740.94), obstetrics and gynecology (P506,996.13), medicine (P677,054.65) and pediatrics (P337,910.21) had 32.35%, 16.21%, 10.07% and 6.25% respective of their budgets allocated for restricted to very restricted antibiotics respectively. In a retrospective analysis of 1,578 antimicrobial prescriptions at the institution's emergency room complex in 1989, prescribed antibiotics were considered inappropriate in 65.2% of cases and 61% were given prophylactically. Respiratory tract infections comprised the most common condition noted. Unemployed patients made up 42% of the population studied. 77 The value was similar to the figure of 64% for inappropriate prescription cited by the Health and Public Policy Committee of the American College of Physicians.7 At the Clinical Division of the Santo Tomas University Hospital, Villar et al79 studied the antimicrobial utilization pattern from 1990 to 1991. Fifty-eight percent of the patients received antibiotics singly or in combination. There was no clear indication for the antibiotic in 4 percent; 42% of patients received the antibiotic for therapy and 54% received the antibiotic for surgical chemoprophylaxis. Based on accepted standards for antimicrobial usage, there was inappropriate use of antibiotics in at least 35% of cases. The greatest identified problem was in surgical chemoprophylaxis with respect to the indication, timing, duration and choice of antimicrobials. Antimicrobial utilization trends at St Luke's Medical Center showed that 45.7% of therapeutic regimens and 89.4% of prophylactic regimens were considered inappropriate.21 Is the problem recognized locally? The problem of inappropriate antibiotic use is not the physician's alone - it is shared by the other health professionals drug sellers/pharmacists, barangay health workers, government, community and the pharmaceutical companies as well. Local literature documents some revealing practices which should be taken into consideration in attempting to curb the problem. The Community Understanding behavioral patterns related to antibiotic use in the community should go beyond the routine KAP surveys. Antibiotics use is influenced at least in part, by cultural preferences and beliefs about medications.41 Common misconceptions include: (1) for every symptom, there is a specific remedy; (2) antibiotics as wonder drugs; (3) the more expensive a drug is the more likely it is to be effective; (4) injections as more "powerful" forms of medicines; and (5) drug use should be stopped when symptoms subside. Patients/caretakers (like some physicians) generally consider antibiotics to be relatively risk-free and are often not troubled by considerations of under treatment or development of resistant organisms.6 Some generalities about behavioral patterns related to antibiotic use include: (1) knowledge is not necessarily about antibiotics, e.g. "gamot sa ubo" or "gamot sa sipon" (medication for cough or medication for colds); (2) antibiotics are used for infections but notion of the latter is usually vague leading to the belief that infection is synonymous with fever; (3) "strong" antibiotics are considered "bad"; (4) antibiotic dosage is directly related to severity of disease (e.g. rifampicin at 450 mg is for "weak lungs" while 600 mg of the same drug is for tuberculosis). Widespread self-treatment often with the least effective agent in an incorrect dosage, is considered a major factor in the development of bacterial resistance in developing countries.7 Locally, Hardon29 noted the practice of recycling prescriptions for recurrence of symptoms initially assessed by a doctor. Self-medication is a prevalent practice influenced by the cost of consultation and/or the confidence in the prescription habits of the doctor.29,41,43 This is substantiated by the observation that ampicillin was the most common antibiotic prescribed by the physicians and used as self-medication. 