Misuse and overuse of antibiotics: Who is to blame?

The misuse and overuse of antibiotics has given rise to the serious problem of antimicrobial resistance worldwide. While doctors and, to a much lesser extent, patients must take the blame, it is principally a problem caused by the ruthless drive of drug companies in their quest for super profits.

by Ong Beng Gaik

A MALAYSIAN executive in his mid-thirties developed a stomach upset and diarrhoea after a meal. He consulted his company doctor. He left the clinic with six little white packets - two types of antibiotics, two types of painkillers (Ponstan and Panadol), a small white pill for diarrhoea, and a pink tablet to be chewed three times a day. He was flabbergasted. 'I thought I only needed something to control the diarrhoea until I got home.'

This case could be repeated in many clinics anywhere, reflecting the inappropriate and excessive use of antibiotics. For instance, a 1992 study (a joint effort by the National University Malaysia and the Health Ministry) conducted at six government hospitals reveals that Malaysians are taking far more antibiotics than they need to. Why? It showed that there had been abuse of antibiotics in treating patients because doctors were prescribing them excessively. Similarly, a recent study of an emergency room in a private hospital in Manila showed that over 90% of patients who received antibiotics did not really need them.

Misuse also arises because the drug is so easily available outside the doctor's clinic, especially in developing countries. Given the lax restrictions and enforcement there, antibiotics are sold in black markets and in pharmacies over the counter to people who can afford them and use them as they please by under- or overdosing themselves. For example, one study in Nigeria found that all of the members of the public surveyed and 73% of university students interviewed admitted to having used antibiotics at least once for a variety of symptoms before consulting a doctor.

Indiscriminate use of the drug has undermined its effectiveness - giving rise to drug resistance in disease-causing bacteria everywhere. As it has become a global phenomenon, accompanied by virulent outbreaks of diseases and infections, World Health Organisation (WHO) has called for urgent action worldwide to fight the spread of such drug-resistant diseases. In collaboration with other organisations in the US, it has recently created WHONET - a surveillance system of bacterial resistance at local, national and global levels involving 150 labs in 30 countries.

Also, the World Medical Association has felt the need to propose resolutions regarding this 'public health problem of potentially crisis proportions' at its 48th WMA General Assembly in October this year in South Africa.

So who bears the blame: the doctor for prescribing the drug for a common flu or as prophylaxis, or the patient who expects and demands the pill for every ill - or worse, who even self-medicates? Or the pharmaceutical industry for promoting it as a cure-all since the Second World War?

Healthy business

We would do well to remember that, according to a drug company spokesman, people who run drug companies are not bishops, they are businessmen.' (Cured to Death by Arabella Melville and Colin Johnson).

When a successful formulation of a medication comes into the market, other companies usually try to cash in on it by producing a 'me-too' product to have a market share. That is why in India alone the drug market has 70,000 preparations compared to WHO's list of 250 essential drugs.

This phenomenon is also shown clearly in the case of antibiotics. In the WHO Essential Drug List, there are only 20 antibiotics but there are over 200 antibiotic preparations sold in Malaysia, for example. This baffling array can only generate confusion among prescribers.

But the profits are nothing to be sneezed at. The global market for these drugs alone was worth US$22 billion in 1993. By 2000, the market is expected to reach US$40 billion. In Malaysia, 1993 imports of antibiotics (including those in veterinary products) cost over RM85 million up 100% since 1982 - with penicillins taking up 28% of the total. These drugs made up 14% of all medicinal and pharmaceutical products for both humans and animal use.

And now that antibiotic resistance is prevalent round the world, it simply means - because the first antibiotic prescribed often fails - the patient has to be put on several others or even hospitalised in grave cases. This adds about US$100 to US$200 million to health-care costs in the US alone where the total US antibiotics market costs about US$6 billion a year.

And the more the phenomenon of resistance spreads, the more pharmaceutical companies have to invest in new antibiotic research - money that they can recoup with the charging of very high prices for the latest drugs. The latest drugs can cost over US$500 a day for treatment! Can a developing country afford the extra costs for the newer medication even if they're available?

Drug companies are out to run a good business, and to be popular with shareholders and governments. According to a report by the WHO, 'there is an inherent conflict of interest between the legitimate business goals of manufacturers and the social, medical and economic needs of providers and the public to select and use drugs in the most rational way.'

The drug industry - health or profit motive?

Part of the antibiotic misuse is fostered by the drug companies which zealously promote the medicine as a cure-all in order to sell as much as possible against rival products. Because there are so many drugs sold that are similar, the competition among companies to push their own brands is fierce. What results is uncontrolled drug promotion, leading to a pill-for-every-ill syndrome and the irrational use of drugs.

