Results of the Surveillance of Tedizolid Activity and Resistance Program: in vitro susceptibility of Gram-positive pathogens collected in 2011 and 2012 from the United States and Europe

• Published in: Diagnostic microbiology and infectious disease 2015-02, Vol.81 (2), p.112-118
• Main Authors: Sahm, Daniel F, Deane, Jennifer, Bien, Paul A, Locke, Jeffrey B, Zuill, Douglas E, Shaw, Karen J, Bartizal, Ken F
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Anti-Bacterial Agents - pharmacology; cfr; Epidemiological Monitoring; Europe - epidemiology; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - isolation & purification; Gram-Positive Bacterial Infections - epidemiology; Gram-Positive Bacterial Infections - microbiology; Humans; Infectious Disease; Internal Medicine; Linezolid; Microbial Sensitivity Tests; Mutation; Organophosphates - pharmacology; Oxazoles - pharmacology; Oxazolidinone; Oxazolidinones - pharmacology; Ribosomal Proteins - genetics; RNA, Ribosomal, 23S - genetics; Surveillance; Tedizolid; United States - epidemiology
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2014.08.011

Abstract The in vitro activity and spectrum of tedizolid and comparators were analyzed against 6884 Gram-positive clinical isolates collected from multiple US and European sites as part of the Surveillance of Tedizolid Activity and Resistance Program in 2011 and 2012. Organisms included 4499 Staphylococcus aureus , 537 coagulase-negative staphylococci (CoNS), 873 enterococci, and 975 β-hemolytic streptococci. The MIC values that inhibited 90% of the isolates within each group (MIC90 ) were 0.25 μg/mL for Staphylococcus epidermidis and β-hemolytic streptococci and 0.5 μg/mL for S. aureus , other CoNS, and enterococci. Of 16 isolates with elevated tedizolid or linezolid MIC values (intermediate or resistant isolates), 10 had mutations in the genes encoding 23S rRNA (primarily G2576T), 5 had mutations in the genes encoding ribosomal proteins L3 or L4, and 5 carried the cfr multidrug resistance gene. Overall, tedizolid showed excellent activity against Gram-positive bacteria and was at least 4-fold more potent than linezolid against wild-type and linezolid-resistant isolates. Given the low overall frequency of isolates that would be resistant to tedizolid at the proposed break point of 0.5 μg/mL (0.19%) and potent activity against contemporary US and European isolates, tedizolid has the potential to serve as a valuable therapeutic option in the treatment of infections caused by Gram-positive pathogens.