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A looming threat

MSS Murthy, Jan 12, 2016: 0:01 IST
Some drug resistant bacteria and the infections caused by them. Source: longitudeprize.org
Emergence of antibiotic resistance is increasing every year at an accelerating rate globally. MSS Murthy learns more about the phenomenon

Recent reports about the emergence of drug-resistant bacteria in hospitals across India indicate that it has emerged as an issue of concern. Antibiotic resistance is the growing resistance of bacteria to a drug that was originally effective for treatment of infections caused by them.

Resistance helps bacteria withstand fresh attacks by the drug and thus rendering the standard treatments ineffective. When a class of bacteria becomes resistant to a particular drug, the pharmacologist develops a new kind of antibiotic. In due course, the bacteria become resistant to the new drug as well.

Thus, over a period of time multidrug-resistant bacteria develop, making it a serious public health problem. Doctors have reported that a pathogen called Klebsiella pneumoniae, which causes urinary tract infection, pneumonia and sepsis has become resistant to the antibiotics carbapanems and colistin — these are considered to be the drugs of the ‘last resort’.

The situation, which may lead to higher mortality rates, is particularly bad for lymphoma and transplant patients with compromised immunity.

Understanding its working

To understand how bacteria acquire resistance to antibiotics, we have to first review how antibiotics work. They are designed to block some essential steps in the life cycle of the bacteria and prevent their further growth. They include cell-wall synthesis, folic-acid synthesis, DNA replication, RNA and protein synthesis.

Since many of these steps are common to host cells also (human and animal cells), the targets chosen are specific to the bacteria, so that the drug may not harm the host cells. The emergence of drug resistance permits bacteria to adopt counter measures to protect themselves.

Scientists point out that the evolution of antibiotic-resistant bacteria is a natural process. When the bacteria replicate themselves by billions, some may undergo mutations — changes in their genes. Some of these spontaneous mutations may provide resistance traits to the bacteria, so that they can thrive even in the presence of antibiotics.

The resistance itself comes in many forms. For example, a resistant bacteria may produce an enzyme that can bind to the drug and make it ineffective. Some penicillin-resistant bacteria produce an enzyme called beta-lactamase, which deactivates penicillin. Alternatively, the target to which the drug is designed to bind may be altered so that the drug may no longer be able to bind to it.

This can be seen in another type of penicillin-resistant bacteria. Some bacteria may reduce the permeability of the cell wall to the drug or alternatively increase the active efflux (pumping out) of the drug across the well wall so that it may not be available at a concentration high enough for it to be effective.

Bacteria can also scavenge resistance genes from dead bacteria, or acquire them through plasmids. Plasmids are independent DNA entities that live in bacteria. They carry several genes, of which some may be capable of providing antibiotic resistance to the bacteria. Bacterial species Klebsiella pneumoniae are known to have picked up the resistant gene through a plasmid.

The interesting aspect is that, all these resistance mechanisms involve genetic modifications so that the progeny will also be resistant to the drug. Thus, in a large population of bacteria, there will always be a few that have developed resistance to antibiotics.

When an infected person is treated with antibiotics, the susceptible ones perish, leaving behind the resistant ones, which will multiply at an opportunistic moment. Next time when the same antibiotic is given to the patient, it may not be effective in controlling the infection. What worries the doctors is the rapidity with which drug-resistant bacteria can spread through contaminated equipment or hands of caregivers in the hospital environment or outside.

Though antibiotic resistance is a natural phenomenon, there are several human activities which accelerate the process. Many antibiotics can be bought without doctor’s prescription, which encourages their misuse and over use. At the first sign of illness, many people just buy an antibiotic pill and swallow it. Even when duly prescribed by the doctor, many times patients do not take the full course.

Another important area is the rearing of livestock — where antibiotics are used (and misused) on healthy animals, not only to prevent diseases but also make them gain weight at a rapid rate. The residues of these may reach humans through improper handling and cooking of meat. All these ultimately lead to the thriving of resistant bacteria.

Recognising the seriousness of the problem, medical societies in India organised a joint meeting in August 2012 in Chennai. It looked at all aspects of the problem and suggested solutions in a report known as The Chennai Declaration: A road map to tackle the challenge of antimicrobial resistance. Antimicrobial is a broader term which includes bacteria, virus, fungi and many others. However, the Government of India is yet to come out with a national policy to contain the antimicrobial resistance.

Rising epidemic

The emergence of antibiotic resistance is a global problem, increasing every year at an accelerating rate. The World Health Organisation has developed a draft action plan to combat antimicrobial resistance which has been recently submitted to the 68th World Health Assembly. It also observed World Antibiotics Awareness Week between November 16 and 22, 2015 to increase public awareness. The organisation provides guidelines as to what everyone can do to help contain the problem of antibiotic resistance.

One of the most difficult aspects of diagnosing an infection is to ascertain, through quick and inexpensive tests, whether it is caused by bacteria or other microorganisms. Hence, Longitude — a charitable organisation based in London has instituted a GBP 10 million prize to whoever can develop “a point-of-care diagnostic test that can conserve antibiotics for future generations and revolutionise the delivery of global health care.”

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