Health care professionals are concerned over the rise in antibiotic resistant ba

Question

Health care professionals are concerned over the rise in antibiotic resistant bacterial strains. Exposure to antibiotics presents a selective environment that favors the evolution of resistance in bacteria. Which lines of evidence suggest that antibiotic resistance evolved a long time ago in bacteria (pre-dating the use of antibiotics by humans)? How and why has antibiotic resistance evolved in bacteria prior to exposure to antibiotic use by humans? What role does exposure to modern antibiotics play in the evolution of antibiotic resistance genes and mechanisms? Based upon the study by Baym et al. 2016, how does the evolution of antibiotic resistance in different bacterial strains inform drug discovery and better design of antibiotics and antimicrobials for human pathogens?

Explanation / Answer

The most striking examples, and probably the most costly in terms of morbidity and mortality, concern bacteria. The discovery of these infectious agents in the late 19th century stimulated the search for appropriate preventative and therapeutic regimens; however, successful treatment came only with the discovery and introduction of antibiotics half a century later. Antibiotics have revolutionized medicine in many respects, and countless lives have been saved; their discovery was a turning point in human history. Regrettably, the use of these wonder drugs has been accompanied by the rapid appearance of resistant strains. Medical pundits are now warning of a return to the preantibiotic era; a recent database lists the existence of more than 20,000 potential resistance genes (r genes) of nearly 400 different types, predicted in the main from available bacterial genome sequences . Fortunately, the number existing as functional resistance determinants in pathogens is much smaller.

Many of the bacterial pathogens associated with epidemics of human disease have evolved into multidrug-resistant (MDR) forms subsequent to antibiotic use. For example, MDR M. tuberculosis is a major pathogen found in both developing and industrialized nations and became the 20th-century version of an old pathogen. Other serious infections include nosocomial (hospital-linked) infections with Acinetobacter baumannii, Burkholderia cepacia, Campylobacter jejuni, Citrobacter freundii, Clostridium difficile etc.The most prevalent Gram-negative pathogens, such as Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, cause a variety of diseases in humans and animals, and a strong correlation between antibiotic use in the treatment of these diseases and antibiotic resistance development has been observed over the past half-century. This is especially apparent with the -lactam class of antibiotics and their related inactivating enzymes, the -lactamases.

Antibiotic resistance is known to occur both in the pre-antibiotic and antibiotic-era. The pre-antibiotic era constitutes the time before the introduction of sulphonamides in 1930. It is well established that resistance phenotype and the antibiotics in the pre-antibiotic era coexisted in the natural environment without facilitating the process of selection of the deadly resistant pathogens.

M. Baym et al. discussed important strategies to reverse antibiotic resistance with excellence.

First, the role of -lactamase inhibitors has been expanded to others inhibitors and -lactams other than just penicillins. Two product pairings got approval recently for use in various countries (ceftazidime-avibactam and ceftolozane-tazobactam) and others are still being studied. Avibactam is a new inhibitor that allowed covering additional resistant bacteria, including AmpC beta-lactamase and KPC-producing bacteria (

Second, although enterococci are intrinsically resistant to cephalosporins, a recent observational study supported similar effectiveness and less nephrotoxicity of ampicillin combination with ceftriaxone compared to combination with gentamicin .

Third This study was conducted after in vitro and animal models have tested combinations of double -lactams.

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