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  • Antibiotic resistance and the developing world

Many factors are increasing antibiotic resistance, and authorities, doctors and patients all have a role in fighting it, writes Jia Hepeng.

Developing countries, struggling under the burden of bacterial diseases such as tuberculosis, are more in need of antibiotics than ever. But issues such as proliferation of counterfeit drugs, poor prescribing practices and a lack of regulation or guidelines are fuelling the growth of resistance to these much needed medicines.

Antibiotic resistance is when an antibiotic has lost its ability to effectively control or kill bacterial growth. The bacteria targeted adapt by natural selection to become 'resistant' and continue to multiply despite the presence of the antibiotic.

This is not new. Ever since the drugs were first discovered in the mid-twentieth century, bacteria have evolved to evade them. But although the problem of resistance is global, in developing countries even common bacterial infections are showing resistance, warns Shrikant Bhatt, professor of medicine at the University of Nairobi, Kenya.

Xiao Yonghong, deputy director of the Institute of Clinical Pharmacology at Peking University in Beijing, China, is part of a national working group that has been monitoring bacterial drug resistance for several years. In China, he says, resistant bacteria cause about 60–70 per cent of infections from common bacteria — such as Escherichia coli that causes intestinal infection and Pneumococcus that causes pneumonia.

In countries with poor healthcare services and where people cannot necessarily afford hospital care, the growing inability of doctors to treat common infections has serious implications for public health.

Inadequate diagnostics

The most direct contributor to resistance is the overuse of antibiotics, says Xiao. He estimates that 30 per cent of drugs sold in Chinese hospitals are antibiotics, while in the developed world the proportion is only ten per cent.

Gao Zhancheng of the Department of Respiratory and Critical Care Medicine at Peking University's People's Hospital agrees. When a disease cannot be controlled initially, he says, the most common solution practised by many Chinese doctors is to frequently change the patient's prescribed antibiotics.

The problem stems partly from the poor diagnostic capability of most the country's clinical laboratories, says Gao. "Doctors often use broad-spectrum antibiotics because they cannot clearly identify the specific pathogens that cause the diseases."

When a disease cannot be controlled, Chinese doctors frequently change the patient's antibiotics

Flickr/interplast

In India, laboratory facilities often simply don't exist, or operate with extremely poor standards. Most of these laboratories are poorly funded and ill-equipped to conduct the standard tests required to reliably identify the bacteria causing the disease, yet alone whether the bacteria is resistant to particular drugs.

 "They mostly use homemade antibiotic disks which are not standardised," says Pradeep Seth, a former professor at the department of microbiology at the All India Institute of Medical Sciences in New Delhi.

"Inevitably, these methods often lead to inconsistent and unreliable results….Thus, with no means of determining which antibiotic to prescribe, doctors must rely on clinical judgement alone."

Equipment and technology upgrades do not necessarily solve the problem either. With diseases that need urgent treatment, such as pneumonia, doctors cannot afford to wait for pathological laboratory results, and need to use their clinical judgment and experience.

Gao says that because information on recent disease-causing strains is often non-existent, doctors are severely constrained in their ability to choose a specific antibiotic. 

Poor prescribing practices

When antibiotics are not used correctly, they fail to completely kill off the disease-causing bacteria in a patient. The lingering remnants of the bacteria are this allowed to develop resistance.

Many countries have no national policies on use of antibiotics, leading to irrational and unnecessary use of antibiotics. "It is intriguing that none of the government-run hospitals in [India] have any antibiotic policy worth its name. Very few private hospitals have a working antibiotic policy," says Seth.

This results in inappropriate prescribing practices, including the wrong choice of antibiotics with incorrect dosage and duration of treatment.

Weak government guidance on prescribing practices has major consequences.

In Kenya, Bhatt says, "doctors are too quick to prescribe the latest drugs in the market" instead of saving them for use when existing drugs are ineffectual.

The problem comes when there is combined pressure from two sides: patients who insist on leaving the clinic with a prescription for antibiotics, and healthcare workers willing to prescribe them without a thorough medical investigation or a clear diagnosis.

