Designing Drug Combinations to Prevent Antibiotic Resistance

Abstract

Antibiotics are immense weapon that fight microbes. For decades, several varieties of antibiotics have not only been used for clinical purposes but practiced across other industries like agriculture and animal husbandry. The regular practice in antibacterial drug development has been to rapidly make an effort to find ever-more stable and broad-spectrum alternative for a particular antibiotic, once a drug resistance for that antibiotic is detected. We are now facing bacterial resistance toward our clinically relevant antibiotics of such a magnitude that the conversation for antimicrobial drug development ought to include effective new antibiotics with alternative mechanisms of action. Microbial resistance to antibiotics is a world-wide problem in human and veterinary medicine. It is generally accepted that the main risk factor for the increase in the antibiotic resistance is an extensive use of antibiotics. This has lead to the emergence and dissemination of resistant bacteria and resistance genes in animals and humans. The aim of this review is to explore the origin, development, and the current state of antibiotic resistance, regulation, and challenges by examining available literature. We found that antibiotic resistance is increasing at an alarming rate. A growing list of infections i.e., pneumonia, tuberculosis, and gonorrhea are becoming harder and at times impossible to treat while antibiotics are becoming less effective. Antibiotic-resistant infections correlate with the level of antibiotic consumption. Non-judicial use of antibiotics is mostly responsible for making the microbes resistant. The antibiotic treatment repertoire for existing or emerging hard-to-treat multidrug-resistant bacterial infections is limited, resulting in high morbidity and mortality report. This review article reiterates the optimal use of antimicrobial medicines in human and animal health to reduce antibiotic resistance. Evidence from the literature suggests that the knowledge regarding antibiotic resistance in the population is still scarce. Therefore, the need of educating patients and the public is essential to fight against the antimicrobial resistance battle. A primary characteristic of antibiotics is that they lose their effectiveness over time. In the last twenty years, the number of antibiotic classes and analogues in development has not kept pace with antibiotic resistance. Appropriate use of existing classes of antibiotics could improve the lifespan of these drugs. The side effects of antibiotic resistance include reduced patient outcomes and increasingly potent disease states. New government task forces have been developed to increase the level of research and federal involvement into this growing public health problem.

Single-Fluorescence ATP Sensor Based on Fluorescence Resonance Energy Transfer Reveals Role of Antibiotic-Induced ATP Perturbation in Mycobacterial Killing

“…Considering the close relationship between mycobacterial ATP fluctuations and antibiotic-induced cell death, cellular ATP levels might be a good indicator with which to develop potent drug combinations for the treatment of TB. Drug combination is an effective strategy for the treatment of clinical infections, especially for preventing antibiotic resistance ( 48 ). Clinical trials and regression analysis are needed for drug combination design, where broth-based checkerboard assays and time-kill experiments are the gold standards.…”

Refugia and the evolutionary epidemiology of drug resistance

“…As a consequence, attention is turning to prudent use of drugs in management strategies designed to slow the development of drug resistance. These include diagnosing and treating only infected (or suspected infected) individuals [6], using dose control to limit the rate of drug resistance emergence within-hosts [14], personalized medicine [15], drug combinations [16] and refugia [10].…”