Whether introduced through bomb shrapnel or surgical tools, the persistent superbug in a woman defied years of antibiotic treatment. The survivor of a terrorist attack was ultimately liberated from the drug-resistant Klebsiella pneumoniae through a novel experimental therapy.
Growing Problem in Antibiotic Resistance
Antibiotics function by either directly killing bacteria or impeding their growth, allowing the immune system to eliminate the remaining bacteria. These drugs operate through various mechanisms, such as hindering cell wall formation or DNA replication. Broad-spectrum antibiotics target common molecular targets and can affect both gram-positive and gram-negative bacteria, leading to the evolution of defensive mechanisms against them.
Bacteria acquire these defenses through random DNA mutations and horizontal gene transfer, sharing "resistance genes" with other bacteria. This rapid gene transfer can disseminate mutations to diverse bacterial populations in the body and the environment. The widespread misuse of antibiotics in healthcare and agriculture has created opportunities for bacteria to develop resistance, posing a significant risk of once-treatable infections becoming life-threatening.
The prevalence of drug-resistant bacterial infections poses a growing global health threat, with approximately 1.27 million direct deaths and 3.68 million contributing deaths in 2019. In the United States, drug-resistant bacteria and fungi result in an estimated 2.8 million infections and 35,000 deaths annually.
Furthermore, seven of the 18 bacteria monitored by the Centers for Disease Control and Prevention (CDC) are becoming more resistant to crucial antibiotics, while drug companies have been slow to develop new antibiotics. Fewer than 30 antibiotics in development target "priority" bacteria defined by the World Health Organization (WHO), and most remain susceptible to resistance.
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Finding Innovative Approaches Against Antibiotic Resistance
In response to the worsening antibiotic resistance, some scientists are exploring alternatives to traditional antibiotics, including bacteriophages, CRISPR technology, and antimicrobial molecules, aiming to combat superbugs without exacerbating resistance.
Phage therapy, which uses bacteriophages to combat bacteria, offers a potential alternative to antibiotics. Unlike antibiotics, which have led to widespread resistance due to misuse and overuse, phages have narrower targets, allowing scientists to select combinations that impose a cost on bacteria's evolution, such as reduced virulence or increased vulnerability to antibiotics.
Meanwhile, CRISPR technology was originally derived from bacteria's immune system and employs molecular scissors (Cas proteins) and DNA snippets to precisely target and edit DNA sequences. Researchers are exploring the use of CRISPR-Cas in phages to selectively attack and kill specific bacterial cells, offering a sequence-specific approach for treating infections.
Antibiotic stewardship is another critical strategy to slow the rise of antibiotic-resistant bacteria by promoting responsible antibiotic use, curbing misuse, and tracking adherence to prescribing principles.
It focuses on setting guidelines for antibiotic prescription and use, particularly in healthcare settings like hospitals and nursing homes. The goal is to discourage inappropriate antibiotic use, such as prescribing antibiotics for viral infections or opting for broad-spectrum antibiotics when narrow-spectrum drugs are effective.
Broad-spectrum antibiotics are of particular concern because they can induce resistance in a wide range of bacteria, which can then share resistance mechanisms among each other.
Addressing antibiotic resistance requires both the development of alternative treatments and responsible antibiotic stewardship practices to safeguard the effectiveness of these essential drugs.
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