29 Recycling of prescriptions is further explained by the usual concept of "hiyang" i.e. a drug is perceived as useful for a particula r patient’s illness leading to its repeated use.71 An example of this is caretaker's perception and management of diarrheal disease which may result from milk formula that is not "hiyang" or from something "marumi" (dirty).71 Correspondingly, caretakers resort to changing the milk formula or (worse) using anti-infective treatment depending on which concept appealed/applied at that particular instance. Sia et al63 furthered Hardon's findings with the following data: (1) antibiotics comprised 21.6 percent of stored household drugs, (2) stored medications averaged 3.6 per household, (3) 60.7 percent of population adopted the practice and (4) reasons for storage included first aid measures and left-overs. Commercial sex workers share beliefs and practices according to experiences and pieces of advice passed on from group to group. Symptomatic and/or prophylactic antibiotic use is/are tailored to type of customer, presence of symptoms and effectiveness of previous prescriptions. The notion that antibiotics are much easier (and more accessible) to use aggravates the problem of widespread drug resistance in sexually-transmitted diseases. The Pharmacist/Drug Sellers The person behind-the-counter, whether the pharmacist or the drug seller, also has a large contribution to the pervasive practice of self-medication. Lansang et al noted that written prescriptions were available in only 57 percent of 6404 drug transactions in a rural pharmacy and that median number of antibiotic units dispensed on a single visit was 6 capsules/tablets or 1.5 vials/ampules.43 Financial constraints, the cultural concept of "hiyang", discontinuation of antibiotic upon relief of symptoms and the allocation for other forms of treatment are factors curtailing the patient's ability to purchase the full course. Worse, pharmacists/drug sellers may also act as "pill consultants" for walk-in patients who are just "shopping" for affordable medications or may substitute/choose another medication (non-generic equivalent) in lieu of the prescription; such practices definitely make antibiotics (and other drugs for that matter) far too accessible. Analyzing further the situation, the bottom line is that the physicians are unable to enlighten the patient about repercussions of poor compliance and self-medication with antibiotics. There is also need for better communication between physician and pharmacist. The pharmacist/drug seller is also an essential client of the medical representative. The medical representative monitors the physician's prescriptions by doing weekly checks on the local pharmacy for his monthly report. The ability to gain access to such data and the unspoken potential of the drug seller's clout in pushing his product to walk-in customers depend on the rapport between medical representative and dispenser which is generally furthered by giving them samples, gimmicks and deals.75 Realizing the strong influence of the person behind-the-counter and still using the diarrhea situation as the example, a survey was recently conducted by the National Control of Diarrheal Diseases Program of the Maternal and Child Health Services regarding knowledge, attitudes and practices of Manila pharmacists on diarrhea treatment.51 It showed that the respondents had ample knowledge of the disease. However, inadequate advice, recommendation of mild substitutes and antidiarrheal agents and less utilization of oral rehydration solution (ORS) were commonly noted. ORS was perceived as a drug to stop diarrhea and not as fluid and electrolyte replacement. Findings generated from the study shall be utilized to correct the situation of continued antidiarrheal/antibiotic use and lack of emphasis on ORS. The Prescriber The physician often has to contend with self-medication practices of patients which may mask underlying infection. 41 With this reality, he often resorts to newer broad spectrum agents.55 The practicing physician has the medical representative and the Philippine Index of Medical Specialties (PIMS)60,61 as his ready references for acquainting with new drugs. This is also compounded by the lack of standard national guidelines (or the lack of dissemination thereof) and the inability to individually address efficacy. Limited surveys on doctors' prescribing habits show that pharmaceutical products are being prescribed inappropriately. 60 Doctors-in-training prescribed more rationally than practicing ones; prescribed antibiotics less frequently when confronted with diarrhea, fever or sore throat cases; and favored non-drug therapy over drugs.60,61 Polypharmacy or multiple drug utilization is a common practice, i.e. a therapy for every (potential) symptom. 