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Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)

BACKGROUND: Tedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens ca...

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Autores principales: Mendes, Rodrigo E, Shortridge, Dee, Arends, S J Ryan, Sader, Helio S, Castanheira, Mariana, Flamm, Robert K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631071/
http://dx.doi.org/10.1093/ofid/ofx163.911
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author Mendes, Rodrigo E
Shortridge, Dee
Arends, S J Ryan
Sader, Helio S
Castanheira, Mariana
Flamm, Robert K
author_facet Mendes, Rodrigo E
Shortridge, Dee
Arends, S J Ryan
Sader, Helio S
Castanheira, Mariana
Flamm, Robert K
author_sort Mendes, Rodrigo E
collection PubMed
description BACKGROUND: Tedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens causing community (CA)-acquired and HA infections in the US. METHODS: During the Surveillance of Tedizolid Activity and Resistance (STAR) Program, 10,091 GP isolates were recovered from patients in 31 US hospitals. Isolates were identified by standard biochemical algorithms and MALDI-TOF MS. Susceptibility (S) testing followed CLSI methods and CLSI/EUCAST interpretation. CA and HA infections were defined based on CDC criteria. RESULTS: TZD (MIC(50/90), 0.12/0.12 µg/mL; 100.0%S) showed equivalent MIC(50) and MIC(90) values against MSSA and MRSA, regardless of infection type or origin of isolate (Table). Linezolid (LZD; MIC(50/90), 0.5–1/1 µg/mL; 100.0%S), daptomycin (DAP; MIC(50/90), 0.25/0.5 µg/mL; 99.5–100.0%S), vancomycin (VAN; MIC(50/90), 0.5–1/1 µg/mL; 100.0%S) and trimethoprim-sulfamethoxazole (MIC(50/90), ≤0.5/≤0.5 µg/mL; 93.0–99.5%S) were also active throughout against MSSA and MRSA, while MICs for other agents varied. TZD (MIC(50/90), 0.12/0.25 µg/mL; 100.0%S) activities were consistent against E. faecalis causing various infections from different origins, as were LZD (MIC(50/90), 1/1 µg/mL; 100.0%S), ampicillin (MIC(50/90), 1/1–2 µg/mL; 100.0%S), DAP (MIC(50/90), 1/1–2 µg/mL; 100.0%S), and VAN (MIC(50/90), 1/2 µg/mL; 94.9–97.0%S), although these agents had MIC(50) and MIC(90) values 4- to 8-fold higher than TZD. TZD (MIC(50/90), 0.12/0.25 µg/mL), LZD (MIC(50/90), 1/1–2 µg/mL; 97.6–100.0%S) and DAP (MIC(50/90), 1/2–4 µg/mL; 97.4–100.0%S) were active in vitro against E. faecium, regardless of infection type. S. pneumoniae isolates were S to several drugs tested, and ceftaroline showed the lowest MICs (MIC(50/90), ≤0.015/0.06 µg/mL; 100.0%S). CONCLUSION: TZD had potent in vitro activity against GP isolates causing CA and HA infections in US hospitals, regardless of infection site or bacterial species. The TZD in vitro potency was also generally higher than clinically available comparator agents. DISCLOSURES: R. E. Mendes, Merck: Research Contractor, Research grant; 
D. Shortridge, Merck: Research Contractor, Research grant; S. J. R. Arends, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; M. Castanheira, Merck: Research Contractor, Research grant; 
R. K. Flamm, Merck: Research Contractor, Research grant
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spelling pubmed-56310712017-11-07 Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016) Mendes, Rodrigo E Shortridge, Dee Arends, S J Ryan Sader, Helio S Castanheira, Mariana Flamm, Robert K Open Forum Infect Dis Abstracts BACKGROUND: Tedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens causing community (CA)-acquired and HA infections in the US. METHODS: During the Surveillance of Tedizolid Activity and Resistance (STAR) Program, 10,091 GP isolates were recovered from patients in 31 US hospitals. Isolates were identified by standard biochemical algorithms and MALDI-TOF MS. Susceptibility (S) testing followed CLSI methods and CLSI/EUCAST interpretation. CA and HA infections were defined based on CDC criteria. RESULTS: TZD (MIC(50/90), 0.12/0.12 µg/mL; 100.0%S) showed equivalent MIC(50) and MIC(90) values against MSSA and MRSA, regardless of infection type or origin of isolate (Table). Linezolid (LZD; MIC(50/90), 0.5–1/1 µg/mL; 100.0%S), daptomycin (DAP; MIC(50/90), 0.25/0.5 µg/mL; 99.5–100.0%S), vancomycin (VAN; MIC(50/90), 0.5–1/1 µg/mL; 100.0%S) and trimethoprim-sulfamethoxazole (MIC(50/90), ≤0.5/≤0.5 µg/mL; 93.0–99.5%S) were also active throughout against MSSA and MRSA, while MICs for other agents varied. TZD (MIC(50/90), 0.12/0.25 µg/mL; 100.0%S) activities were consistent against E. faecalis causing various infections from different origins, as were LZD (MIC(50/90), 1/1 µg/mL; 100.0%S), ampicillin (MIC(50/90), 1/1–2 µg/mL; 100.0%S), DAP (MIC(50/90), 1/1–2 µg/mL; 100.0%S), and VAN (MIC(50/90), 1/2 µg/mL; 94.9–97.0%S), although these agents had MIC(50) and MIC(90) values 4- to 8-fold higher than TZD. TZD (MIC(50/90), 0.12/0.25 µg/mL), LZD (MIC(50/90), 1/1–2 µg/mL; 97.6–100.0%S) and DAP (MIC(50/90), 1/2–4 µg/mL; 97.4–100.0%S) were active in vitro against E. faecium, regardless of infection type. S. pneumoniae isolates were S to several drugs tested, and ceftaroline showed the lowest MICs (MIC(50/90), ≤0.015/0.06 µg/mL; 100.0%S). CONCLUSION: TZD had potent in vitro activity against GP isolates causing CA and HA infections in US hospitals, regardless of infection site or bacterial species. The TZD in vitro potency was also generally higher than clinically available comparator agents. DISCLOSURES: R. E. Mendes, Merck: Research Contractor, Research grant; 
D. Shortridge, Merck: Research Contractor, Research grant; S. J. R. Arends, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; M. Castanheira, Merck: Research Contractor, Research grant; 
R. K. Flamm, Merck: Research Contractor, Research grant Oxford University Press 2017-10-04 /pmc/articles/PMC5631071/ http://dx.doi.org/10.1093/ofid/ofx163.911 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Mendes, Rodrigo E
Shortridge, Dee
Arends, S J Ryan
Sader, Helio S
Castanheira, Mariana
Flamm, Robert K
Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title_full Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title_fullStr Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title_full_unstemmed Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title_short Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
title_sort activity of tedizolid against gram-positive clinical isolates causing nosocomial- and community-acquired infections in united states hospitals (2014–2016)
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631071/
http://dx.doi.org/10.1093/ofid/ofx163.911
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