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Safety and tolerability of tedizolid as oral treatment for bone and joint infections

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxa...

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Autores principales: Miller, Loren G., Flores, Evelyn A., Launer, Bryn, Lee, Pamela, Kalkat, Praneet, Derrah, Kelli, Agrawal, Shalini, Schwartz, Matthew, Steele, Grant, Kim, Tae, Kuvhenguhwa, Maita S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581034/
https://www.ncbi.nlm.nih.gov/pubmed/37750695
http://dx.doi.org/10.1128/spectrum.01282-23
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author Miller, Loren G.
Flores, Evelyn A.
Launer, Bryn
Lee, Pamela
Kalkat, Praneet
Derrah, Kelli
Agrawal, Shalini
Schwartz, Matthew
Steele, Grant
Kim, Tae
Kuvhenguhwa, Maita S.
author_facet Miller, Loren G.
Flores, Evelyn A.
Launer, Bryn
Lee, Pamela
Kalkat, Praneet
Derrah, Kelli
Agrawal, Shalini
Schwartz, Matthew
Steele, Grant
Kim, Tae
Kuvhenguhwa, Maita S.
author_sort Miller, Loren G.
collection PubMed
description Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4–12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4–12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE: Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.
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spelling pubmed-105810342023-10-18 Safety and tolerability of tedizolid as oral treatment for bone and joint infections Miller, Loren G. Flores, Evelyn A. Launer, Bryn Lee, Pamela Kalkat, Praneet Derrah, Kelli Agrawal, Shalini Schwartz, Matthew Steele, Grant Kim, Tae Kuvhenguhwa, Maita S. Microbiol Spectr Research Article Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4–12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4–12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE: Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections. American Society for Microbiology 2023-09-26 /pmc/articles/PMC10581034/ /pubmed/37750695 http://dx.doi.org/10.1128/spectrum.01282-23 Text en Copyright © 2023 Miller et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Miller, Loren G.
Flores, Evelyn A.
Launer, Bryn
Lee, Pamela
Kalkat, Praneet
Derrah, Kelli
Agrawal, Shalini
Schwartz, Matthew
Steele, Grant
Kim, Tae
Kuvhenguhwa, Maita S.
Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title_full Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title_fullStr Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title_full_unstemmed Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title_short Safety and tolerability of tedizolid as oral treatment for bone and joint infections
title_sort safety and tolerability of tedizolid as oral treatment for bone and joint infections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581034/
https://www.ncbi.nlm.nih.gov/pubmed/37750695
http://dx.doi.org/10.1128/spectrum.01282-23
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