Antibiotic mismanagement - A sleeping bomb

Dr Debapriya Mukherjee *

Today it is beyond our imagination that mild to moderate bacterial infection is untreatable and causes death. But mismanagement in antibiotic use is accelerating the natural process of evolution and mutation in bacteria - a phenomenon known as antibiotic resistance (ABR). This ABR poses a colossal threat to global health and incurs high economic costs to the society.

The convergence of factors such as poor public health infrastructure, rising incomes, a high burden of disease, and cheap, unregulated sales of antibiotics has created ideal conditions for a rapid rise in resistant infections in many countries including India, Sri Lanka, Bangladesh, Nepal, Bhutan and Pakistan.

Currently, every year, 700 000 patients die globally on account of ABR. This death toll will increase to 10 million by 2050, which would lead to a reduction of gross domestic product (GDP) by at least 2.5%.

Over-the-counter, nonprescription sales cause the resistance to antibiotics as “one of the most significant threats to patients’ safety worldwide. This may be attributed to the limited availability of well trained pharmacists in many pharmacies in these countries despite the government regulations. Poor enforcement of the law and regulations is the most likely factor to the limited availability of pharmacists.

Antibiotics are often the go-to prescription for many primary care cases, but as much as 23% of these prescriptions could be inappropriate. Higher antibiotic consumption can lead to drugs becoming ineffective at combating infections. Self-medication with antibiotics purchased without a prescription is common practice, particularly in these countries.

Self-medication involves obtaining medicines without a prescription, resubmitting old prescriptions to purchase medicines, sharing medicines with relatives or members of one’s social circle, or using leftover medicines stored at home. The inappropriate use of antibiotics through self-medication may cause signi?cant adverse impacts such as antibiotic resistance, treatment failure, and drug toxicity.

Inappropriate drug use in self-medication includes taking inadequate doses, sharing medicines, a short duration of treatment, and stopping treatment upon the improvement of disease symptoms. The appearance of multidrug-resistant bacterial strains, which are highly resistant to many antibiotic classes, has raised a major concern regarding antibiotic resistance worldwide.

This resistance may result in longer-lasting illnesses, more doctor visits, extended hospital stays, the need for more expensive medications, and even death. More than 50% of antibiotics are purchased without a prescription and used over-the-counter in most parts of the world.

In addition to drug resistance, the commonly used antibiotics have adverse impacts on the ecology of both the gut and the oral micro biome as observed in many adults. The fecal micro biome is also severely affected by antibiotics.

The antibiotic in the environment originating from waste water treatment plants serving antibiotic manufacturing facilities causes the transfer of resistance genes into human micro biota and pose a serious threat to antibiotic effectiveness. Antimicrobial residues in food animal products (such as chicken meat and milk) indicating that antibiotic use in food animal production is widespread. Practically there are no regulations governing the discharge of antimicrobial waste into the environment or presence of antibiotic in these foods.

Antibiotic use in India went up from 3.2 billion defined daily doses (DDD) to 6.5 billion in 2015. Factors which contribute to antibiotic malpractice may have a geographical variation due to di?erences in human behavior, health literacy, economy, and legal provisions, not allowing the generalization of ?ndings from elsewhere.

In Sri Lanka, about 12.7% of the total estimated annual health budget (about US $22 million) is spent on antimicrobials. The scale-up in antibiotic use has been enabled by rapid economic growth and rising incomes but that could not enable the improvements in water, sanitation, and public health, although evidence exploring this key issue is anecdotal.

Antibiotics continue to be prescribed or sold for diarrheal diseases and upper respiratory infections for which they have limited value. Of course, patient expectations relating to antibiotic treatment puts pressure on clinicians to prescribe antibiotics when they are not necessary. The large population is often blamed for the easy spread of resistant pathogens, but population densities in the developing countries cannot be granted as the major cause.