16,30,32,44 Hardon29,30 particularly noted that there was a higher average number of medications per illness case in doctors' prescription than in self- medication. Physic ians also utilized antibiotics as diagnostic tools in severe cough and diarrhea cases to determine whether the cause is bacterial or not.29-30 The dentist similarly prescribes antibiotics but there are no local studies on his prescribing habits available. Dental infections are commonly caused by Streptococcus, Peptostreptococcus, Peptococcus, Fusobacterium, Bacteroides and Actinomyces sp. Antibiotics widely accepted for dental indications are the penicillins, cephalosporins amino-glycosides, and erythromyc in.54 Of these, penicillin remains the drug of choice because of efficacy, low cost and ease of administration. 54-67 Aside from the undocumented contribution to irrational antimicrobial prescription, antimicrobial resistance is linked to mercury resistance (from amalgam fillings) because of common genetic locus(i). Mercury released from amalgam can cause an enrichment of mercury resistance plasmids in normal bacterial flora.67 The Drug Industry In 1993, the total pharmaceutical market in the Philippines was valued at P23.8B ($930M), up by 5.8% over the previous year58 despite increased regulatory controls. Close to 80% (P18.9B) of total sales were through drugstores the volume of which has improved by 5% with prescription products accounting for P13B. In line with previous years, almost all therapeutic products were branded and the Metro Manila area accounted for nearly 45% of nationwide drugstore sales. Systemic anti-infectives continued to lead the pack accounting for 22.2% of the total value of drugstore sales at P4.187M. An intriguing observation is the fact that retail drug prices are highest in the Philippines compared with other Southeast Asian countries (Table I).20,30,62 In fact, medications exported to other countries (e.g. Hongkong and Singapore) are cheaper than the locally marketed counterparts. Medicines continue to be expensive and are often inaccessible for common illnesses.72 Tan noted that the Generics Act of 1989 which should have helped people make cost-saving choices, has been poorly implemented. This resulted from: (1) physicians disregard for generic prescribing, (2) few generic products carried in drugstores, and (3) effects of continued advertising on people.72 Retail pharmacies have a limited mark-up so the high costs can well be attributed to production, distribution and marketing expenses. Largely responsible for the success of the industry are extensive promotions and fostering of close personal relationships with physicians, built on a number of core Filipino cultural values like "utang na loob" (debt of gratitude).23 Direct face-to-face presentation by medical representatives continue to be particularly effective thus the industry's vast expenditure. Medical representatives, among other tools of the drug companies are often the first source of information about new drugs and are influential in physician's decisions to prescribe a drug for the first time.1,81 As detailers of drug information, medical representatives are grossly ill equipped. Thus, physicians rarely ask them additional information about their products.23,48 The PIMS which is frequently utilized similarly as source of drug information, is practically a product of the industry. 32,60,61 Locally, 68% of the average promotional budget is spent on representatives salaries and travel expenses23,53 while the remainder covers literature and documentation (14%), samples (9%) and scientific seminars (9%). Promotions are not limited to company-labeled items but may even extend to provision of personal physician amenities/necessities as anonymously disclosed by medical representatives when enjoined to participate in a research conducted by van Staa.75 Studies have shown that such behavior is common among local practitioners.1,14,68 A number of studies have identified the "missing essentials" in the industry's thrust: (1) rare mention of costs6,23/side-effects6,80 and (2) educational value.80 These are considered essentials because nondisclosure of the good and bad effects of the drugs may spell harm for the end-user (i.e. the patient) whose outcome is decided for by the physician. 18,23,80 In an era where several similar drugs are often available for a given condition, it is more important that physicians be provided with accurate information. 