333 - Tedizolid Activity against Gram-Positive Bacterial Isolates Causing Bone and Joint Infections in the United States (2015-2019)

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Presenting Author(s)

Cecilia G. Carvalhaes

Associate Director for Clinical Microbiology
JMI Laboratories
North Liberty, IA
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)

Co-Author(s)

Helio S. Sader

Senior Director, Microbiology & Surveillance
JMI Laboratories
North Liberty, IA
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)
JS

Jennifer M. Streit

Surveillance Manager
JMI Laboratories
North Liberty, Iowa
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)
Mariana Castanheira

Chief Scientific Officer
JMI Laboratories
North Liberty, Iowa
Disclosure: 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)
RM

Rodrigo E. Mendes

Director of Microbiology & Molecular Biology
JMI Laboratories
North Liberty, Iowa
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Background: Prolonged systemic antibiotic courses are frequently used to manage difficult-to-treat bone and joint infections (BJI). Tedizolid has been considered as a therapy candidate for BJI in adults and children. This study assessed the in vitro activity of tedizolid and comparator agents against a contemporary collection of Gram-positive (GP) isolates causing BJI in the US.

Methods: A total of 310 Staphylococcus aureus (SA), 79 β-hemolytic streptococci (BHS), 52 coagulase-negative staphylococci (CoNS), and 37 Enterococcus faecalis isolates were included in this study. These isolates were collected from patients with BJI from 30 medical centers in the US between 2015 and 2019 as a part of the Surveillance of Tedizolid Activity and Resistance (STAR) Program. Bacterial identification was confirmed by MALDI-TOF MS. MIC results were obtained by reference CLSI broth microdilution methods and interpretations used CLSI guidelines.

Results: Tedizolid (MIC_50/90, 0.12/0.25 mg/L) inhibited all SA at the CLSI breakpoint (≤0.5 mg/L) including methicillin-resistant SA (MRSA; 35.8% of SA; MIC_50/90, 0.12/0.25 mg/L). Linezolid, vancomycin, and daptomycin had 100% susceptibility rates against SA isolates (Table). All CoNS isolates were inhibited by tedizolid at ≤0.5 mg/L. Tedizolid was active against all BHS (100% susceptible) as follows: S. pyogenes (n=24; MIC_50/90, 0.12/0.25 mg/L), S. agalactiae (n=44; MIC_50/90, 0.12/0.25 mg/L), and S. dysgalactiae (n= 11; MIC_50/90, 0.25/0.25 mg/L). Penicillin, linezolid, vancomycin, and daptomycin also were active against BHS (100% susceptible). Tedizolid (MIC_50/90, 0.25/0.25 mg/L; 100% susceptible) was 4- to 8-fold more potent than linezolid (MIC_50/90, 1/1 mg/L) and vancomycin (MIC_50/90, 1/2 mg/L) against E. faecalis. GP isolates resistant to oxazolidinone were not observed.

Conclusion: Tedizolid demonstrated potent in vitro activity against this collection of contemporary GP isolates causing BJI in US hospitals. Tedizolid and comparator agents showed high susceptibility rates against the most frequent organisms and organism groups, including MRSA. These findings support the clinical development of tedizolid as an additional option for treating BJI caused by GP pathogens.Table 1