Advances in novel antibiotics to treat multidrug-resistant gram-negative bacterial infections

Abstract

Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately.

Discovery of Mycobacterium tuberculosis Rv3364c-Derived Small Molecules as Potential Therapeutic Agents to Target SNX9 for Sepsis

“…That is, it selectively kills or inhibits the growth of microbial targets with minimal or no harm to the host. Most antibacterial drugs currently used in clinical practice are antibacterial because prokaryotic cells provide a variety of unique targets for selective toxicity. , …”

“…For example, polymyxins (B or E) interact with lipopolysaccharide in the outer membrane of Gram-negative bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membrane. However, Lipopeptide (daptomycin) inserts into the cytoplasmic membrane of Gram-positive bacteria, disrupting the membrane and killing the cells. , The rapid efflux of accumulated amino acids, followed by ATP depletion, followed by decreased membrane potential suggested that DATPT abolished the membrane potential and ion gradient across the cytoplasmic membrane. , To determine the effect of DATPT on intracellular ATP concentration, the total and external ATP levels were measured after 20 h of treatment with DATPT during intact bacterial culture, and the internal ATP levels were calculated by subtracting the external ATP from total ATP. Notably, increasing DATPT concentrations decreased the ATP levels in bacterial cells and increased external ATP concentrations, suggesting that the intracellular hydrolysis of ATP was primarily responsible for the decrease in the internal ATP in bacterial cells (Figure C).…”

“…Most antibacterial drugs currently used in clinical practice are antibacterial because prokaryotic cells provide a variety of unique targets for selective toxicity. 32,33 The main biological target of antibacterial drugs is to inhibit cell wall biosynthesis, protein synthesis, membrane function, nucleic acid synthesis, and metabolic pathways. A small group of antibacterials target the bacterial membrane as their mode of action.…”

“…However, Lipopeptide (daptomycin) inserts into the cytoplasmic membrane of Gram-positive bacteria, disrupting the membrane and killing the cells. 33,34 The rapid efflux of accumulated amino acids, followed by ATP depletion, followed by decreased membrane potential suggested that DATPT abolished the membrane potential and ion gradient across the cytoplasmic membrane. 34,35 To determine the effect of DATPT on intracellular ATP concentration, the total and external ATP levels were measured after 20 h of treatment with DATPT during intact bacterial culture, and the internal ATP levels were calculated by subtracting the external ATP from total ATP.…”

Biomineralized Cascade Enzyme-Encapsulated ZIF-8 Nanoparticles Combined with Antisense Oligonucleotides for Drug-Resistant Bacteria Treatment

“…While preventing and controlling the epidemic, the prevention and treatment of drug-resistant bacterial infections are even more indispensable. − According to the test reports of the China Antimicrobial Resistance Surveillance System (CARSS), in 2020, Gram-positive bacteria and Gram-negative bacteria accounted for 28.1 and 71.9% of the total clinical isolates, respectively. The detection rate of methicillin-resistant strains in Staphylococcus aureus was as high as 31.0%. − Bacteria seriously invade our surrounding living environment, and the irresistible use of antibiotics continuously accelerates the development of resistant strains, making bacterial infections become worldwide diseases with high morbidity and mortality. , Aiming to solve the global health problem of bacterial infections, the task of exploring and developing emerging and alternative methods for effective treatment of bacterial infections is imminent.…”