Clinical Pharmacodynamics of Linezolid in Seriously Ill Patients Treated in a Compassionate Use Programme

Abstract

Higher success rates for linezolid may occur at AUC/MIC values of 80-120 for bacteraemia, LRTI and SSSI. Chance of success in bacteraemia, LRTI and SSSI also appear to be higher when concentrations remain above the MIC for the entire dosing interval.

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

“…It is a valid therapeutic alternative to glycopeptides against multiresistant Gram-positive strains such as staphylococci, streptococci and enterococci, which are particularly frequent in the ICU [37]. Linezolid is a time-dependent antimicrobial agent with a persistent antibiotic effect and the PK/PD indices T >MIC and AUC/MIC are important determinants of its efficacy in vitro and in vivo [38,39]. In several animal infection models, a T >MIC >40% significantly M a n u s c r i p t enhanced bacterial killing of pneumococci, and AUC/MIC ratios of 48-147 were necessary for a bacteriostatic effect [38,38,40].…”

“…Linezolid is a time-dependent antimicrobial agent with a persistent antibiotic effect and the PK/PD indices T >MIC and AUC/MIC are important determinants of its efficacy in vitro and in vivo [38,39]. In several animal infection models, a T >MIC >40% significantly M a n u s c r i p t enhanced bacterial killing of pneumococci, and AUC/MIC ratios of 48-147 were necessary for a bacteriostatic effect [38,38,40]. Linezolid serum levels with T >MIC >50% for pathogens with MICs of 2-4 mg/L can be obtained in healthy volunteers by administration of 600 mg every 12 h [41].…”

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

“…52 In two controlled trials of hospital-acquired pneumonia, a trend was seen for linezolid superiority over vancomycin. 53,54 There is little data (mainly based on observational studies), on the utility of linezolid for either bacteremia, 55 or osteomyelitis. 56,57 Based on a rabbit model, linezolid does not have sufficient CSF penetration and should not be recommended for pneumococcal meningitis.…”

“…Linezolid has been evaluated for Gram-positive bacteria. 55,88,89 Among 108 bacteremic patients receiving linezolid, eradication was seen in 91% and clinical cure was seen in 94% of the episodes. 55 On the other hand, linezolid is still not approved for catheter-related becteremia and endocarditis.…”

“…55,88,89 Among 108 bacteremic patients receiving linezolid, eradication was seen in 91% and clinical cure was seen in 94% of the episodes. 55 On the other hand, linezolid is still not approved for catheter-related becteremia and endocarditis. A randomized study of 726 patients with catheter-related bacteremia received linezolid or vancomycin; an excess number of deaths were seen for patients receiving linezolid due mainly to Gram-negative rods implicated in these infections.…”