A costly misuse

India is one of the countries where the third and fourth lines of antibiotics are being used indiscriminately, research has suggested, even as the world recently celebrated 'Antibiotics Awareness Week'.

A paper authored by three researchers of Gurugram-based Public Health Foundation of India (PHFI) has said antibiotics were being prescribed for treating upper respiratory infections (URI) the most among all diseases.

Ironically though, most URIs are self-limiting and do not require treatment with antibiotics at all, according to standard treatment guidelines.

The paper, "Outpatient prescription rate and pattern in the private sector in India: Evidence from medical audit data" was recently published in the journal PLOS ONE.

"Our estimates suggest a high proportion of antibiotic prescription for upper respiratory tract infections namely acute upper respiratory infections (20.4 per cent), cough (4.7 per cent), acute nasopharyngitis (4.6 per cent) and acute pharyngitis (3.9 per cent)," the paper said.

"Generally, these infections are viral in origin and are self-limiting in nature. A significant proportion of these antibiotic prescriptions might be inappropriate in nature," it added.

Viral infections, in fact, can't be treated by antibiotic drugs at all. Why then are antibiotics being prescribed the most against URIs?

"These are common illnesses and keep occurring. Also, people often have a tendency to rush to big hospitals even for common cold. These hospitals would anyway prescribe mostly costly drugs," said Sakthivel Selvaraj, one of the authors of the paper.

"Worse still, the third line of antibiotics is to be prescribed only at hospital-level, usually in ICUs and only if the severity of the infection has reached that stage. However, to our utter surprise, we found that they are being prescribed at the primary care level. This is totally unscientific and unacceptable," he added.

Costlier antibiotics abused more

The prescription rate of antibiotics in India is 412 prescriptions per 1,000 persons per year, the researchers noted in the paper. Around 519 million antibiotic prescriptions were dispensed in India in 2014.

The researchers claim theirs is the first paper to come up with the antibiotic prescription rate in India.

India's rate isn't much when compared to European countries like Italy (957 prescriptions per 1,000 persons), Germany (561 prescriptions per 1,000 persons), UK (555 prescriptions per 1,000 persons), Denmark (481 prescriptions per 1,000 persons) and Greece (1,100 antibiotics per 1000 person).

The catch, however, lies in the fact that when it comes to the antibiotic drugs which are a third and fourth line, India beats a number of countries. The percentage of prescriptions with cephalosporins and quinolones (38.2 per cent and 16.3 per cent) in India were significantly higher than the United States (14.0 per cent and 12.7 per cent), and Greece (32.9 per cent and 0.5 per cent).

"Such unusually high prescription rates of beta-lactams — penicillins and cephalosporins — in uncomplicated upper respiratory infections in children is in stark contrast to the prescription rates and pattern reported in European countries," the paper reads.

The antibiotic prescription rates were the highest for children aged 0-4 years and the lowest in the age group 10-19 years.

And what are those drugs which are being prescribed the most? Across all age groups, beta-lactam cephalosporins had the highest prescription rate, followed by beta-lactam penicillins and quinolones. Cephalosporins were the most commonly prescribed antibiotic across all diagnoses with the exception of disorders of the urinary system where quinolones were more commonly prescribed. While upper respiratory infections took the pie, many others contributed to antibiotic abuse.

How does this affect patients?

Most of these third-generation antibiotics are costlier than their first and second-generation counterparts. The paper does not say to what extent the cost of the treatment gets escalated due to antibiotic abuse. "We believe the cost increases by roughly 20-25 times," Selvaraj said. In fact, one of the primary drivers for these drugs being prescribed was the high profit that pharma companies made by selling them, he said. "The pharma companies are heavily pushing them in the market with aggressive advertisements through medical representatives who have to lure doctors with various offers," Selvaraj said.

The researchers also wrote that in the private sector, not only were the antibiotic prescription rates higher but the choice of antibiotics for the treatment of uncomplicated respiratory infections was also inappropriate. Moreover, people in India spend the most on medicines. The latest National Sample Survey Organisation (NSSO) report has said the maximum expenditure among the five major components of healthcare expenses — doctor's fee, medicines, diagnostic tests, bed charges and others — was incurred on medicines.

More investment in costlier antibiotics

Heavy profiteering in higher grade antibiotics is pushing the pharma sector to invest more in them at the cost of lower grade ones. A 2013 study from New Delhi exposed a sub-optimal availability of some 'access' group antibiotics, such as benzathine penicillin and amoxicillin, while other 'watch' and 'reserve' group antibiotics, such as fluoroquinolones and carbapenems, were freely available.

Leena Menghaney, a lawyer with the Access Campaign at the international humanitarian medical organisation Médecins Sans Frontières/Doctors Without Borders wrote a piece for DTE in which she said lower margins in the 'access' group of antibiotics and heavy profiteering in the 'watch' and 'reserve' group was pushing the pharma industry to shun the former and embrace the latter. The 'access' group are first-line antibiotics while 'watch' and 'reserve' are higher ones.

The growing burden of AMR

The worst effect of antibiotic abuse, however, is the growing burden of antimicrobial resistance (AMR), with more and more bacteria becoming resistant to the drugs. India, incidentally, has the highest burden of AMR. "In this context, this paper should set alarm bells ringing for policymakers. It is high time these findings are taken seriously. To the best of our knowledge, our study provides the first-ever estimates of outpatient antibiotic prescription rates and patterns in the private sector," Selvaraj said.

India is already a hub of infectious diseases. According to the Million Death Study implemented by the Registrar General of India, infectious diseases such as pneumonia and diarrhoea accounted for around 50 per cent of deaths in children aged less than 5 years in India.

The latest NSSO report also said that it is the infections, among all causal factors, which are making Indians sick the most.

AMR, in itself, is just not a medical problem but it escalates the cost of treatment too. Quoting this study, the researchers say due to growing AMR, antibiotic costs, pharmacy costs and the overall cost of treatment were much more in people resistant to drugs rather than those who responded to them.

"Health consequences such as intensive care admissions, complications, mortality and length of stay were significantly higher in the resistant group as compared to the susceptible group," the study said.

Huge lacunae in the implementation of guidelines

"The literature suggests that perceived demand and expectations from the patients, influence from medical representatives and inadequate knowledge influences doctors' decisions to prescribe antibiotics," the PHFI paper reads, enumerating some of the factors.

The over-the-counter sale of antibiotics is further adding to the menace. "The non-prescription sale of carbapenems in India is the highest in the world and contributes to growing carbapenem resistance," the paper reads. Numerous studies have reported increasing levels of resistance to last-resort antibiotics like carbapenem. "Besides, the prescribers just don't follow guideline which is unscientific. I mean, what makes them prescribe antibiotics for the common cold?" asked Selvaraj. But why it is so? "The 'standard treatment guidelines' in India are not mandatory. And. The private sector is almost unregulated. It does not leave any stone unturned to maximise profits," he said.

"The fact that in European countries, you find prescription rates of antibiotics to be much lower is because there, the treatment guidelines exist not just on paper but are implemented in letter and spirit," he added.

Views expressed are strictly personal