The Annals of pharmacotherapy · 2001
Linezolid for the treatment of resistant gram-positive cocci.
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Bain K T, Wittbrodt E T
Аннотация
OBJECTIVE: To provide a comprehensive review of linezolid, the first of a new class of antibiotics, the oxazolidinones. Therapeutic issues regarding the emergence of multidrug-resistant bacteria and a brief history of the oxazolidinones are also discussed.
DATA SOURCES: A MEDLINE search (1966-March 2001) was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Unpublished clinical data, adverse effects, and dosing information were abstracted from product labeling.
STUDY SELECTION: Clinical efficacy data were extracted from clinical trials, case reports, and abstracts that mentioned linezolid. Additional information concerning antibiotic resistance, the oxazolidinones, in vitro susceptibility and the pharmacokinetic profile of linezolid also was reviewed.
DATA SYNTHESIS: Linezolid exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Linezolid inhibits bacterial protein synthesis at an early step in translation and is rapidly and completely absorbed from the gastrointestinal tract following oral administration. Efficacy has been demonstrated in a number of unpublished clinical trials in adults with pneumonia, skin and skin structure infections, and vancomycin-resistant E. faecium infections. The adverse effect profile is similar to that of comparator agents (beta-lactams, clarithrornycin, vancomycin).
CONCLUSIONS: Linezolid is the first oral antimicrobial agent approved for the treatment of vancomycin-resistant enterococci. Since the oxazoildinones have a unique mechanism of action and expanded spectrum of activity against virulent and highly resistant gram positive pathogens, linezolid is a valuable alternative to currently available treatment options. Clinical trials evaluating linezolid and other oxazolidinones for antibiotic-resistant gram-positive infections, as well as comparator studies comparing linezolid with other candidate drugs, such as quinupristin/dalfopristin and choramphenicol, will further define the role of linezolid.
DATA SOURCES: A MEDLINE search (1966-March 2001) was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Unpublished clinical data, adverse effects, and dosing information were abstracted from product labeling.
STUDY SELECTION: Clinical efficacy data were extracted from clinical trials, case reports, and abstracts that mentioned linezolid. Additional information concerning antibiotic resistance, the oxazolidinones, in vitro susceptibility and the pharmacokinetic profile of linezolid also was reviewed.
DATA SYNTHESIS: Linezolid exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Linezolid inhibits bacterial protein synthesis at an early step in translation and is rapidly and completely absorbed from the gastrointestinal tract following oral administration. Efficacy has been demonstrated in a number of unpublished clinical trials in adults with pneumonia, skin and skin structure infections, and vancomycin-resistant E. faecium infections. The adverse effect profile is similar to that of comparator agents (beta-lactams, clarithrornycin, vancomycin).
CONCLUSIONS: Linezolid is the first oral antimicrobial agent approved for the treatment of vancomycin-resistant enterococci. Since the oxazoildinones have a unique mechanism of action and expanded spectrum of activity against virulent and highly resistant gram positive pathogens, linezolid is a valuable alternative to currently available treatment options. Clinical trials evaluating linezolid and other oxazolidinones for antibiotic-resistant gram-positive infections, as well as comparator studies comparing linezolid with other candidate drugs, such as quinupristin/dalfopristin and choramphenicol, will further define the role of linezolid.