Antibiotics, drugs used to treat and prevent bacterial infections, have transformed medicine and enabled our contemporary lifestyle. Initially developed in the 1900s, antibiotics were once seen as a definitive victory against microorganisms. However, it soon became apparent that microorganisms could become resistant to any administered drug. Most pathogenic microorganisms are capable of developing resistance to some antimicrobial treatments. Simply put, when germs do not respond to the drugs designed to kill them, previously treatable infections can become fatal. The term “antimicrobial resistance” encompasses all types of microbes, including bacteria, fungi, and viruses, that cause infections.
Antimicrobial Resistance (AMR) results from bacteria, viruses, fungi, and parasites evolving over time to become resistant to antibiotics. When we discuss antibiotic resistance, we refer to bacteria, not humans, becoming resistant to these drugs. This resistance complicates infections, increasing the risk of disease spread, serious illness, and death.
Drug-resistant illnesses like malaria, cholera, and tuberculosis are increasingly common in India, and the emergence of novel multi-drug resistant organisms adds further challenges to diagnosis and treatment. A lack of knowledge about infectious diseases and limited access to healthcare can discourage timely medical intervention.
The global rise of “superbugs,” or multi- and pan resistant bacteria causing diseases resistant to current treatments, is especially alarming. These bacteria impact every level of society, but healthcare systems are particularly hard hit. The discovery of new antibiotics is rare and infrequent, with most current antibiotic classes discovered in the mid-to late 20th century. Drugs to combat resistant bacteria are scarce, and resistance can develop in multiple drug-resistant bacteria simultaneously.
The problem of antibiotic resistance in Gram Negative Bacteria (GNB) presents a daily challenge in Intensive Care Units (ICUs). GNB are responsible for 20-30% of bloodstream infections related to catheter use, 45-70% of ventilator-associated pneumonia (VAP), and often cause additional ICU acquired sepsis, such as surgical site or urinary tract infections (UTIs).
Each ICU has a unique bacterial ecology that can change based on factors like patient enrollment, antibiotic use policies, and sporadic outbreaks. The Wellcome Trust predicts that by 2050, resistant infections will account for 10 million deaths annually, becoming the leading cause of death worldwide. Given the scarcity of novel antimicrobial agents in the drug development pipeline, we face challenges potentially greater than those posed by HIV, TB, and malaria.
Mechanisms of Resistance to Antibacterial Agents
Bacteria can develop resistance through de novo mutation, acquiring resistance genes from other species, or natural resistance to multiple antimicrobial drugs. A bacterium with acquired resistance genes might produce enzymes that break down the drugs, express efflux systems preventing the drug from reaching its intracellular target, alter the drug’s target site, or create a different metabolic pathway that bypasses the drug’s effects. Antibiotics typically cause cell death and growth retardation by targeting and inhibiting vital biological processes.
However, bacteria exposed to drugs at doses lower than the minimum bactericidal concentration (MBC) can develop resistance through natural selection for resistance-conferring mutations. These genetic changes can result from alterations in the bacterial chromosome or the uptake of a plasmid carrying a resistance gene.
– Dr Subramanian S. Iyer
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