New Drugs Targeting Antibiotic-Resistant Bacteria: Recent Advances

Despite the undeniable benefits of antibiotics, the emergence of resistance presents a formidable challenge. This section examines the evolution of MultidrugResistant Organisms (MDROs), highlighting the complexities of systematic reporting and advocating for comprehensive surveillance to understand the true extent of the epidemic.

Initial successes of antibiotics, exemplified by penicillin, were short-lived as resistance swiftly emerged, marking the onset of the antibiotic resistance era. The current scenario reveals elevated resistance rates, particularly in low- and middle-income countries.

Medical concerns and reports highlight the ongoing apprehensions within the medical community regarding multidrug resistance, which dates back to the 1960s. Recent reports emphasize a global crisis of antibiotic scarcity and the rapid development of resistance. Livestock, pets, and other animals, as well as water and vegetables, are also contributing to the MDRO epidemic. The involvement of environmental animals and vegetables emphasizes the need for active epidemiological surveillance across all these sectors to prevent the transmission of MDRO, reinforcing the importance of environmental sanitation.

In conclusion, the origin and extent of the MDRO epidemic remain challenging to determine despite recent global surveillance efforts. The impact on health indicates a high association with mortality. There is a need for a One Health approach, addressing MDRO comprehensively in humans, animals, soil, water, and manure. The focus is on infection prevention and control, as well as optimizing antibiotic use to break the resistance acquisition and transmission chain.

Bacteriophages are the most abundant biological entities on the planet and are specific viruses that target only bacteria. The use of these viruses to combat bacterial infections is known as phage therapy, a concept that was implemented in the early 20th century. However, its application in Western medicine was halted following the discovery and use of antibiotics. Still, due to the alarming increase in antibiotic resistance we are experiencing, phage therapy is gaining acceptance in Western countries, and several successful cases have been documented. In this chapter, we discuss various aspects of phage therapy, from bacteriophage isolation and characterization to the development of phage-suitable formulations and their administration for treating human infections. We also examine successful cases of phage therapy in treating life-threatening infections that are untreatable with current antibiotics, highlighting the advantages and limitations of phage therapy compared to traditional antimicrobials. 

The global health crisis caused by antimicrobial resistance presents a challenge that demands a rapid response. For decades, the development of antibiotics has significantly improved our quality of life. Shortly after their discovery, diseases and pests that had caused numerous deaths were controlled. Similarly, antibiotics facilitated advancements in medical and surgical practices, as well as enhanced food supply through agricultural applications. The marketed antibiotics were developed based on research into natural products of microbial origin. Therefore, this chapter examines various ongoing efforts and strategies to discover new antibacterials from natural products. It explores both traditional methods and innovative techniques for managing non-culturable microorganisms. The results inspire hope for a second golden age for these molecules. However, we must exercise greater responsibility in their use.

Multidrug resistance is a global and severe public health concern; according to data from Jim O´Neil, in 2050, deaths could rise to 10 million. Each time, clinical options are decreasing. The outlook is discouraging, not considering the increased resistance during the COVID-19 pandemic.

The last line of defense for clinicians is the use of carbapenems, and developing new clinical pharmacological strategies involves the use of site-specific inhibitors. Identifying the enzymes that degrade these types of antimicrobials is crucial. It is the key to reducing the selection pressure and ensuring their proper use. The half-life of a molecule is dictated by its prescription, and this is where the clinical microbiology laboratory comes in. It is not just a place for testing; it serves as the guiding axis for the correct, adequate, and rational administration of drugs. In this chapter, we will delve into the importance of carbapenemases-mediated resistance and its classification, impact, and detection strategies. 

The Centers for Disease Control and Prevention (CDC-USA) has categorized bacterial infections as urgent, serious, and concerning threats. In this chapter, we will discuss the antibiotics suggested by the CDC-USA to combat the urgent threats caused by drug-resistant bacteria, including carbapenem-resistant Acinetobacter and Enterobacteriaceae, Candida auris, Clostridioides difficile, and Drug-resistant Neisseria gonorrhoeae.

The chapter reviews the efficacy of carbapenem antibiotics when combined with βlactamase inhibitors. Additionally, it discusses using quorum-sensing inhibitors to prevent virulence factors, focusing on halogen furanone-type compounds. Interestingly, such inhibitors are effective in vitro, but none are currently being evaluated in clinical settings. Finally, some syntheses of nanoparticles to counteract drug-resistant bacteria are reported. Nanoparticles made from metals, especially silver, and those synthesized using biodegradable polymeric materials have shown promising results in cytotoxic activity. However, further studies are needed to determine their effectiveness and toxicity.