title: 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.
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.
authors.affiliation: Eurofins Global Central Laboratories, Chantilly, VA, 20151, USA. Electronic address: dsahm@ihmainc.com.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
authors.affiliation: Eurofins Global Central Laboratories, Chantilly, VA, 20151, USA. Electronic address: jdeane@atcc.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deane
authors.affiliation: Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA. Electronic address: pbien74@gmail.com.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bien
authors.affiliation: Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA. Electronic address: jlocke@cidara.com.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Locke
authors.affiliation: Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA. Electronic address: dzuill100@gmail.com.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Zuill
authors.affiliation: Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA. Electronic address: kjshaw3@yahoo.com.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Shaw
authors.affiliation: Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA. Electronic address: kbartizal@cidara.com.
authors.forename: Ken F
authors.initials: KF
authors.lastname: Bartizal
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D062665:Epidemiological Monitoring; D005060:Europe / Q000453:epidemiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010755:Organophosphates / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D012269:Ribosomal Proteins; D000069349:Linezolid; C515040:tedizolid phosphate
keywords: Linezolid; Oxazolidinone; Surveillance; Tedizolid; cfr