India is witnessing an alarming rise in antibiotic resistance, much of which has been triggered by overprescription of the drugs by doctors, overuse by patients and unregulated use on farms and fisheries. But another factor contributing to this rise in antibiotic resistance is the unavailability of simple antibiotics that should be used as the first line of treatment.

The lack of such first line antibiotics has resulted in people across India using stronger drugs to treat simple infections. Pathogens, therefore, develop resistance to these stronger drugs faster and render even the more basic antibiotics ineffective.

On June 6, the World Health Organisation updated its Essential Medicines List, revising the antibiotic section extensively. Keeping in mind extensive and growing antibiotic resistance across the world, the WHO grouped antibiotics into three categories – access, watch and reserve with recommendations on when each drug can be used.

The “access” category has 29 first-generation antibiotics that should be widely available and affordable, states the WHO document. The “watch” group of antibiotics can be the first and second choice for treatment of a small set of infections but whose use should be reduced as much as possible to prevent resistance. “Reserve” antibiotics are last resort medicines to be only in the most severe circumstances when all other alternatives have failed.

In India, many of the “access” group antibiotics are only sparsely available.

“Antibiotics such as benzathine penicillin, ampicillin and nitrofurantoin are not available in the country,” said Dr Sumanth Gandhra from Centre for Disease Dynamics, Economics and Policy, a public health research organisation with its headquarters in Washington DC. “At least not as much as they are supposed to be.”

Gandhra, who works at the centre’s Delhi office, was an advisor to the WHO committee that updated the Essential Medicines List.

Benzathine penicillin injections are commonly used for treating syphilis and rheumatic heart disease in children. Ampicillin is used to treat a variety of bacterial infections and nitrofurantoin is used to treat urinary tract infections.

Many of these “access” category antibiotics are narrow spectrum drugs that target certain kinds of bacteria and do not attack the beneficial bacteria that are generally found in the human body. Stronger antibiotics are broad spectrum drugs that are more effective. But continued and widespread use of these stronger antibiotic makes pathogens resistant to them faster and also resistant to the less potent, basic drugs. The basic drugs then fail to kill the new drug-resistant pathogens. Therefore, the availability of “access” category drugs is important to control the spread of antibiotic resistance.

At the same time, there are a few cases in which drugs that had been rendered ineffective decades ago due to resistance seem to be working in the Indian population again. In the 1980s, there were many cases of multi-drug resistant typhoid, which led to the reduced use of ampicillin that was used to treat the disease. Now, samples of the Salmonella typhi bacteria are showing sensitivity to ampicillin again.

Color-enhanced scanning electron micrograph showing Salmonella Typhimurium (red) invading cultured human cells. (Image: Rocky Mountain Laboratories, NIAID, NIH/Wikimedia Commons)
Color-enhanced scanning electron micrograph showing Salmonella Typhimurium (red) invading cultured human cells. (Image: Rocky Mountain Laboratories, NIAID, NIH/Wikimedia Commons)

Dr Yogesh Jain, one of the founders of the Jan Swasthya Sahyog and who runs the community hospital in Bilaspur, Chattisgarh, said only certain pharmaceutical distributors stock first line antibiotics and other essential medicines.

“Sometimes these drugs are more often available in Chhattisgarh than in Delhi,” said Jain.

First line antibiotics are also more easily available in government run facilities than in private pharmacies, clinics and hospitals. This is because these drugs are part of the National Essential Medicines List that is used to procure medicines in the public sector.

Dr Mukesh Agarwal, head of pediatrics at KEM Hospital in Mumbai said that the municipal teaching hospital is able to procure drugs like benzathine penicillin even though it is difficult to find in private facilities.

Benzathine penicillin is given as an injection once every 21 days to children suffering from rheumatic heart disease. Another option to treat the disease is with the an oral pill of erythromycin, which is the less preferred mode of treatment.

“The chances of defaulting on taking the medication is higher when the doctors prescribe the pill,” said Agarwal.

Even public hospitals that have better supply of first line antibiotics do not get as much of these medicines as required. Shortages sometimes compel pharmacists to give patients have the amount of medicine required for a five-day course and ask them to collect the remaining medicines after two days.

“The patient starts feeling better after two days of taking medicines,” said Dr Anita Kotwani, professor at the department of Pharmacology at VP Chest Institute in Delhi. “Will he come back to collect the rest of his dose? No. This suboptimal dose kills only half the bacteria in the body. The other half become resistant.”

Some antibiotics like doxycycline are easily available in combinations but not as single molecule formulations. “Combination drugs are more likely to cause drug resistance,” said Kotwani.

The price control factor

Kotwani has conducted several surveys on the availability and affordability of essential medicines. In 2013, just before the government released its Drug Price Control Order, she found that doxycycline was easy to find at both public and private health facilities in Delhi. In 2015, the drug, which had come under price control, was not as easily available. Drug manufacturers are less inclined to make drugs that are under price control and therefore less profitable than those for which prices are not regulated, said Jagannath Shinde, chairman of All India Organisation of Chemists and Druggists.

“After price control, companies feel that it is not affordable for them to produce the drug,” said Shinde. “They do not stop production. They just reduce the quantity of drugs they produce. Naturally, it will not be as easily available everywhere.”

The general availability or lack of antibiotics affects what medicines doctors prescribe.

“It is a vicious cycle,” said Dr Vijay Yewale, a pediatrician from Navi Mumbai and former president of Indian Academy of Pediatrics. Doctors stop prescribing antibiotics that are in short supply and, in turn, manufacturers make less of these antibiotics that doctors are no longer prescribing as much.

S Srinivasan, who runs a generic drug manufacturing company in Vadodara called LOCOST and is also part of the All-India Drug Action Network said that many of these first-generation antibiotics are “out-of-fashion”.

“Often the doctors fall prey to the marketing of the pharma companies,” said Srinivasan, about why some doctors might prescribe more advanced antibiotics.

Kotwani said that doctors also try to retain their patients with quick cures, prescribing what they call “effective” and expensive broad spectrum antibiotics instead of first line antibiotics.

Said Yewale: “There are some doctors who are not as rational in their prescription and have not upgraded themselves. If the patient is not very ill, why not try the simple narrow spectrum drugs first and check if it works?”