How Kerala is fighting the superbugs

For a senior citizen like Gopalakrishnan, AMR could prove to be fatal. The professor was surprised for he had faced no hurdle in obtaining the antibiotic drug from a local pharmacy, whenever he wanted to.

Gopalakrishnan represents a vast majority of Kerala’s educated population that purchases antibiotics over the counter (OTC), quite unaware that it is illegal to do so. Now, the government of Kerala intends to put an end to the practice. Last month, it decided to curb OTC sale of antibiotics by medical shops. “No antibiotics can be sold in the state without a doctor’s prescription," said Veena George, state health minister, following the annual review meeting of the Kerala Antimicrobial Resistance Strategic Action Plan (KARSAP). She further warned that the licence of pharmacists who made OTC sale of antibiotics would be cancelled. Also, to make the state 100% antibiotic literate, the government has already come up with an antibiogram (data that assesses local prevalence and susceptibility of pathogens), kicked off an awareness campaign and involved other departments like animal husbandry and poultry to take on the menace of AMR.

What is AMR

As Kerala leads the fight against AMR, its intent is laudable but implementation of stringent measures is likely to be a challenge. Nevertheless, it is imperative to understand why the fight itself is an important one. In Kerala, the irrational use of antibiotic drugs is seen as a prime driver of antimicrobial resistance by the state’s AMR Surveillance Network. Apart from this, poor hygiene and sanitation, antimicrobial use in agriculture and poultry, a woeful lack of vaccines and newer antibiotics, and inadequate infection control practices in hospitals add to the AMR problem.

According to The Lancet, AMR has surpassed HIV/AIDS as the world’s leading cause of death. Such resistance caused the direct death of 1.2 million people in 2019 alone and, indirectly, another 4.95 million. Low- and middle-income countries are considered to be the hotbed of this growing public health threat and global healthcare agencies have started implementing action plans to tackle it.

The overuse, misuse and abuse of antibiotic drugs leading to AMR is not a regional but a national problem. According to a 2022 study, at the national level, total private-sector antibiotic consumption increased by 12.0% between 2011 and 2016, from 4,749 to 5,358 million DDDs (defined daily dose), and then decreased to 5,071 million in 2019, registering a net increase of 6.8% between 2011 and 2019 and a CAGR (compound annual growth rate) of 0.63%.

Kerala’s attempt at containing it, should it succeed, could lay the template for the rest of the country to follow.

Kerala’s surveillance

In India, a programme to contain antimicrobial resistance was launched in 2017. Under this, three states—Delhi, Madhya Pradesh and Kerala—set up their AMR surveillance networks. Kerala has now come up with its annual report of 2021—an antibiogram—which is the first of its kind in the country. This includes AMR surveillance data pertaining to seven priority pathogens, received from 18 surveillance laboratories across nine districts.

“It was a herculean task amid the pandemic as we needed a network of laboratories for this surveillance. Curbing the OTC sale of antibiotics is not a new rule. We are just trying to implement national guidelines," says Dr R Aravind, convenor of the KARSAP working committee. All antibiotic drugs come under schedule H meaning they cannot be sold without a medical prescription. “What we need is a comprehensive antibiotic literacy drive educating common people, doctors and pharmacists. The after-effects of AMR should be included in school curriculum so that the future generation is properly educated," he adds.

Burden of education

But the big question is: will a government directive to curb OTC sale of antibiotics work? Dr Anoop Kumar A. S., a senior consultant in critical care based in Kozhikode, is not too sure. “This is just an eyewash. In a society like ours, it’s not easy to put curbs on antibiotic sales. Here, everybody searches Google for their ailments and advises the doctors for particular treatments. It is a fact there is pressure from patients to prescribe antibiotic drugs. It’s a kind of negative effect of being educated."

In a state like Kerala, where hospital access is easy and period of hospitalization is comparatively high, such an advantage also works against the AMR situation.

Most often, it’s during hospitalization that patients get infected by drug-resistant pathogens. There is also a tendency to give high-end antibiotics to VIP and trauma patients. “Similarly, surgical patients are given irrational doses of antibiotic drugs. In normal cases during pre-surgery, a single dose of antibiotic is enough, but we tend to give a five-to-seven-day course of the drug. These tendencies among doctors should also be audited and curbed," says Kumar.

Pathogens in hospitals

A survey carried out by the Indian Council of Medical Research (ICMR) in 2021 to determine antibiotic resistance across the country showed that healthcare associated infections (HAI) and urinary tract infections are common in Indian hospitals and the pathogens causing HAI are highly drug resistant. A high rate of resistance was seen against antibiotics, including third generation cephalosporins, carbapenems, fluoroquinolones and aminoglycosides, in bacteria such as Klebsiella pneumoniae (which causes pneumonia, bloodstream infections, surgical site infections and meningitis), Escherichia coli and Acinetobacter baumannii, a bacteria known to cause infection in the blood, urinary tract and lungs among others.

A government doctor in Kochi admitted that there are many cases where they know patients would have responded better to medicines if they had not developed AMR, but they cannot say this with certainty or go on record with such data.

“Patients who need long stretches of hospitalization, especially intensive care, are more prone to AMR. In a state like Kerala, the numbers will be on the higher side," says Kumar.

In 2017, ICMR had issued certain guidelines for antimicrobial use in ailments, aiming to rationalize the usage of antibiotics and establish consistency in the treatment of various infectious conditions.