80 Table 1. Retail drug prices of 100 unit s (tables/capsules) of 24 commonly used drugs in 29 countries all values are given in US dollars at the current exchange rate. Two economic indicators and retail prices of four food items are given. 70 DEVELOPING COUNTRIES IN THE ASIA PACIFIC REGION Bangla deesh Minimum daily wage USD Real GOP per capita (PPP$)1991 Name Strength of Drug in mg Amoxycillm 250 Atmoxil 250 Capoten 25 Cimetidtne 200 Tagamet 200 Cotnmoxazole 480 Septrin 480 Diazeparn 10 Valium 10 Diclofenac 50 Voltaren 50 Erythromvcin 250 Erythrocin 250 Furosemide 40 Lasix 40 Adalat 5 Adalat 10 Propranolol 40 Inderal 40 Inderal 80 Ranitidine 150 Zantac 150 Common Food item Rice Sugar Milk Eggs Average 1 kg 1 kg 1L 1 dozen HK 150 India Indo nesia Malay sia 1.6 Nepal Pakis tan Philip pines 1.7 2 5.6 Sri Lanka Thai land 5.6 1160 18,520 1,510 2,181 7400 1130 1970 2.440 2.650 5,270 6-9 4-6 03 02 10 01 20 33 01 05 33 47 73 12 42 26 31 23 31 47 119 09 10 05 03 03 03 03 02 02 12 11 2 3 04 8 03 03 10 40 06 56 07 25 48 52 10 37 02 33 18 04 74 150 16 34 54 20 35 08 16 03 16 29 08 12 06 22 25 41 05 12 86 08 09 05 03 03 03 02 02 03 03 05 oe 21 09 14 03 05 03 07 16 05 07 0.6 02 01 28 14 39 22 29 54 95 20 53 46 52 25 37 20 35 40 12 25 95 04 24 25 02 23 01 09 0.14 03 02 29 05 09 0.6 05 09 0.6 05 63 05-24 17-26 33 03-12 34 04 8-14 08 04 40 6-16 20 9-14 20-26 04 13 26 20-40 74-132 0.4 6 0.79 0.62 0.89 1.44 0.97 1.37 0.67 0.47 0.47 0.50 0.47 0.40 0.72 0.36 1.34 0.56 0.52 1.00 0.76 0.32 0.44 0.28 0.75 0.52 0.50 0.39 0.65 0.40 0.68 1.63 1.02 0.39 -0.62 0.50 055 1.00 1.25 0.69 1.11 0.48 0.71 071 0.45 052 0.93 0.83 Source: Personal Communication from HAI partners in the respective countries. PPP$ UNDP, Human Development Report, 1194 New York, Oxford University Measures such as curbing drug advertisements,17,20 occasional DOH warnings 19 and issuing ethical guidelines1,49 have been put in place but the sales figures cited earlier certainly belie the effectiveness of such tools. Appropriate intervention should be directed at helping the physician understand the complexities of the drug industry, aside from knowing the drugs utilized in his practice.79 There are no means to check on the claims of drug ads, leading to proliferation of drug advertisements with unfounded claims.20 In response to this paper, the Pharmaceutical Health Care Association of the Philippines (PHAP) and the Philippine College of Pharmaceutical Medicine (PCPM) issued a position paper57 acknowledging occurrence of antibiotic resistance caused by a multiplicity of factors - over-thecounter (OTC) sales, self-medication, poor patient compliance, poor quality of products (e.g. DOH rifampicin) and empiricism due to unavailability of laboratory facilities. The paper also highlighted self-regulating mechanisms by the industry. It also contained the commitment of the industry to cooperate with the DOH in solving the problem of inappropriate antibiotic use. The paper also strongly suggested that critical appraisal of literature using only well-controlled and large studies can help avoid making generalizations about drugs. The Use of Antibiotics in Agriculture and Aquaculture Animal feed additives have for many years constituted the largest and most controversial category of antimicrobial use.26 Col and O'Connor 35 noted that non-human uses accounted for a significant share of the market in developing countries and confirmed that data on production and trade generally do not distinguish between human and non-human uses or between therapeutic and non-therapeutic uses. In a largely agricultural country like the Philippines, antibiotics are utilized extensively in animal feed production. Such may partly explain why the antimicrobial consumption is disproportionate to the purchasing power of the average Filipino. Commonly utilized and advertised antibiotics include cotrimoxazole and cotrimazine. Chloramphenicol, at one time, was utilized in aquaculture. The primary concerns addressed have been the generation of antibiotic resistance in animal bacteria and the influence of such resistance on human health. 82 The presence of antibiotic residues in meat, milk and their products poses potential human health hazards since cooking and freezing have minimal effects on residues.7 Experience in Germany showed a distinct reduction in selection pressure and decrease in oxytetracycline resistance among Enterobacteriaceae after reduction in 1981 and final prohibition in 1983 were enforced as a government strategy. 