The discovery of the New Delhi superbug hit the limelight worldwide in 2008. It was found in the urinary tract infection of a Swedish patient of Indian origin who travelled to New Delhi in 2008. That organism produced the enzyme NDM-1 (New Delhi metallo-ß-lactamase-1) which was resistant to carbapenems - one of the most powerful antibiotics used to treat complex bacterial infections. Since then, many drug resistant organisms are emerging by the day and some of them are resistant to almost all antibiotics available till date.
With an estimated death of 1.27 million directly and five million deaths associated with antimicrobial resistance (AMR), it is becoming a global pandemic. AMR kills more people than cancer and road traffic accidents combined together. India is considered to be the AMR capital of the world, as on the one hand almost all the drug resistant pathogens are detected in India and on the other hand it is still fighting with old enemies like malaria, tuberculosis and cholera.
History of Antibiotics
The discovery of penicillin in 1928 opened the era of modern antibiotics. Since then, many groups of antibiotics were discovered and the discovery peaked around 1950. But then the pace of discovery of new antibiotics gradually declined and the emergence of drug resistant pathogens grew alarmingly. The detection of the first drug resistance organism in 1960 (MRSA or methicillin resistant staphylococcus aureus) heralded the onset of the AMR era.
In 2010, the United Nations declared AMR a ‘fundamental threat’. Ironically, the last new group of antibiotics developed was way back in 1987 and since then there is a discovery void. Currently, many multi drug-resistant organisms exist which are resistant to almost all available antibiotics including the most potent carbapenem and colistin.
Method of resistance development
Antimicrobial resistance is defined as the ability of germs like bacteria and fungi to defeat the drugs designed to kill them. As per the law of nature, survival of the fittest process helps the organisms to develop more drug resistant variants. Few organisms are inherently resistant to some antibiotics. But most drug resistance develops due to genetic mutation that helps organisms get the right combinations to survive in the presence of antibiotics.
The mutation may be single gene mutation or plasmid borne mutation. This way, the organisms develop various mechanisms to tackle antibiotics like development of efflux pumps to drive out antibiotics, loss of porin channels not to allow antibiotic entry, target enzyme alterations, cell wall lipopolysaccharide alteration and production of enzymes that can degrade the antibiotics. The production of various enzymes to disintegrate the antibiotics is the most powerful tool for development of AMR.
Magnitude of the problem
Resistance to Colistin, the most potent antibiotic available till date, was first detected in India. Currently the prevalence of Colistin resistance is as high as 46% according to few studies. Most of the organisms are now resistant to one or more commonly available antibiotics. The problem is alarming in hospital and ICU settings, where the use of multiple antibiotics is usual. Different studies say that the prevalence of multi drug-resistant organisms in ICU settings in India is up to 50%.
Risk factors for development of AMR
The more the use of antibiotics, the higher is the chance of development of AMR. Many modifiable risk factors are responsible for the development of AMR in India. Inappropriate use, overuse, inadequate dosing, improper selection of antibiotics and over the counter availability are the major concerns. Poverty, overcrowding, malnutrition and lack of awareness compound the problem. A survey says that India ranks first among all countries in the world for antibiotic use.
The way forward
Proper and strict antibiotic stewardship is the need of the hour to tackle AMR. Over the counter and self-prescription use of antibiotics need to be discouraged. Adequate education and awareness should be created regarding AMR. Also, health care personnel should be judicious in prescribing antibiotics. It should be remembered that all fever does not need antibiotics for cure. Whenever possible, antibiotic prescription should be culture sensitivity driven, narrow spectrum and target oriented. Use of broad spectrum and empiric antibiotic therapy should be minimised as it increases the probability of development of AMR. Proper dosing and proper duration of therapy is of paramount importance in preventing AMR. All health care institutes should develop an antibiotic use policy depending on their antibiogram.
Currently, the Government of India is taking necessary steps to curb antibiotic overuse and AMR. The current national action plan for antimicrobial resistance is comprehensive and aligns well with the WHO global action plan for AMR. Though hope is alive to fight AMR with newer antibiotics under development, still judicious use of already available antibiotics is the need of the hour.
The motto should be - Hit hard, hit right, hit complete.
(The author is a professor of general medicine at AIIMS, Bhubaneswar)