“Ideally, we should use narrow spectrum antibiotics (that kill or inhibit specific bacteria) for specific infections. It’s not practical to do a bacteria culture test on every patient. But our common practice is to go for a broader spectrum antibiotic even before identifying the bacteria causing the infection. There would be doctors who are not sure about their diagnosis and end up prescribing such antibiotic drugs. I don’t think there is any corporate pressure on doctors to prescribe these, but this is the usual practice," says Dr N.M. Arun, who works in the government health service.

Impact on pharmacies

The pandemic only worsened the rampant use, or rather misuse, of antibiotics. Azithromycin, in fact, overtook insulin as the best-selling drug in India post covid. In such a scenario, the role of pharmacists and law enforcers becomes all the more crucial.

“We will have to be careful in dealing with the situation," says a pharmacist in Kochi, adding, “There would be some initial problems when we stop selling antibiotics over the counter. Though illegal, its sale has been happening for years. If the government creates proper awareness among patients and doctors, it will automatically stop. We are not the only guilty party in this."

Moreover, enforcement can happen only if there is manpower. “We do not know how the government directive is going to be implemented. The department does not have adequate staff strength to conduct regular inspections across pharmacies," says an officer with the Kerala drugs control department. Apart from the state drugs controller and a deputy controller, there are only six regional drugs controllers, seven assistant drugs controllers and 47 drugs inspectors across the state. He added that since 2000, not a single official has been appointed in the department.

In Kerala, there were only about 10,000 pharmacies before 2000. Now the number has gone up to 26,000, says P.M. Jayan, the state drugs controller. “Last week, we carried out a statewide raid and discovered some irregularities," he adds.

Staff shortage and operational difficulties should not be an excuse, believes Aravind.

“No one, including practising doctors, can buy psychotropic drugs or sleeping pills over the counter. How is this possible? Because the pharmacy owners know their licence will be withdrawn if they sell these drugs without prescription. Such a move should be in place for antibiotics too," he says.

Rising inefficacy

However, a month after the government directive, this reporter managed to buy a strip of Azithromycin from a Kochi pharmacy without any prescription. For the medical fraternity, what is particularly worrying is the rising inefficacy of the medicines and the absence of alternatives, which makes the case to restrict access to antibiotics more urgent.

“According to many studies, the resistance of pneumococcal bacteria to Azithromycin, which was 2- 3% until 2010, has gone up to 40% last year, making them practically ineffective in treating pneumonia," says Dr Aravind.

The ICMR survey found that 87.5% samples of A. baumannii were resistant to carbapenems, a last-line antibiotic mainly used in hospitals to treat pneumonia and septicemia. Among diarrhoeal pathogens (diarrheagenic E. coli, Shigella spp. and Salmonella), norfloxacin susceptibility was poor.

Since carbapenems are the last-resort antibiotics, KARSAP is looking at declaring the isolation of carbapenem-resistant bacteria through culture studies a notifiable condition. Any hospital which finds carbapenem-resistant bacterial isolate in labs would have to immediately report it to the health department. Earlier in 2020, a study by researchers of Kerala University of Fisheries and Ocean Studies had found carbapenem-resistant Enterobacteriaceae in water bodies and farms near hospitals in Kerala.

Beyond humans

The indiscriminate use of antibiotics is not restricted to humans. It has also been found in animal husbandry, poultry farming, fish farming, etc. Antibiotic-resistant bacteria and genes have also been detected in samples collected from the environment. The unscientific use of antibiotics in all sectors has led to this situation, the state health department warned in November 2022.

In a 2020 presentation, Dr. Sarada Devi K.L., state nodal officer for AMR, had pointed out certain Kerala-specific AMR challenges, including antibiotic use in animal husbandry, use of animal manure in soil, inadequate treatment of effluents containing antibiotic residue from pharma industry and improper waste water management. She had suggested identifying environmental sources of infection, improving housekeeping at hospitals and ensuring appropriate bio-medical waste management to curb this menace.

Dr Sagar Khadanga, nodal officer of the technical committee for Madhya Pradesh State Action Plan on AMR, believes it’s time to re-strategize priorities with a holistic, multi-sectoral approach. “Analysing action plans of the three states through the lens of ‘One Health’ (which acknowledges the close relationship between the health of humans, animals and their shared environment), it seems there are only passing remarks about inter-sectoral action plans with measurable outcomes. Kerala is the best among the three," Dr Khadanga observed in a 2022 review article.

Antibiotic literacy

According to health professionals, AMR initiatives must include professionals from all disciplines related to the issue.

This is where antibiotic literacy comes into play, says Aravind. “Achieving 100% antibiotic literacy not only means teaching the public, but ensuring every stakeholder is made aware of this menace through various campaigns. There are doctors who prescribe antibiotics unnecessarily and pharmacists who sell them over the counter. Both of them should be held more responsible than a common man who comes to buy it," he adds.

Given that most people in Kerala are aware of drugs and their uses, the issue requires a multifaceted strategy. Apart from enforcement, the government has already kicked off an awareness campaign setting 100% antibiotic literacy as its goal. This covers all aspects of AMR education, training, communication and information campaigns across human health, animal husbandry, fisheries, dairy and other sectors.

As the superbug pandemic silently plays out, Kerala has taken the first step on a very long, lonely road.