Taking on the shape-shifters

14 min read
30 Mar 2017
14 min read
2230 words
The fight against antibiotic-resistant bacteria needs to be waged on multiple fronts

Sir Alexander Fleming’s discovery of penicillin in 1928 marked the start of the modern era of antibiotics. By the 1940s, the drug was already being widely used around the world. Penicillin went on to save the lives of thousands of soldiers wounded in the Second World War, and it also rescued from the cusp of death thousands suffering from bacterial infections. Antibiotics was soon called the miracle drug. But only a few years later, Staphylococcus, a bacteria resistant to penicillin had already been discovered. The long battle against antibiotic resistance had begun.

For bacteria, being attacked is something they have lived with forever. For the billions of years that they have been on earth, they have always had to fend off attacks from different organisms. And in order to survive the attacks, bacteria developed resistance. The scientists and doctors who used the first antibiotics to attack infection-causing bacteria in humans knew that with time, bacteria would develop resistance to these drugs. But what they had not anticipated was the alarming pace with which antibiotic resistance would go on to develop.

In 2015, a report published by the National Center for Biotechnology Information (NCBI), in the US, showed the pace with which bacteria have developed resistance to different antibiotics introduced over the years. Resistance to tetracycline, an antibiotic introduced in 1950, was discovered in 1959, while resistance to methicillin—introduced in 1960—was discovered in 1962. Resistance to ceftaroline, an antibiotic introduced in 2010 and used mainly to treat pneumonia and skin infections caused by bacteria, was discovered in 2011. The primary reason behind the rapid pace of bacteria’s becoming antibiotic-resistant has to do with the arbitrary use of antibiotics in animals and humans. In Nepal, where antibiotics are available for purchase without prescription, and are widely used on animals meant for human consumption, antibiotic resistance can become an unmanageable issue. Experts say efforts thus need to be made to contain the problem before it gets out of hand.

Alarming findings

At the forefront of the antibiotic-resistance research in Nepal is Global Antibiotic Resistance (GARP-Nepal). According to GARP-Nepal, a nine-year study by Geeta Shakya and Bal Ram Adhikari (1999 to 2008) on Streptococcus pneumoniae, a pathogen that causes pneumonia, collected from 11 laboratories around Nepal, showed the antibiotic-resistance capacity of cotrimoxazole and ciprofloxacin had been increasing from 2000 to 2008.  Another study, by Sarala Malla, (published in 2014) found that Neisseria gonorrhoeae, the bacteria that causes gonorrhoea, a sexually transmitted disease, had 14 to 30 per cent resistance to ciprofloxacin.

Another study, by Salman Khan, Priti Singh, Asnish Asthana, Mukhtar Ansari in 2014, came up with similar findings. The study conducted on antimicrobial resistance patterns of Shigella, a major diarrhoeal disease-causing pathogen in Nepal, at Nepalgunj Medical College and Teaching Hospital, Banke, from September 2011 to March 2013, showed increased resistance to major antibiotics such as nalidixic acid, ampicillin, cotrimoxazole and ciprofloxacin.

“Antibiotic resistance is not being taken seriously to the extent that it should,” says Dr Buddha Basnyat, a consultant clinician at Patan Hospital. “This attitude prevails even though doctors in Nepal are increasingly seeing cases of regular antibiotics not working against common bacteria that cause chest infections, fevers and urinary tract infections. But most doctors have no choice but to prescribe stronger antibiotics. It is a massive problem globally as well as locally.” What makes matters worse, says Dr Basnyat, is that in the next seven to eight years, new antibiotics are highly unlikely to be rolled out. It makes much more sense for drug companies to come up with drugs for chronic illnesses like high blood pressure, cancer and diabetes (where patients have to take drugs for a long period of time) than antibiotics (because patients only have to take antibiotics for a limited period of time).

“To fight the bacteria, all we have in our arsenal today is what we will have in the near future as well,” says Dr Sameer Mani Dixit, cofounder and vice chairperson and director of research at Centre for Molecular Dynamics-Nepal (CMDN). “But because of the pace at which the bugs are becoming resistant to the antibiotics we have, and because there is very slim chance of new drugs coming our way, we risk losing the antibiotic war.”

How antibiotics work and how bacteria become resistant to them

Most antibiotics work by destroying the bacteria’s cell walls—the wall is responsible for holding the whole of the cell together—or by destroying a bacterial cells’ lipids and proteins, thus damaging the cell’s DNA and stopping them from reproducing. “But when you underdose, you give pathogens the opportunity to become resistant to the antibiotic,” says Dr Santosh Dulal, scientific manager at CMDN. Underdosing occurs when a patient who has been prescribed an antibiotic stops taking the medicine prematurely. Say, a doctor has prescribed that a patient take an antibiotic for five days, but the patient, after taking it for three days—when the drug has killed, say, 70 per cent of the bacteria—starts feeling better and stops taking the drug. That means there still remains inside his body the tougher, 30 per cent of the bacteria that have survived the first three days, but which would have otherwise been killed completely had the patient completed the course of the antibiotic. “So what remains in the patient’s body are the most-resistant pathogens. These then start multiplying, and the next time the person becomes sick and takes the same antibiotic, the bugs have already become resistant to treatment by then and are not affected,” says Dr Dulal.

