Enlist various mechanisms of drug resistance & describe any two mechanisms in detail.
Answers
Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens.
INTRODUCTION
The discovery, commercialization and routine administration of antimicrobial compounds to treat infections revolutionized modern medicine and changed the therapeutic paradigm. Indeed, antibiotics have become one of the most important medical interventions needed for the development of complex medical approaches such as cutting edge surgical procedures, solid organ transplantation and management of patients with cancer, among others. Unfortunately, the marked increase in antimicrobial resistance among common bacterial pathogens is now threatening this therapeutic accomplishment, jeopardizing the successful outcomes of critically ill patients. In fact, the World Health Organization has named antibiotic resistance as one of the three most important public health threats of the 21st century (1).
Infections caused by multidrug-resistant (MDR) organisms are associated with increased mortality compared to those caused by susceptible bacteria and they carry an important economic burden, estimated at over 20 billion dollars per year in the US only (2,3,4). The Centers for Disease Control and Prevention conservatively estimates that at least 23,000 people die annually in the USA as a result of an infection with an antibiotic-resistant organism (5). Moreover, according to a recent report, antibiotic resistance is estimated to cause around 300 million premature deaths by 2050, with a loss of up to $100 trillion (£64 trillion) to the global economy (6). This situation is worsened by a paucity of a robust antibiotic pipeline, resulting in the emergence of infections that are almost untreatable and leaving clinicians with no reliable alternatives to treat infected patients.