Antibiotics have played a pivotal role in modern healthcare. They have been instrumental in treatment and prevention of infections in various clinical settings, but effectiveness of antibiotics is decreasing which is largely because of development of antibiotic resistance. The development of generations of antibiotic -resistant microbes and their widespread distribution in microbes throughout the environment is because of many years of unremitting selection pressure from human and animal

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... tions of antibiotics. This is a manmade situation, and with the help of natural processes, superimposed on nature.' Until recently, the effects of antimicrobial resistance were not felt much as there has been a continuous stream of newer antibiotics. However, over the past 2 decades, there has been dearth of new antibiotics from pharmaceutical companies leading to inability to fight these MDR organisms.2 This marked increase in antimicrobial resistance among common bacterial pathogens is now threatening this therapeutic accomplishment, jeopardizing the successful outcomes of critically ill patients and is cause of severe infections, complications, longer hospital stays and increased mortality.' In fact, the World Health Organization has named antibiotic resistance as one of the three most important public health threats of the 21st century.4 ANTIBIOTIC RESISTANCE Antibiotic resistance refers to changes in bacteria that reduce or eliminate an antibiotic's ability to destroy it.' Drug resistance happens to almost every antimicrobial drug, not just antibiotics, and almost all pathogens and parasites, not just bacteria.' Evidence from various published data from around the world indicates an overall decline in antibiotic effectiveness: resistance to all types of antibiotics, including last resort, is rising.' The U.S. Centers for Disease Control and Prevention (CDC) estimates that at least 23,000 deaths and more than 2 million infections are because of antibiotic resistance each year in the United States. Total economic costs are also huge with estimated direct cost of $20 billion and additional productivity losses of $35 billion.' Similarly in Europe, an estimated 25,000 deaths are attributable to antibiotic -resistant infections, costing 1.5 billion annually in direct and indirect costs! UK government review recently estimated that deaths from Antimicrobial resistance could rise from approximately 70,000 to around 10 million yearly by the year 2050.9 Estimates indicate that more than 56,000 neonates die each year from resistance -attributable neonatal sepsis deaths caused by bacteria resistant to first -line antibiotics in India alone.19 MECHANISM OF RESISTANCE Antimicrobial resistance has been there since ages and it is because of the interaction between organisms and their environment. Since most antimicrobial compounds have been developed from natural molecules, the bacteria have evolved mechanisms to overcome their action in order to survive (Figure 1 ). Thus, these bacteria are often considered to be "intrinsically" resistant to one or more antimicrobials.4 However, in clinical settings, we are typically referring to the expression of "acquired resistance" in a bacterial population that was originally susceptible to the antimicrobial compound as the main focus of the problem. But this is a complex problem which will be described in following section.