Another strategy is to try to widen the indications for its products, that is, claims are made beyond what the drugs can do - even false, misleading or unsubstantiated claims,especially in developing countries.

Manufacturers justify their excessive promotion and unethical marketing practices by arguing that they are only following the regulations of these countries. For example, many more precautions are listed for antibiotics sold in the US than in less developed countries.

Also, the trend is all too familiar in many countries, especially the industrialised ones: Mass marketing, to recoup the costs of developing the new products, leads to them becoming a fad, popular with patients and physicians in the know. Old, cheap faithfuls such as penicillins, tetracyclines, and sulphonamides are discounted in place of more expensive and more heavily promoted ones like quinolones, cephalosporins, and macrolides, though impartial sources always recommend doctors to stick to well-proven and established narrow-spectrum drugs and keep the newer broad-spectrum ones for those fewer patients who have drug-resistant infections or are allergic to standard ones.

Is it any wonder then that doctors have been known to turn to these companies, following the lead of their medical representatives in the "best" or latest drugs to use? And these pharmaceutical companies, having spent hundreds of millions of dollars' worth of advertising, are obviously biased when it comes to pushing their brands over their rivals'.

Their prime motive - to make more profits and grow - has seen to a global marketplace cluttered with an increasing number of products that are inappropriate, irrational, needlessly expensive, or even useless. Their commercial interests, usually outweighing that of public interest, can lead them to some dubious business practices outlined below:

Marketing ploys

Marketing itself is a big business with pharmaceutical companies. In the US, it is a billion-dollar industry. The conflict between public interest and marketing becomes apparent once a drug becomes available on the market. The company wants returns on the product as quickly as possible given the stiff competition, with the company spending at least 20% of sales on pushing its products - twice more than on research and development. The question we should ask is how far should these companies go in encouraging the use of their drugs?

Usually the drug maker is forced into heavy promotion to recoup research and development costs within only six or seven years after a new drug is introduced. In Australia, drug companies spend A$200 million every year just to market their products. The sum represents almost A$10,000 a year spent on attempting to win each of Australia's 21,000 GPs. This is 50 % more than allowed by law in the UK for marketing.

In Japan, there are an estimated 43,000 drug salesmen and almost as many wholesaler representatives. An average Japanese doctor receives 450 sales calls a year.

In Britain the pharmaceutical industry also realises the importance of bringing new products to the attention of GPs. As a result, about two million visits are paid by sales representatives, with the average GP receiving some 62 visits a year.

In developing countries, doctors find it hard to resist the hard-sell tactics of multinationals. According to Dr Mediadora Saniel of the Research Institute for Tropical Medicine near Manila, the promotion for medicine, especially antibiotics, is heaviest in developing countries like the Philippines (New Straits Times (Malaysia), 6 February 1996):

'No one is spared from medical representatives. They will give free samples, and many will invite doctors to social occasions, to dinner. They'll even take care of spending for trips abroad, for medical conferences.' A typical sales pitch, said Dr Saniel, would involve a seminar in a posh hotel in which a Western doctor would lecture on a new drug's benefits. Even if the local doctors are not completely convinced by the drug's effiicacy, they would feel grateful for the first-class treatment.

How receptive are the doctors to the sales pitch to use the higher priced new medicines? Take quinolones, among the latest antibiotics to be developed in the 1980s. Yet they already accounted for 15% of the world's antibiotic market in 1990.

Americans spend US$700,000 a day on just one type, ciprofloxacin. in 1989 it was the fourth most commonly prescribed antibiotic in the US - with over 5 million prescriptions at a cost of US$248 million. Yet according to clinicians in the US, much of the expenditure is inappropriate. Would sales have been so high had it not been for heavy promotion? In the first half of 1988, ciprofloxacin was the second most advertised product.

A study (reported in the International Herald Tribune, 3 June 1992) by the University of California revealed that ads in medical journals are misleading about the safety and effectiveness of new drugs. Their benefits are often exaggerated or unbalanced. And especially in developing countries, these claims in the promotional literature and ads are not regulated and certainly not in the interest of public health. Yet these ads and literature are the prime source of information for doctors. For example, Malaysian doctors tend to use either handouts they get from medical representatives or the Drug Index for Malaysia and Singapore (DIMS), published by the drug companies themselves. According to the study, misinformation could lead to the prescribing of inappropriate drugs. Drug companies have also found an effective way to use the credibility of medical journals for their own purposes by sponsoring or subsidising the publication of supplements.

Take the case of ciprofloxacin. In the US the largest consumer-governed health maintenance organisation (HMO) placed this quinolone antibiotic on its formulary with specific use criteria. They were concerned that intense promotion of this drug could lead doctors to believe it would be suitable for most infections.

