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Published on: April 18, 2019
Multidrug-Resistant Enterococcal Infections: New Compounds, Novel Antimicrobial Therapies?
Roel M van Harten1, Rob J L Willems1, Nathaniel I Martin2
1Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Abstract:
Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting.
Insights
Antibiotic-resistant Enterococcus infections are a growing threat. Novel compounds targeting Gram-positive bacteria show promise for future treatments against these difficult-to-treat pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic-resistant bacterial infections, particularly from Enterococcus species, pose a significant global health challenge.
- Enterococcus faecium and Enterococcus faecalis are opportunistic pathogens causing nosocomial infections that are increasingly difficult to treat due to widespread antibiotic resistance.
- The rising prevalence of these infections impacts patient morbidity, mortality, and healthcare expenses worldwide.
Purpose of the Study:
- To review novel antimicrobial compounds developed against Gram-positive bacteria, focusing on their potential to treat Enterococcus infections.
- To analyze the mechanisms of action and efficacy of these new agents.
- To project the future clinical utility of promising anti-enterococcal compounds.
Main Methods:
- Literature review of recent discoveries in antimicrobial compound classes targeting Gram-positive bacteria.
- Analysis of novel agents including teixobactin, nisin-derived lipopeptides, vancomycin analogues, sortase inhibitors, alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors, oxazolidinones, and tarocins.
- Evaluation of compound targets (e.g., lipid II, lipid III, sortase enzyme, ribosome, LtaS, teichoic acid biosynthesis) and their efficacy in preclinical animal models.
Main Results:
- Several novel antimicrobial classes demonstrate potential against Enterococcus species.
- Compounds target diverse essential bacterial pathways, including cell wall synthesis, protein synthesis, and cell wall precursor biosynthesis.
- Promising agents show efficacy in animal models, indicating potential for clinical application.
Conclusions:
- Novel antimicrobial agents targeting specific pathways in Gram-positive bacteria represent a promising strategy against antibiotic-resistant Enterococcus infections.
- Understanding the mechanisms of action and preclinical efficacy is crucial for advancing these compounds towards clinical use.
- These new drug classes offer hope for improved treatment options for difficult-to-treat enterococcal infections in the future.
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