Kenya's nurses are not supposed to prescribe antibiotics but, says Bhatt, they sometimes do so under pressure from patients who go direct to the nurses' houses.

The fact that patients are willing to take prescriptions from healthcare workers who do not have the authority is due to the 'white coat' effect, says Bhatt. "Anybody in a white coat who works at medical institution is considered a doctor. This can do a lot of damage."

In addition, he says, many doctors and pharmacists are "too busy" to specify the dose the patient should take, a situation that is aggravated in rural areas where people share doses prescribed for one patient.

"Even the most educated people need to be told the dangers of not completing doses," he says, adding that a lot of people also discontinue their course of drugs when they start to feel better.

Zhan Shaokang, a public health expert from the Shanghai-based Fudan University, says that in China, many patients treated for TB stop taking their drugs once the symptoms disappear. Such irregular usage of drugs is likely to lead to resistance, he warns.

Chinese doctors are also facing an additional dilemma. Government subsidies to hospitals only account for ten per cent of their revenues, and drug sales provide half a hospital's income. The financial benefits from prescribing antibiotics present hospital doctors with a clear conflict of interest.

Take tuberculosis (TB) treatment, for example. The disease is common among migrant populations in China and the government offers free TB drugs to rural and urban poor patients. However, research by Zhan shows that that many doctors insist on prescribing medicines to protect the liver from the side effects of TB antibiotics, even though the WHO does not recommend them.

The drugs prescribed are often expensive, he says. This dissuades many of the poorer patients from seeking TB treatment at hospitals.

Poorer patients cannot afford the often-expensive drugs prescribed

Credit: Flickr/sparktography

With China's pharmaceutical industry booming, increased production and the accompanying economies of scale mean that it is cheaper for drug companies to produce antibiotics. The higher profit margin this allows for means that pharmaceutical firms are pushing more antibiotics into hospitals, says Xiao.

China's Ministry of Health has issued guidelines for the prudent use of antibiotics in hospitals. But Xiao says if the hospitals' reliance on drug sales cannot be changed, the measures will not offset the economic needs of hospitals to prescribe more antibiotics.

In recent years, calls to reform China's profit-oriented medical system have been growing and the authorities have commissioned several large-scale research studies on the future reform of medical systems. Although nothing has yet been put into action, healthcare workers and public health advisors widely believe that hospitals' reliance on drug sales can be changed.

According to Xiao, one option is for medical insurance companies — who pay for patient's prescriptions — to refuse to reimburse unnecessary prescriptions. Local medical associations, rather than unified central authorities, should be involved in drafting more specific guidelines that take into account which bacterial strains are most common locally, as well as information on local patients' situations.

Unregulated drug sales

But patients are also able to obtain drugs without a prescription from a doctor.

In developing countries, there are various reasons why people resort to buying medicines not prescribed by a doctor. Factors include not being able to afford the prescribed drugs, a lack of awareness of what causes antibiotic resistance, and poor access to regulated pharmacies or hospitals.

Mo Xiaochuan, a doctor from the Beijing-based China-Japan Friendship Hospital, says many patients ask for as large a supply of antibiotics as possible to avoid having to revisit the hospital for a repeat prescription.

Some migrant workers working in cities stock-up on antibiotics to avoid hospitalisation. "For migrant workers who are not covered by medical insurance and labour protection, hospitalisation and leaving work to visit doctors could lead to them losing their jobs," says Zhan.

Guo Jinhua, a retired worker in the northern Chinese city of Datong, says she prefers to go to drug stores rather than hospitals to obtain antibiotics. "Hospitals sell the drugs more expensively and we have to wait in the long line," she complains.

In 2003, the State Food and Drug Agency banned pharmacies from selling antibiotics without doctors' prescriptions. But many have found a way around that. They hire retired doctors to write prescriptions for customers, despite often having no equipment to conduct proper testing.

Many patients are seeking alternative methods of obtaining drugs, such as drug stores and street vendors

Credit: Flickr/ ThisParticularGreg

In Kenya, Bhatt says there are a rising number of street vendors or unlicensed sellers who sell antibiotics as if they were food supplements.