74 New resistance genes and multiresistant organisms with increased pathogenicity are emerging in animals as a direct consequence of antibiotic exposure.82 Cabrera in a local experiment elucidated the role played by the popular practice of supplementing animal feeds with antibiotics in the spread of multiple resistance among microorganisms through either selection of resistant strains or through genetic recombination via conjugation. She demonstrated transfer of chicken multi-drug resistant Escherichia coli plasmids to human antibiotic sensitive E. coli. Is antimicrobial resistance a problem in the Philippines? That misuse results into resistance requires proof of presence of the latter locally. In a 6year surveillance (from 1988 to 1994) of mostly Metro Manila institutions 12,13 there has been noted an increasing resistance for Salmonella typhi against ampicillin, chloramphenicol and cotrimoxazole; shigellae against cotrimoxazole; Pseudomonas aeruginosa against ceftazidime and fluoroquinolones; Escherichia coli against gentamicin and cotrimoxazole. In general, Enterobacteriaceae has increasing aminoglycoside resistance (Figures 1 - 5) while Neisseria gonorrheae now has established fluoroquinolone and beginning ceftriaxone resistance. Unfortunately, there have been no concurrent antimicrobial consumption pattern studies to help establish a link between misuse and resistance. Multi-drug resistant tuberculosis is one nagging problem that has been acknowledged as a result of poor adherence to prescribed drug regimen. The surveillance done in selected areas provide valuable information on resistance pattern. Recognizing the problem, Mendoza et al50 investigated the nature and predictors of multi-drug resistant tuberculosis (MDT-TB) at the PGH from June 1992 to May 1995. Of 299 subjects, 165 (55%) had cavitary chest radiographs, 245 (82%) had acid-fast bacilli in sputa and 167 (56%) had anti-TB treatment previously. Among these parameters, previous anti-TB treatment was the sole predictor of MDR-TB. Table 2 shows the overall drug susceptibility pattern. What can be done about the situation? The problem of misuse is difficult to solve single -handedly and success may be difficult to achie ve. The multifaceted problem deserves a complex multisectoral solution. In the current set-up, physicians are hardly reminded about the repercussions of antimicrobial misuse. The drug industry is implementing self-policing measures but the situation is still far from ideal. Meanwhile, there are still little efforts to educate and/or investigate the Filipino patients self- medicating practice. While a minority of physicians is inclined towards conservatism, the majority and their patients still adhere to the belief that "without a prescription, a doctor is no good." Figure 2. Yearly resistance rates of shigellae all institutions, Sept. 1988-Dec. 1994. Resistance rates are not within acceptable range and should be continuously surveyed with possible inclusion of more institutions nationwide. Projections for developing countries in the next 10 years regarding established antimicrobial utilization and consumption indicate no change in trend. 52 This calls for a more urgent stand and the urgency stems from the need to prevent the potential aftermath of spread of resistant micro-organisms. The output of the surveillance program should be disseminated to as many institutions nationwide as possible. To be able to arrive to this end, a certain level of awareness should be raised starting with solicitation of active support from government and non-government organizations (NGOs). The surveillance program has been without funds until 1994 and the present funding is from research projects which shall end on June 1997. The situation still allows some leverage for policymakers to resolve the problem by adopting a multisectoral approach. Rational drug intervention programs must be primarily directed at students while they are in the medical school. They should be reinforced during their training years in the hospital, and while in active medical practice. Educational efforts should also be targeted at the dispenser the barangay health worker, the aquaculture/agriculture sector because they are also recognized stakeholders in the problem. The absence of role models should be realized and addressed for the stakeholders to emulate. Local medical journals should also take the step in checking the claims of advertisements and should consider