Antibiotics have saved millions of lives since their discovery. But now, it’s time to save antibiotics. Sir Alexander Fleming had warned about the indiscriminate use, which can lead to antibiotic resistance. For many decades, clinicians were fortunate as newer antibiotics were available if resistance was developed to the previous ones. The development of resistance to existing antibacterial agents became a regular phenomenon as if bacteria were programmed to develop resistance. In case of some nosocomial infections, the clinicians are left with no available antibiotic choice. The era of antibiotics appeared to be ending. The discovery of new antibacterial agents lagged and could not matchup with the development of antimicrobial resistance. The WHO had to declare the “postantibiotic era”. Desperate actions are needed to overcome this insurmountable crisis. There is a dire need to reverse the antimicrobial resistance.1 Antimicrobial resistance is a more serious threat, especially in hospital-acquired infections than in community-acquired infections. The bacteria inhabiting the hospital environment are constantly under selection pressure of antibacterial agents. With the advent of newer techniques, such as chemotherapy, organ transplantation, and hematopoietic stem cell transplant, the life span is increased. Paradoxically, it has led to the increased population of immunocompromised patients. These patients are incapable of clearing the infection on their own and require prolonged antibiotic treatment. This was one of the reasons for the development of drug resistance. The bacteria adopt various mechanisms to acquire drug resistance. Most hospital bacterial strains develop resistance by chromosomal mutation or by the acquisition of genes from other bacteria in the form of extrachromosomal mobile genetic elements. The acquired genes bring about mutation in drug-binding sites, secretion of enzymes to render antibiotics ineffective (β-lactamases), and change in cell permeability or efflux pumps to pump the drug outside the bacterial cell. Reversing this acquired antimicrobial resistance (AMR) is a huge challenge. What can we do to reverse AMR? Various strategies to combat antibiotic resistance exist. Many of them are in practice. We need to find newer strategies. Hospital infection control Frequent hand washing, mopping, and surface cleaning are usual but effective ways to reduce nosocomial infections as well as the use of antibiotics. Following proper hygienic hospital interventions, such as different types of scopies, operative procedures, ventilator use, and catheterization, has a definitive role in the reduction of hospital-acquired infections.2 Restricting the use of higher antibiotics Employing antibiotic stewardship to reduce unnecessary antibiotic usage. The simple way to reverse the AMR is to reduce the use of higher antibiotics in hospitals. Although it sounds like a good idea, practically, it is not easy to apply, as most of the patients in the intensive care units (ICUs) are very sick and debilitated. Their survival, most of the time, is dependent on the use of higher antibiotics.3 Reducing selection pressure Research has proved that when not under antibiotic pressure or if the bacteria are not exposed to antibiotics for a long time, they tend to lose their plasmids. The studies have shown that when not under selection pressure, the bacteria tend to lose the plasmids conferring antibiotic resistance. Not exposing the nosocomial bacterial strains for a long time may result in increased susceptibility. The practical application of this is very difficult as the flow of new vulnerable patients in ICUs is constant.4 Improving vaccination Individual vaccination can prevent many infections. There are many zoonotic infections, and transmission of this infection to humans can be prevented by vaccination of animals, for example, brucellosis.5 Developing new antibiotics For years, researchers have been employing molecules that bind to specific targets to hinder the synthesis of cell walls, proteins, or multiplication pathways of bacterial cells. Most of these pathways, by now, are employed, and research is needed to find other ways to hinder the process of bacterial growth. Developing faster point-of-care tests This helps in early detection of bacterial infection, timely targeted antibiotic therapy, and reduction in usage of empiric broad-spectrum antibiotic use. Cyclical use of antibiotics If a particular broad spectrum antibiotic is used to treat infections empirically restricting the use of other broad spectrum antibiotics. This may help in reducing selection pressure on the hospital bacteria of other antibiotics. Cyclical use of antibiotics in hospitals has been shown to decrease the resistance. For example: using cefoperazone–sulbactam and piperacillin–tazobactam cyclically.6 What Further Research Is Needed? There are newer antibiotics in the pipeline. New antibiotics take a long time for their clinical trials and approval by authorities. Bacteria are also known to develop resistance to newer antibiotics rapidly, resulting in the research not yielding for the investors. Identifying the mechanisms of resistance and breaking them With molecular and genetic techniques, researchers can decipher the molecular mechanisms of drug resistance. Beta-lactamase inhibitors Bacteria secrete numerous Beta-lactamase enzymes (that render the B lactam antibiotics useless by breaking the Beta-lactam ring.). These enzymes have been identified, and chemicals have been developed to hydrolyze these enzymes. These beta-lactamase inhibitors are used in combination with beta-lactam antibiotics effectively. Developing efflux pump inhibitors Efflux pump in bacterial cell throws the antibiotic out of the bacterial cell and reduce their effects. Efflux pumps are now considered interesting targets by researchers and new efflux pump inhibitors are under study.7 Using molecules that will disrupt the cell wall integrity and make way for the antibiotic molecules to the binding sites. Development of alternative methods to treat infections Bacteriophage viruses have been known for a long time. The therapeutic use of bacteriophage is now employed to treat infections with recalcitrant infective strains. They, in some instances, have proved very promising.8 Use of natural product Some plant and animal products have shown antibacterial activity. More experimental studies are needed to establish pharmacokinetics and pharmacodynamics of these products to establish efficacy before implementation of these products for clinical use. Molecular approach Development of chemicals that have antivirulence factor activity Newer strategies are under development to use chemicals that have activity against bacterial virulence factors such as bacterial adhesion, inhibiting toxins, modulating virulence gene expression, neutralizing pathogens, inhibiting quorum sensing, targeting type III secretion systems.9 All these chemicals may be used in combination with the existing antibacterial agents. This may involve individual pathogen treatment. Newly developed CRISPR-Cas technologies are under study for disabling the resistance genes by removing them from the bacterial cells.10 Finally, the government should encourage research for the development of newer antibacterial agents. The research can be enhanced by proper funding for the proper projects. It is high time for the community to give due respect to the researchers to promote the research activity. Much can be done to avert this imminent pandemic of MDR pathogens.
Anant Marathe (Wed,) studied this question.