The main obstacle is that these countries lag on basic public health measures as well as fault in health system. Doctors routinely receive compensation from pharmaceutical companies and pharmacists in exchange for antibiotic prescriptions. The current antibiotic dispensing practice poses not only a serious challenge to the appropriate antibiotic use in the country, but may also be associated with signi?cant adverse drug reactions (ADRs) from the antibiotics, high treatment cost and complications of infections due to inappropriate treatment with antibiotics, and can impact global ABR and related consequences.

The fight against ABR is constant, and the discovery of new antibiotics is critical. Together, the facts and statistics raise an important question: is the time of antibiotics up? Although antibiotics have served humanity well for the last 70 years or so, the ability of bacteria to quickly evolve has made it imperative to look for other options.

To combat rising antimicrobial resistance, improve access and clinical outcomes, and preserve the effectiveness of antibiotics WHO (World Health Organization) adopted a new classification for antibiotics. This new model comprises three categories: Key Access antibiotics that “should be widely available, affordable and quality assured”; Watch Group antibiotics recommended only for specific, limited indications; and Reserve Group antibiotics for situations when all alternative antibiotics have failed.

Reduction in the use of antibiotics represents a huge challenge in all these countries particularly India that is a major drug producer and has some of the highest sales of antibiotics globally and highest levels of antimicrobial resistance.

Contributing factors to these high sales include failures of India’s drug regulatory system (which have been identified in government reports) the sale of antibiotics without prescription, and the proliferation of fixed-dose combination (FDC) antibiotics, many of which are not approved in other countries or by India’s national regulator, the Central Drugs Standard Control Organization (CDSCO).

FDCs are formulations comprising two or more drugs combined in a fixed ratio of doses and available in a single dosage form. FDCs that are composed of two antimicrobial drugs, especially drugs with mismatched dosing regimens, are concerning in the context of antimicrobial resistance. Over-the-counter access to antibiotics is a problem, but regulations to restrict access have to be balanced against the need to maintain access for the significant proportion of the population that lacks access to doctors.

Indeed, lack of access to effective and affordable antibiotics still kills more children in developing countries than does drug resistance. The background burden of bacterial infections, and misuse for all fevers regardless of whether they are caused by parasites, viruses or bacteria, is another major causal factor. Under the Swacch Bharat Abhiyan (Clean India Program), the government has committed to providing toilets and improving sewage systems to reduce burden of bacterial infection, but these measures will take time to implement.

Now there is emergent need to ensure that the rules and regulations stipulated by respective government are implemented to stop over-the-counter sale, irrational prescriptions and self-medication. However, drug control authorities in all these countries are trying to build awareness about the problem among professional bodies, the media, policy makers, and the lay public.

Despite the initiatives already taken, the most challenging task to impose restriction on inappropriate use of antibiotics is to improve the capacity of drug regulatory bodies to safeguard against powerful antibiotics being sold over the counter and to phase out the use of antimicrobial growth promoters in livestock. These capabilities are also needed to ensure the safety and reliability of India’s pharmaceutical manufacturing sector, which now supplies a significant proportion of the world’s pharmaceutical needs.

Also behavior change is needed among physicians and patients. In this context it is pertinent to mention that many countries have achieved remarkable reductions in smoking in buildings, workplaces and public places through regulation and behavior change communication.

Similar campaigns may work to educate the public and physicians about the dangers of uncontrolled antibiotic use through mass media in efficiently targeting public education programmes, as has been the case in high-income countries, but more research is needed to see how well this could work in India and neighboring countries. There is urgent necessity to change the rules under which physicians can accept compensation on prescribing antibiotics.

Another important task is to collect adequate data for evaluating the extent of resistance. The Indian Council of Medical Research has established a National Programme on Antimicrobial Surveillance in ten laboratories based at academic centers and covering priority pathogens identified by the World Health Organization.

This surveillance data on antibiotic consumption must be interpreted with sound scientific evidence to help in prudent use of antibiotics through medical supervision and prescription in order to combat the unwanted antibiotic side effects including emergence of antibiotic resistant bacteria from antibiotic misusage. This move would send a strong signal of the country’s commitment to tackle this issue.