Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 60, Issue 4, Pages 2273-2280Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02803-15
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Funding
- Pfizer, Inc.
- Achaogen
- Actavis
- Actelion
- Allergan
- American Proficiency Institute (API)
- AmpliPhi
- Anacor
- Astellas
- AstraZeneca
- Basilea
- Bayer
- BD
- Cardeas
- Cellceutix
- CEM-102 Pharmaceuticals
- Cempra
- Cerexa
- Cidara
- Cormedix
- Cubist
- Debiopharm
- Dipexium
- DongWha
- Durata
- Enteris
- Exela
- Forest Research Institute
- Furiex
- Genentech
- GSK
- Helperby
- ICPD
- Janssen
- Lannett
- Longitude
- Medpace
- Meiji Seika Kasha
- Melinta
- Merck
- Motif
- Nabriva
- Novartis
- Paratek
- Pfizer
- Pocared
- PTC Therapeutics
- Rempex
- Roche
- Salvat
- Scynexis
- Seachaid
- Shionogi
- Tetraphase
- The Medicines Co.
- Theravance
- ThermoFisher
- VenatoRX
- Vertex
- Wockhardt
- Zavante
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The linezolid experience and accurate determination of resistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated were Staphylococcus aureus (3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855), Streptococcus pneumoniae (874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfr and optrA). The MIC50/90 for Staphylococcus aureus was 1/1 mu g/ml, with 47.2% of isolates being methicillin-resistant Staphylococcus aureus. Linezolid was active against all Streptococcus pneumoniae strains and beta-hemolytic streptococci with a MIC50/90 of 1/1 mu g/ml and against viridans group streptococci with a MIC50/90 of 0.5/1 mu g/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harbored cfr only (MIC, 4 mu g/ml), one harbored G2576T (MIC, 8 mu g/ml), and one contained cfr and G2576T with L3 changes (MIC, >= 8 mu g/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of >= 4 mu g/ml. Five of these were identified as Staphylococcus epidermidis, four of which contained cfr in addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (>= 4 mu g/ml; five with G2576T mutations, including one with an additional cfr gene, and one strain with optrA only). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.
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