The Malaysian ad found in DIMS only bolsters this misleading image: 'Unknown pathogens, mixed infections, problem organisms...', 'High-performance quinolone for bacterial infection'. The list of indications that follow reads like a who's who of infections: all, naturally, could be eradicated by this new cure-all called ciprofloxacin.

Nowhere did the ad point out that this antibiotic, among the newest to be developed, is inappropriate for unrestricted use as a first-line drug. The connection between promotion and inappropriate prescription is clear.

A WHO expert committee has suggested that a reserve list of fewer antibiotics like the third-generation cephalosporins, quinolones and vancomycin be set aside for specific indications such as infections caused by organisms resistant to standard drugs and not be available for unrestricted use.

Sharing profits with hospitals

Drug companies can also work with the complicity of hospitals in a variety of kick-back schemes. For example, the spread of MRSA (methicillin-resistant S. aureus) in Japan is directly linked to the longstanding dependence of hospitals there on income from drug prescriptions.

Japanese doctors allegedly prescribe three times more antibiotics per patient than their Western counterparts. Not only that, the drugs they use tend to be the expensive, broad-spectrum types like second- and third-generation cephalosporins, which carry a higher profit margin than oral penicillins. The drug companies encourage this practice - as it means more profits for them too.

The reason it worked so well was due to the medical fee system, in which prescriptions were covered by the public health insurance fund. Doctors were paid an official price for drugs regardless of their real cost. At the same time, to encourage doctors to dispense their products, the drug companies offered doctors generous discounts of up to 24% of the drug official prices. Doctors or hospitals could thus pocket the difference. The more drugs a doctor or hospital sells, the higher the profit margin.

Also profit margins for expensive drugs like cephalosporins make up a large part of a hospital's income. The value of this discount scheme is estimated at £7 billion each year. In 1988 Japan's market for injectable antibiotics amounted to about £1.7 billion; cephalosporins accounted for 71% of the total, compared to about 24-55 % in the US and Europe.

Thus it is not surprising that these overprescribed cephalosporins, on the market since the last decade, have now no effect on the MRSA despite their broad antimicrobial spectrum. In a move to shake up this scheme between drug companies and hospitals, the Health Ministry took the step to bar drug manufacturers from directly fixing prices with health institutions, giving wholesalers the right instead.

Irrational products

The 'me-too' practice has also given rise to a multitude of irrational products. The most common is the combination products, for example, a sulpha drug plus an antibiotic or an antihistamine plus an antibiotic or two antibiotics for which the company's patents have run out. They are formulated and marketed under a new brand name and their superiority over other brands is extolled in expensive campaigns.

One example is the combination product containing antibiotics to fight diarrhoea. (A dangerous and useless practice, since experts point out that most diarrhoea is caused by viruses which are unaffected by antibiotics.)

Yet nearly two out of every three antidiarrhoeal preparations sold in 12 countries in Latin America in 1990 contained an antibiotic. Similarly, a survey carried out in 1989 showed that nearly one out of two antidiarrhoeal products in Third World countries contained an unnecessary antibiotic.

Dumping of banned products

Some companies, the less scrupulous ones, can go further in unethical practices. A common practice is the export of their banned or restricted products to poorer countries where regulations and restrictions are more lax, where doctors have no information (like pharmacopoeia) to rely on but company handouts and publications, and where the company has a large, hardworking team of sales representatives to boost sales.

According to the Working Group on Health and Development (WEMOS) in Amsterdam, 75 products (including some antibiotics) which had been pulled out or banned in one or more European countries were identified in the Third World in 1991. Perhaps it's accepted business practice that life is cheaper there.

Compared to people in developed countries, there is as yet little awareness among the people of the Third World of the link between antibiotic misuse and resulting drug resistance in disease germs. However, educating the public isn't enough. The root of the problem lies in the powerful institutions, like the drug companies, which are pushing the sale and use of these drugs, and in the over-dispensing clinics and hospitals.

What's needed are stricter policies to deal with the problem of overprescription, inappropriate and uncontrolled use of the drug. For instance, standardised labelling could be the first step, as advocated by the International Association of Pharmaceutical Companies: the dangers of inappropriate use, potential and types of side-effects, and full contraindi- cations should be printed on every drug label - as a standard in all countries, regardless of local regulations.

At the same time, governments and medical bodies should devise means and programmes to monitor, evaluate, control, and prevent hospital-based infections, while providing training and consultation for medical personnel on the appropriate and safe use of antibiotics. As antibiotic resistance knows no national boundaries, they should link up and cooperate with their counterparts, agencies and NGOs at home and abroad mutual in surveillance, research and training.

Ong Beng Gaik is a Publications Officer attached to the Consumers Association of Penang.