Another factor that’s responsible for the rapid growth of antibiotic resistance has to do with misprescription of antibiotics. Antibiotics only work on bacterial infections. They do nothing for viral infections. Most antibiotic misprescriptions occur when a doctor is unable to determine whether an infection is viral or bacterial. Even though there are tests that can be done to distinguish between the two types of diseases, these tests are mostly expensive and in some cases, need multiple days to produce results. “What we need are cost-effective, quick and easy-to-perform Rapid Diagnostic Tests (RDT) that determine whether an infection is viral or bacterial. These will play a huge role in reducing antibiotic misprescription,” says Dr Basnyat. “There’s yet another problem. We are a society that’s gotten too used to resorting to antibiotics instantly; thus, if a doctor doesn’t prescribe antibiotics to a patient, he or she would rather find another doctor who will, or worse, go to a pharmacy and buy antibiotics over the counter.” Pharmacies have a significant role to play in the fight against antibiotic resistance because in Nepal, except for serious illnesses, people generally head over to local pharmacies for medication and because antibiotics can be purchased there without prescription.

“Antibiotics like imipenem, a last-resort antibiotic, which is prescribed only when all other antibiotics have failed, can be bought without prescription,” says Dr Basnyat. “We have focused so much on doctors and hospitals that we haven’t taken into account the important role local pharmacies play in countering the problem. It’s very important for us to get them onboard in this fight.”

When a patient is wrongly prescribed an antibiotic, it doesn’t do him/her any immediate harm. The antibiotics not only kill bad bacteria; they also kill the ‘good’ bacteria present in the body. The good bacteria in our body help with digesting food, absorbing nutrients and preventing bad bacteria from creating colonies in the body. The impact on good bacteria is worse if the antibiotic prescribed is a broad-spectrum antibiotic; broad-spectrum antibiotics attack different types of bacteria, which then activate multiple bacteria to become resistant to the antibiotic. “Implementing ‘antibiotic stewardship’ is another way that we can tackle this problem,” says Dr Dixit. “Under an antibiotic stewardship programme, young doctors are only allowed to prescribe antibiotics to patients after consulting with senior doctors. Antibiotic stewardship should be practised much more widely than it is today.”

“We have focused so much on doctors and hospitals that we haven’t taken into account the important role local pharmacies play in countering the problem. It’s very important for us to get them on board in this fight”

Hospitals have a larger role to play than just stemming misprescribing. Hospitals themselves are a breeding place for antibiotic-resistant pathogens, and it is very important that hospitals are kept extremely clean. “In a country like Nepal, where many hospitals and health facilities don’t follow the World Health Organisation’s (WHO) guidelines on Prevention and Control of Hospital Associated Infections, which are required of such institutions, such lapses pose a serious problem,” says Dr Dixit. “And people are more likely to get hospital-acquired infections (HAI) in hospitals that have surgical wards, where surgical equipment and utensils aren’t sterilised properly.” Unsurprisingly, in Nepal, cases of people acquiring HAIs are quite a common phenomenon. Some of the more common HAIs in Nepal are pneumonia, urinary tract infections, septicemia, meningitis, diarrhoea caused by Klebsiella (a pathogen), bloody diarrhoea, severe anemia and even kidney failure caused by harmful E. coli.

Rampant use of antibiotics on livestock

The extensive use of antibiotics on livestock meant for human consumption is another issue that needs to be addressed. In many farms in Nepal, antibiotics are mixed with animal feed to prevent livestock from getting sick and to promote their growth. According to a GARP-Nepal study, the volume of veterinary antibiotic sales in Nepal rose by over 50 per cent from 2008 to 2012, most of which were sold by retailers who did not have a veterinarian prescription. Just like in humans, when animals are exposed to antibiotics for a prolonged period of time, the bacteria in their body develop resistance to these antibiotics. These resistant bugs can then get transferred to humans when they come in contact with the animals—when humans eat their meat and when the animals’ excretions are released into the environment. “This is a very grave issue. The government needs to document the antibiotics being used in the livestock sector,” says Dr Basnyat.

What can be done

Many studies have shown that a bacteria’s ability to resist antibiotics decreases when it hasn’t been exposed to antibiotics for a long period of time. This means resistance is reversible. Bactrim, an antibiotic, used to treat typhoid fever was dismissed years ago after bacteria started becoming resistant to it. “But bactrim is now showing effectiveness again, and bacteria that were once insensitive, have now become sensitive to the drug,” says Dr Basnyat. “Of course the best thing would be to not take antibiotics in the first place.”

Conducting childhood immunisation drives against common diseases like the flu, diarrhoea, tuberculosis and cholera would also help. And so would encouraging people to drink only sterilised water, maintain hygiene and stop open defecation.

In the more developed countries, banning the sale of antibiotics without prescription has been the chosen method for tackling antibiotic resistance. But that approach isn’t likely to work in a developing country like Nepal. “In a country like ours, thousands die of bacterial infection in remote villages every year; these deaths could have been easily prevented had they had access to antibiotics. Creating a blanket law that bans sales of antibiotics without prescription isn’t the most practical thing to do here. It’s a matter of access vs excess,” says Dr Basnyat. “What we could do is ban sales of antibiotics without prescription in cities and towns, but not in villages.”

Experts believe that the overall battle against antibiotic resistance needs to be waged on several fronts.  “In order to do that, the government needs to start creating stringent rules and laws to contain the inexorable force that antibiotic resistance has become,” says Dr Basnyat. “And then everyone needs to work together to ensure that those rules are followed.”