non-pharmaceutical but doctor-related products as part of their advertising clientele to support their viability. Table 2. Overall drug susceptibility pattern of multidrug resistant tuberculosis at the Philippine General Hospital (1992 - 1995)50 N = 299 Sensitive to 5 drugs (RHESZ) Total drug resistance Rifampicin (R) Isoniazld (H) Ethambutol (E) Streptomycin (S) Pyrazinamide (Z) Multidrug resistant HR Not HR Total Number 50 249 Single Drug Resistance (SDR) 2(0.7) 7 (2.3) 77 (25.8) 1 (0.3) 2 (0.7) Percent 16.7 83.3 Total (MDR and R) 102 (34) 135 (45) 210 (70) 66 (22) 51 (17) 95 (38) 65 (26) 160(64) SUMMARY 1. Clinically and economically inappropriate use of antibiotics is a major problem in the Philippines and internationally as well. There is both overuse and underuse. The problem is more acute in developing countries because of limited resources. 2. The consequences of antibiotic misuse include increased selection pressure of resistant microorganisms, preventable morbidity and mortality from treatment failures, adverse drug reactions and wastage of limited health care resources. 3. The problem of inappropriate use of antib iotics is complex, multi-factorial and involves numerous stakeholders. 4. There is no simple solution but the first step is to get all stakeholders to acknowledge that a major problem exists and that cooperation is essential if national and global solutions are to be achieved. RECOMMENDATIONS An urgent campaign should be developed to address the issue of antibiotic misuse and the emergence of antimicrobial resistance. All stakeholders need to be involved in the development and implementation of the educational strategy to address the problem. REFERENCES 1. Alora AT. Ethical pharmaceutical promotion. Santo Tomas J Med 1994; 43(3):105-108. 2. Alora AT, Estrada DR, Judan EA. Untoward reactions to antimicrobials. Phil J Microbiol Infect Dis 1986; 15(2):57-62. 3. Antimicrobial resistance surveillance in Metro Manila. Drug Monitor 1990;5(6):?4-76. 4. Antibiotic resistance and dispensing regulations. Drug Monitor 1987; 2(3):15-16. 5. Aswapokee N, Vaithayapichet S, Komoltri C. The failure of a preprinted order form to alter physicians antimicrobial prescribing pattern. J Med Assoc Thai 1992; 75(4):223-230. 6. Avorn J, Harvey K et al. Information and education as determinants of antibiotic use: report of task force 5. RID 9 (suppl 3):S286-296. 7. Benetley A. The antibiotic crisis. In problem drugs. Amsterdam Health Action International 1993; 51-68. 8. Bravo LC, Santos-Ocampo PD. Drug use in acute diarrheal diseases in children: the Philippine experience. Workshop on Rational Drug Use and CDD, Lung Center of the Philippines, 24 February 1992. 9. Bucci KK, Frey KA. Involvement of pharmacy faculty in the development of policies for pharmaceutical sales representatives. J Fam Pract 1992; 34(l):49-51. 10. Cabrera E. Drug susceptibility patterns of conjugal transferability of multiple drug resistance in E. coli isolated from the intestinal tracts of chicken receiving antibiotic supplemental feeds from poultry/farm workers. DLSU/PCHRD. 1991. 11. Cadle RM, Darouiche RO, et al. Pharmacist's impact on antimicrobial drug therapy. Am J Health Syst Pharm 1995; 52:15441546. 12. Carlos CC. The 1994 antimicrobial resistance surveillance data (in press). 13. Carlos CC. The antimicrobial resistance surveillance program progress report (Jan – Dec 1993). Phil J Microbiol Infect Dis 1994; 23(1):50-51. 14. Chren MM, Laudefeld S, Murray TH. Doctors, drug companies and gifts. JAMA 1989; 262(24):3448-3451. 15. Col NF, O'Connor RW. Estimating worldwide current antibiotic usage: report of task force 1. RID May - June 1987; 9(suppl 3): S232-S243. 16. Colley CA, Lucas LM. Polypharmacy: the cure becomes the disease. J Gen Intern Med 1993; 8(5):278-283. 17. Congress to pursue curbs on ad spending. Drug Monitor 1989; 4(11):146-147. 18. Danguilan MJ. Drug commercials scored (letter). Drug Monitor Nov 1988; 8(11):129-130. 19. DOH rationalizes approach to infectious and tropical diseases (warns on use of antibiotics and antimicrobials). Drug Monitor Aug 1990; 5(S):103-104. 20. DOH proposes regulating of drug ads. Drug Monitor Aug 1987; 2(8):3-5. 21. Dumo CC, Natino DFG, Pena AC, et al. Antimicrobial utilization in a tertiary hospital (abstract). 17th Annual Convention. Philippine Society for Microbiology and Infectious Diseases. November 1995. 