Unregulated pharmacies often dispense drugs with no prescription, says Willis Akhwale, head of the Division for Malaria Control at the Ministry of Health in Kenya. He says that although the artemisinin-based therapy for malaria is a prescription-only drug, people still manage to obtain the drugs over the counter at pharmacies.

Brazil's government is also struggling to maintain control over antibiotics sales. Unlike in developed countries, where pharmacies retain all prescriptions they dispense, Brazilian pharmacies are only required to hold on to prescriptions for drugs with 'black-labelled' warnings — those that can cause serious side-effects, such as antidepressants. The pharmacies must report the sale of such drugs to governmental surveillance agencies.

Antibiotics, however, do not come under this classification, and their sales go unrecorded. According to Anvisa, the government National Health Surveillance Agency responsible for regulating medicine sales in Brazil, there is a bill pending to ensure that these prescriptions are retained by pharmacies, but this has not been passed.

"When this law passes we will be able to control medicine sales better," says Leandro Queiroz Santi, manager for the investigation and prevention of infections and adverse effects at Anvisa.

Any unprescribed use of antibiotics contributes to overuse of the drug, but the real worry is counterfeit drugs. Some are diluted versions of the real thing, which risk fuelling resistance even further — the active agent present in too low an amount to kill the bacteria, allowing resistance to develop.

There is a growing market for cheap generic drugs, mostly from Asia and South-East Asia. Some come from reputed companies that meet the drug manufacturing standards of the WHO and the US Centers for Disease Control and Prevention. But, says Bhatt, the market is flooded with counterfeits, with no regulation of the industry in sight.

In February 2007, India's Associated Chambers of Commerce and Industry of India (ASSOCHAM), an industry body, released a survey estimating that the country's counterfeit drug industry was growing by 25 per cent each year, with sales exceeding US$3.95 billion annually.

Fake versions of common antibiotics such as amoxicillin, and erythromycin, and doxycycline — as well as common painkillers such as paracetamol — are widely sold over the counter, raking in huge profits for their manufacturers.

And counterfeit drugs are beginning to be sold by manufacturers to pharmacies in New Delhi's government hospitals. The ASSOCHAM survey estimated that 10–15 per cent of medicines sold in the hospitals were fake. Drug regulation authorities say the labels on the fakes are so authentic that it is difficult to make out the spurious from the genuine. The authorities are also too under-staffed and ill equipped to test samples regularly on a large scale.

Growing reform

Moves to reform existing practices and develop guidelines are underway, although these have been slow to take effect. 

Since the late 1990s, China has established national research working groups to monitor antibiotic resistance periodically.

The WHO will provide more guidance on antibiotic use for doctors

Credit: Flickr/harlemdakota

Hans Troedsson, the WHO's China representative, says the organisation is aware of the danger of antibiotic resistance in the developing world, and has been working with governments like that of China to design a comprehensive plan to control it.

This includes designing a mechanism to control the unnecessary hospital prescription of antibiotics, and updated training with the latest antibiotic resistance knowledge for both students and working doctors. The WHO is also looking to provide more guidelines on antibiotic use to the Chinese Ministry of Health.

In Brazil, Anvisa, together with the Pan American Health Organization (PAHO), has begun a project called Rede RM (Network of Microbial Resistance Monitoring and Control) in an attempt to identify levels of antibiotic resistance in the country. According to Anvisa, a government media campaign warning about the dangers of using of medications without prescription is scheduled to launch this May.

All the experts SciDev.Net spoke to emphasise the importance of raising awareness of the problem of antibiotic resistance both in the medical community and amongst patients.

Jaldo de Souza Santos, president of the Brazilian Federal Council of Pharmacy, which oversees the country's pharmacies, says patients need to be aware of the consequences of using antibiotics incorrectly and know to only buy them with a medical prescription and directly from a pharmacist.

Changing the way the general public thinks about antibiotics is crucial, says Mo Xiaochuan. "A common cold does not need antibiotics, but many patients think of antibiotics as a panacea, so they hope to store as much of them at home as possible."

Additional reporting by Cassius Guimarães, Ochieng' Ogodo and T. V. Padma.

This article is part of a Spotlight on Fighting antibiotic resistance.

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