Overuse of Antibiotics and Antibiotic Resistance in Medical Applications Featuring Carbapenemase Resistant Enterobacteriaceae (CRE)

The decreasing effectiveness of antibiotics in treating common infections results from the spread of antimicrobial resistance (AMR), and is building up to become an epic global public health crisis. Extended periods of antibiotic overuse and misuse since their introduction have applied strong selective pressure towards high-level AMR and Multiple Drug Resistance (MDR), rendering entire classes of antibiotics ineffective. The primary driving force for this global AMR pandemic is the widespread misuse and overuse of antibiotics, in both medical and nonmedical applications. Antibiotics have been misused in all of their applications, including [1]: • Hospital and outpatient use by physicians through unnecessary, indiscriminate or incorrect prescribing. • By patients, through incorrect dosing and course durations. • Large-scale use in agriculture for disease treatment, prophylaxis and growth promotion in animal husbandry and food production. These actions not only have provoked the emergence of resistant microbes, but also have provided optimal environments for the spread of and selection of resistance determinants. It has been established in many countries that the levels of antibiotic consumption consistently correlate with levels of antibiotic resistance (i.e. the more antibiotics are being used in a population, the more resistance to antibiotics there will be in bacteria responsible for infections in that population). Of particular concern is the development and spread of Carbapenem-resistant Enterobacteriaceae (i.e CRE) [2]. The global emergence of carbapenemase-producing organisms is a public health emergency because these enzymes confer resistance to both carbapenems and nearly all β-lactam antibiotics, and are often associated with multidrug or pandrug resistance [3,4]. Resistance to antibiotics mediated by acquired carbapenemase enzymes in gram-negative bacteria – principally the Enterobacteriaceae species is a serious public health concern. Most Carbapenemaseproducing isolates of Enterobacteriaceae are resistant to multiple other classes of antibiotics, limiting therapeutic options to patients. Since the carbapenem antibiotics are the last line of defense against multidrug-resistant gram-negative bacterial infections, their vulnerability represents a real public health crisis. This article will focus on the overuse of antibiotics through medical applications. Antimicrobial Resistance (AMR): A Global Public Health Crisis The Age of Antibiotics: Prior to the discovery of penicillin as the first available antibiotic, infectious disease had been the leading cause of death throughout history. Penicillin was the first successful chemotherapeutic agent produced by microbes and it initiated the age of antibiotics. It represents the first therapeutic agent that destroyed bacteria in vivo, was not destroyed in the body, and was non-toxic to humans. Penicillin belongs to the beta-lactam class of antibiotics, which are the most successful natural product group used in chemotherapy. Later developed members of this antibiotic class which are widely used in medicine today include the orally active semisynthetic penicillins (ampicillin, amoxicillin) and the cephalosporins. It has been estimated that at the end of the nineteenth century, nearly one third of all deaths were due to infectious disease. By the end of the twentieth century, the death rate from all sources of infection dropped to levels well below 10% [3]. No other class of medicine has had a comparable cumulative impact on reducing death rates and increasing life spans [4]. The Spread of Antimicrobial Resistance (AMR): The world is now entering the post antibiotic age because of the growing problem of Antimicrobial Resistance (AMR). Infections from resistant bacteria have become more common and some pathogens have become resistant to multiple classes of antibiotics. The spread of AMR threatens to compromise the treatment of all infectious disease and is one of the most serious problems confronting both contemporary and future global public health. The World Health Organization (WHO) had proclaimed