22. Echols RM, Kowalsky SF. The use of an antibiotic order form for antibiotic utilization review: influence in physicians prescribing patterns. J Infect Dis 1984; 150(6):803-807. 23. Evans RG. Manufacturing consensus marketing truth: guidelines for economic evaluation. Ann Intern Med 1995; 123(1):59-60. 24. Fletcher RH, Fletcher SW. Pharmaceutical advertisements in medical journals. Ann Intern Med 1992; 16(11):951-952. 25. Griffin JP, Griffin TD. The economic implications of therapeutic conservatism. J Royal Coll Phys London 1993; 27(2):121-126. 26. Gustafson RH. Use of antibiotics in livestock and human health concerns. J Dairy Science 1991; 74(4):1428-1432. 27. HAI calls for stronger regulation of over-the-counter drug advertising. Drug Monitor Sept –Oct 1994;9(5):l-3. 28. HAIN Databank. The drug industry in the Philippines: 1986. Drug Monitor Jul 1987; 2(7):2-3. 29. Hardon AP. Confronting ill health; medicines self-care and the poor in Manila. HAIN Manila 1991; 173-187. 30. Hardon AP. The use of modern pharmaceuticals in a Filipino village: doctors prescription and self-medication. Soc Sci Med 1987; 25(3);277-292, 31. Hartigan-Go KY. Adverse drug reaction monitoring: experiences in the Philippine General Hospital. Acta Med Philip 1992; 164-166. 32. Hartigan-Go KY, Yu H. Drug interaction consciousness in the Department of Medicine Philippine General Hospital with emphasis on the use of a computer-assisted system for monitoring and reporting adverse drug interactions. Acta Med Philip 1992; 170-177. 33. Hoppe SA, Gora-Harper ML. Influence of pharmaceutical sales representatives on the formulary sylem. Am J Health Syst Pharm 1995; 52:1549-1551. 34. Hossain MM, Glass Rl, Khan MR. Antibiotic use in a rural community in Bangladesh. Int J Epidemiol 1982; 11 (4):402-405. 35. Infection Control Committee, Philippine General Hospital 1985 -1987. 36. Infection control committee and infectious diseases section, Philippine General Hosp ital 1994. 37. Javato-Laxer M, Navarre E, Littaua R, et al. Antimicrobial prescribing patterns in hospital: determinants and proposed interventions. Phil J Microbiol Infect Dis 1989; 18(2):41-46. 38. Karlowsky J, Ferguson J, Xhand G. A review of commonly prescribed oral antibiotics in general dentistry. J Can Dent Assoc 1993; 59(3):292-294. 39. Kessler DA. Addressing the problem of misleading advertising (ed.). Ann Intern Med 1992; 116(10):950-951. 40. King A, Coley KM. Evaluating the accuracy of citations in drug promotional brochures. Ann Pharrnacother 1994; 28(11):12311235. 41. Kunin CM, Upton HL, Tupasi TE, et al. Social behavioral and practical factors affecting antibiotic use worldwide; report of task force 4. RID May -June 1987; 9(suppl 3):S270-285. 42. Kunin CM, Chambers S. Responsibility of the infectious disease community for optimal use of antibiotics: views of the membership of the IDSA. RID Jul - Aug 1985; 7(4):547-559. 43. Lansang MA, Juban N, Macachor L, Kunin CM. A drugstore survey of antibiotic use in a rural community in the Philippines. Phil J Microbiol Infect Dis 1991; 20(2):54-58. 44. Lansang MA, Lucas-Aquino R, Tupasi TE, Kunin CM, et al. Purchase of antibiotics without prescription in Manila the Philippin es: inappropriate choices and doses. J Clin Epidemiol 1990; 43(l):61-67. 45. Lexchin J. Interactions between physicians and the pharmaceutical industry: what does the literature say? Can Med Assoc J 1993; 149(1):1404-1407. 46. Lexchin J. Agents against pediatric diarrhea: assessing the information companies supply to Canadian physicians. Can Fam Phys 1994; 40:2082-2087. 47. Levy R. The role and value of pharmaceutical marketing. Arch Fam Med 1994; 3(4):327-332. 48. Liss RH, Batchelor FR. Economic evaluations of antibiotic use and resistance – a perspective: report of task force 6. RID MayJune 1987; 9(suppl 3):S297-S312. 49. Margolis LH. The ethics of accepting gifts from pharmaceutical companies. Pediatrics 1991;88(6):1233-1237. 50. Mendoza MT. University of the Philippines College of Medicine Tuberculosis Study Group. Nature of drug resistance and predictors of multiple drug resistant tuberculosis among patients seen at the Philippine General Hospital, Manila Philippines. 1995 (in press). 51. National Control of Diarrheal Diseases Program, Maternal and Child Health Services. Survey of pharmacists/staff knowledge and practice regarding diarrhea treatment in Manila. Department of Health 1995. 52. O'Brien TF, et al. Resistance of bacteria to antibacterial agents: report of task force 2. RID May-Jun 1987; 9(suppl3):5244-5260. 