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Novel agents for resistant Gram-positive infections--a review
Jacob Strahilevitz1, Ethan Rubinstein
1The Infectious Diseases Unit, Sheba Medical Center, Sackler School of Medicine, Tel-Hashomer, Israel.
Abstract:
Gram-positive infections have increased in recent years, particularly those that are of nosocomial origin, leading to a broad use of agents with activity against these pathogens. Concomitantly, antimicrobial resistance of these pathogens also became widespread. Among the most common Gram-positive resistant pathogens are: Streptococcus pneumoniae, resistant to penicillin and macrolides, methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediately-resistant S. aureus (GISA), methicillin-resistant S. epidermidis, glycopeptide-resistant enterococci and vancomycin-resistant enterococci (VRE). The response of the pharmaceutical industry to this challenge was the development of new antibiotics active against these pathogens. Among these antibiotics, this review will focus on: linezolid, an oxazolidinone; GAR-936, a tetracycline derivative; daptomycin, a lipopeptide; and ortivancin (LY-333328), a glycopeptide related to vancomycin. Except for linezolid, which has been recently launched in many countries, all other agents referred to in this review are still at various developmental stages. It is hoped that in the near future most of these agents will be approved and thus the grim outlook of patients infected with resistant Gram-positive bacteria may improve.
Insights
Rising Gram-positive infections and antimicrobial resistance necessitate new treatments. This review highlights novel antibiotics like linezolid, daptomycin, and others to combat resistant pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Increasing incidence of Gram-positive bacterial infections, especially nosocomial ones.
- Widespread antimicrobial resistance in key pathogens like MRSA, VRE, and penicillin-resistant Streptococcus pneumoniae.
- Growing need for effective therapeutic agents against multidrug-resistant Gram-positive bacteria.
Purpose of the Study:
- To review emerging antibiotics developed to combat resistant Gram-positive pathogens.
- To provide an overview of novel agents including linezolid, GAR-936, daptomycin, and ortivancin.
- To assess the current development status and potential impact of these new antibiotics.
Main Methods:
- Literature review of recent scientific publications and clinical trial data.
- Focus on antibiotics targeting resistant Gram-positive bacteria.
- Analysis of drug classes: oxazolidinones, tetracycline derivatives, lipopeptides, and glycopeptides.
Main Results:
- Linezolid is a recently launched oxazolidinone with activity against resistant Gram-positive bacteria.
- GAR-936 (tetracycline derivative), daptomycin (lipopeptide), and ortivancin (glycopeptide) are in various developmental stages.
- These novel agents represent promising therapeutic options for challenging Gram-positive infections.
Conclusions:
- New antibiotics are crucial for managing the increasing threat of resistant Gram-positive infections.
- Linezolid, daptomycin, GAR-936, and ortivancin show potential to improve treatment outcomes.
- Further development and approval of these agents are anticipated to address the limitations of current therapies.