Related Experiment Videos
Perspectives on the development of new antimicrobial agents for resistant gram-positive pathogens
1Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. ronald-jones@uiowa.edu
Abstract:
There is great public and professional concern related to antimicrobial resistance, especially among Gram-positive pathogens associated with high morbidity and mortality. Penicillin-nonsusceptible Streptococcus pneumoniae, glycopeptide resistant enterococci, and oxacillin-resistant (MRSA) or vancomycin-intermediate (VISA) Staphylococcus aureus isolates continue to escalate in occurrence leading to the widespread use of empiric combination regimens. Newer, often novel, agents seem necessary to combat these pathogens. Among these, quinupristin/dalfopristin (Synercid), evernimicin or SCH 27899 (Ziracin), and linezolid (Zyvax) have the highest potency, widest spectrum, and most clinical experience. Among the quinolones (gatifloxacin, gemifloxacin, moxifloxacin), gatifloxacin is closest to clinical use and appears safe based on initial trial reports. Several broad-spectrum beta-lactams ("fourth-generation" cephalosporins, carbapenems) are expected to be used with increasing frequency as a result of the emerging high rates of specific beta-lactamases that compromise the use of ceftriaxone, ceftazidime, and many beta-lactamase inhibition/ penicillin combinations. Among these agents, cefepime and meropenem are the most potent and broadest in clinical application in their respective classes. Physicians must stay informed about drug development and antimicrobial resistance by using results from local surveillance programs. When these data are unavailable, physicians should consider the use of national or global monitoring systems (SENTRY) to direct empiric antimicrobial selection.
Insights
Antimicrobial resistance in Gram-positive pathogens is a growing concern. Newer agents like quinupristin/dalfopristin, linezolid, and advanced cephalosporins/carbapenems are crucial for effective treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising antimicrobial resistance in Gram-positive pathogens (e.g., MRSA, VISA, penicillin-nonsusceptible Streptococcus pneumoniae, vancomycin-resistant enterococci) poses significant clinical challenges.
- Increasing morbidity and mortality associated with these resistant infections necessitate novel therapeutic strategies.
- Widespread use of empiric combination regimens highlights the urgent need for new antimicrobial agents.
Purpose of the Study:
- To review emerging antimicrobial agents and their potential role in combating resistant Gram-positive pathogens.
- To discuss the clinical utility and spectrum of activity of novel antibiotics.
- To emphasize the importance of informed antimicrobial selection based on resistance surveillance data.
Main Methods:
- Review of current literature on antimicrobial resistance trends.
- Evaluation of newer antimicrobial agents, including quinupristin/dalfopristin, evernimicin, linezolid, advanced quinolones, and broad-spectrum beta-lactams.
- Discussion of the role of surveillance programs in guiding empiric therapy.
Main Results:
- Quinupristin/dalfopristin, evernimicin, and linezolid show high potency and broad spectrum against resistant Gram-positive pathogens.
- Advanced quinolones, such as gatifloxacin, demonstrate safety and efficacy.
- Broad-spectrum beta-lactams, including cefepime and meropenem, offer potent options against emerging beta-lactamase threats.
Conclusions:
- Novel antimicrobial agents are essential to address the escalating threat of resistant Gram-positive infections.
- Physicians must utilize local, national, and global surveillance data (e.g., SENTRY program) to guide empiric antimicrobial selection.
- Staying informed about drug development and resistance patterns is critical for effective patient management.