53. Opposition to limits on advertising. Drug Monitor Jul 1989; 4(7):92-93. 54. Owens BM, Schuman NJ. Antibiotics and dentistry: a brief review. J Clin Fed Dent 1994; 18(2):129-134. 55. Pallares R, Dick R. Wenzel JP, et al. Trends in antimicrobial utilization at a tertiary teaching hospital during a 15-year period (1978-1992). Infect Control Hosp Epidemiol 1993; 14(7):376-382. 56. Parker MT. Antibiotic resistance in pathogenic bacteria. WHO Chronicle 1982; 32(5);191-196. 57. Pharmaceutical Health Care Association of the Philippines and Philippine College of Pharmaceutical Medicine. Position paper on rational use of antibiotics (1995). 58. Philippine Pharmaceutical Market - 1993. Drug Monitor Sept- Oct 1994; 9(5):1. 59. Preus HR, Albandar JM, Gjermo P. Antibiotic prescribing patterns among Norwegian dentists. Scand J Dent Res 1992; 100(4):232 - 235. 60. Quijano RF. Prescribing habit s and attitudes of medical practitioners in the Philippines. Drug Monitor Mar-Apr 1992; 7{2):1527. 61. Quijano RF, Sia IC, Senturias EN. A descriptive study of the prescribing habits of three groups of physicians in Manila. Acta Med Philipp 1989; 25(3):S8 -92. 62. Retail drug prices of 100 units of 22 commonly used drugs in 29 countries (personal communication). HAIN, 1994. 63. Sia IC, Velayo LG, Mateo, et al. Parmakolohiya sa komunidad; mga nakatagong gamot sa mga bahay sa Barangay Bungo, Gapan, Nueva Ecija. Acta Med Philipp 1993; 161-166. 64. Simon HJ, Folb PI, Rocha H. Policies, laws and regulations pertaining to antibiotics: report of task force 3. RID May-Jun 1987; 9(suppl3):S261-269. 65. Spiro HM. Prescription persuasion. Drug Therapy 1992; 112-114. 66. Stratton CW, Ratner A, Johnston PE, Schaffner W. Focused microbiologic surveillance by specific hospital unit: practical application and clinical utility. Clin Ther 1993; 15(suppl A):S12S20. 67. Summers AO, Wireman J, Vimy MJ, et al. Mercury released from dental "silver" fillings provoked an increase in mercury and oral antibiotic-resistant bacteria in oral and intestinal floras of primates. Antimicrob Agent Chemother 1993; 37(4):825-834. 68. Tan ML. Drug needs and utilization patterns in 4 urban poor communities of Metro Manila. Drug Monitor April 1988; 3(4):2349. 69. Tan ML The pharmaceutical industry in 1990. Drug Monitor Nov - Dec 1991; 6{11/12):96-104. 70. Tan ML Large drug firms continue to control local market. Drug Monitor 1986; 1(6):1-2. 71. Tan ML. Some sociocultural determinants of drug use. Workshop on rational drug use and CDD, Lung Center of the Philippines, 24 February 1992. 72. Tan ML. Philippine Health Matters 1995. Health Alert (special issue); 11 (182):9, 38-39. 73. Thomas J HI. National survey of hospital policies on pharmaceutical sales representatives activities. Am J Hosp Pharm 1987; 44:1334-1340. 74. Trolldenier H. Witte W, Briedigkeit H. Decreasing oxytetracycline resistance in enterobacteriaceae in veterinary and health conditions after exchange of this substance in animal nutrition. Zentralblatt furllyg Umeveltmed 1991; 192(3):264-278. 75. Van Staa AL. Drug promotion - a mutual bond: pharmaceutical representatives and do ctors in the Philippines. Drug Monitor 1994; 17:22-23. 76. Velmonte MA. Surveillance of antibiotic susceptibility at the Philippine General Hospital. Acta Medica Phil 1985; 21(4):126131. 77. Velmonte MA, Ong G, Marasigan LC. A profile of antimicrobial prescribing in the University of the Philippines - Philippine General Hospital emergency room complex (Nov 7 – Dec 7, 1989). Fil Fam Physician 1990; 28:1 -18. 78. Velmonte MA. Surveillance of antibiotic susceptibility at the Philippine General Hospital. Acta Med Philipp 1985; 21(4):126131. 79. Villar EP, Co NM, Co BG et al. Antimicrobial utilization in a tertiary teaching/training hospital. Santo Tomas J Med 1994; 43(l):44-57. 80. Wilkes MS, Doblin BH, Shapiro MF. Pharmaceutical advertisements in leading medical journals: experts assessments. Ann Intern Med 1992; 116(11):912-919. 81. Yang YH, Fu SG, Peng H, et al. Abuse of antibiotics in China and its potential interference in determining the etiology of bacterial pediatric diseases. Pediatr Infect Dis 1993; 12(12}:986-988. 82. Young HK. Do non-clinical uses of antibiotics make a difference? Infect Control Hosp Epidemiol July 1994; 15(7):484-487. 83. Zellmer WA. Rethinking hospital pharmaceutical marketing. Am J Health Syst Pharm 1995; 52:1590.