Current Concepts in Antimicrobial Therapy Against Select Gram-Positive Organisms: Methicillin-ResistantStaphylococcus aureus, Penicillin-Resistant Pneumococci, and Vancomycin-Resistant Enterococci

Abstract

Gram-positive bacteria cause a broad spectrum of disease in immunocompetent and immunocompromised hosts. Despite increasing knowledge about resistance transmission patterns and new antibiotics, these organisms continue to cause significant morbidity and mortality, especially in the health care setting. Methicillin-resistant Staphylococcus aureus poses major problems worldwide as a cause of nosocomial infection and has emerged as a cause of community-acquired infections. This change in epidemiology affects choices of empirical antibiotics for skin and skin-structure infections and community-acquired pneumonia in many settings. Throughout the world, the treatment of community-acquired pneumonia and other respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae has been complicated by resistance to β-lactam and macrolide antibacterial drugs. Vancomycin-resistant enterococci are a major cause of infection in the hospital setting and remain resistant to treatment with most standard antibiotics. Treatment of diseases caused by resistant gram-positive bacteria requires appropriate use of available antibiotics and stewardship to prolong their effectiveness. In addition, appropriate and aggressive infection control efforts are vital to help prevent the spread of resistant pathogens.

Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection

“…As a result, resistance to even the most recently developed agents is emerging at an alarming pace (17,18). The impact of this trend is of special concern in light of high rates of mortality associated with invasive MRSA infection (e.g., 15-40% in bacteremia or endocarditis), even with the most recently developed antistaphylococcal therapeutics (19,20).…”

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“…Nowadays, vancomycin is used as drug of choice for treating MRSA, but the emergence of vancomycin intermediate-sensitive S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) has limited even this therapeutic route [2]. In these more severe cases, the drugs of choice are quinupristin/ dalfopristin, minocycline, daptomycin and linezolid [23][24][25][26][27][28]. Taken together, these issues highlight the importance of searching new drugs to fight such pathogens.…”

Current Trends in Streptococcus pneumoniae Infections and Their Treatment

“…Linezolid is a synthetic oxazolidinone active in vitro against resistant Gram-positive bacteria, including MRSA, vancomycin-resistant enterococcus, and MDR S. pneumoniae [100]. Initially approved for clinical use by the FDA in 2000, linezolid is bacteriostatic and inhibits bacterial protein synthesis by binding to domain V of the 23S ribosomal RNA of the 50S subunit [101].…”

“…New antimicrobial agents available for treatment of resistant Gram-positive infections include daptomycin, tigecycline, and telavancin [100]. Ceftaroline is a novel fifth-generation cephalosporin with broad-spectrum of activity against both Gram-positive and -negative pathogens including MRSA and resistant pneumococci [100]. Newer agents in ketolides (a subclass of macrolides) under development include telithromycin, cethromycin, and solithromycin [102 •• ].…”