It was 1928 when the Nobel Laureate Sir Alexander Fleming discovered the first antibiotic, penicillin. We have progressed a lot since then. With advancements in science and technology, new antimicrobials have been introduced and are being used to treat a variety of infections. Between 1940 and 1970, the so-called ‘golden era of antibiotics’, many antibiotics were discovered and during the late 1980s and early 1990s, two major groups of antibiotics, cephalosporins and fluoroquinolones, became available. However, with growing resistance to these antibiotics, colistin—once used in 1960s—linezolid, carbapenems, and tigecycline are currently being used.

Today, we have at least one type of microorganism which is at least resistant to all antibiotics available in the market. It may be time for us to recall what Dr Fleming had warned with the discovery of penicillin—“the time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug, make them resistant.” This is exactly what is happening today and we are again moving to a pre-antibiotic era, despite having hundreds of different antibiotics at hand. The achievements and the potential of antibiotics to benefit mankind are at a stake.

Repeated improper use

It, therefore, becomes important to understand why antimicrobial resistance occurs, how they spread and measures to prevent them from arising. Four mechanisms are well known. First, the bacteria ‘modify the antibiotics’ by producing antibiotic deactivating enzymes, rendering them ineffective. Second, some antibiotic-resistant bacteria ‘prevent the entry’ of antibiotics into the bacterial cell or ‘pump out’ the entered antibiotics, protecting the target of antibiotic action. Third, some bacteria alter the primary site of action of antibiotics, deferring the antibiotic to bind with targets in the bacteria. Finally, few bacteria produce an ‘alternate target’ for the antibiotics to bind to while continuing to produce the original sensitive target. This allows bacteria to survive as the antibiotic does not inhibit the alternative target and ‘bypasses’ the effect of the antibiotic.

With the increase in the availability and accessibility of the antibiotics over time, we have reached a state where antibiotics are in our pockets, bags, drawers, basically everywhere as our nutritional supplements. Moreover, antibiotics are extensively and irrationally used in humans, for agriculture and fisheries, and on animals. Every time a person takes inappropriate antibiotics, sensitive bacteria are killed and the resistant ones are selected, which then grow, multiply, and finally outnumber the sensitive ones. Repeated and improper (under) use of antibiotics are the primary causes for the increase in drug-resistant bacteria. Smart use of antibiotics is the key to controlling the spread of resistance.

A major risk

In the last two to three decades, the discovery of new antimicrobial agents has markedly slowed. Newer companies are not emerging and older companies are no longer spending as much on the research and development of newer antimicrobials. More and more companies are merging and they are interested in the research and development of drugs for chronic diseases like cancer. However, the emergence of bacteria resistant to existing antibiotics is on the rise along with prolonged stays in the hospital, treatment failures, spread of resistant pathogens to national and international borders, secondary complications, and economic, social, and mental aspects for patients as well as families.

In January 2013, the World Economic Forum warned that antimicrobial resistance is a major global health risk that the world needs to confront. They then called attention to the fact that losses of gross domestic product from antimicrobial resistance can range from 0.4 percent to 1.6 percent. The annual cost due to antibiotic-resistant infections in Thailand has been estimated to be around $2 billion. Undertaking such studies on the economic burden caused by anti-microbial resistance is important in Nepal as well.  

Studies have revealed that high rates of resistance have been observed globally in Mycobaterium tuberculosis, HIV, malaria parasite, Escherichia coli, Klebsiella pneumonia, Pseudomonas spp., Acinetobacter spp., Staphylococcus aureus etc. that cause myriad of infections. Tuberculosis is a public health emergency and nine million people developed tuberculosis in 2013. Of which, 480,000 people developed multi-drug resistant tuberculosis (MDR-TB), and nine percent of MDR-TB had extensively drug resistant TB. The emergence of TB among HIV infected persons has worsened the scenario of both diseases and furthermore, augmented the development of MDR-TB. HIV’s rapidly mutating property is also making it resistant to anti-retrovirals. Malaria is another disease of the poor complicating the situation and artemisinin resistance among the parasite (P. falciparium) is an urgent public health concern. In addition to these infectious diseases, resistance in pathogens causing infections of the respiratory tract, urinary tract, blood stream, and wounds are also emerging.  

Research or repent

Antimicrobial resistance is a grave problem and needs urgent attention in the three aspects. First, we need to ensure the appropriate use of antimicrobial drugs in medicine. This can be achieved by implementing regulations on the rational use of antimicrobials, changing prescriber and client behaviour in using antimicrobials, and massive advocacy in sectors beyond health, like veterinary, agriculture, fisheries, and industrial sectors where the misuse of antibiotics is rampant.

Second, we need to work on the prevention of drug resistant infections in the community and hospitals. For that, efficient antimicrobial surveillance systems need to be set up to understand the kind of microorganisms causing resistant infections and to take preventive measures like improving infection prevention and control practices, especially in hospitals where most nosocomial infections are due to resistant microbes. It is also important to improve availability and accessibility to quality diagnostic and drug resistance testing through quality assured microbial laboratory facilities.

Lastly, the Ministry of Health will need to focus on research and development to improve new antimicrobial drugs use in human medicine to inform policy on rational use of antimicrobials. Historically, the ministry’s investment in research has been feeble. Te time has come to reaffirm the government’s commitment to investing in research to provide effective and sustainable solutions to tackle antimicrobial resistance, not only for ourselves but for the next generation as well.

Mahat is a public health specialist and Thapa is a medical microbiologist