Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study. Wasserman, S., Brust, J. C M, Abdelwahab, M. T, Little, F., Denti, P., Wiesner, L., Gandhi, N. R, Meintjes, G., & Maartens, G. Journal of Antimicrobial Chemotherapy, 77(4):1146–1154, Oxford University Press (OUP), 2022. ![Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background: Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescri-bers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods: We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifam-picin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results: One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02-0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin .2 g/dL. Trough line-zolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemo-globin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3-6.8). SNPs 2706A. G and 3010G. A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions: Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.
@article{Wasserman2022,
abstract = {Background: Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescri-bers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods: We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifam-picin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results: One hundred and fifty-one participants, 63{\%} HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21{\%}) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14{\%}) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95{\%} CI 0.02-0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin .2 g/dL. Trough line-zolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemo-globin and treatment-emergent anaemia (adjusted OR 2.9; 95{\%} CI 1.3-6.8). SNPs 2706A. G and 3010G. A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions: Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.},
author = {Wasserman, Sean and Brust, James C M and Abdelwahab, Mahmoud T and Little, Francesca and Denti, Paolo and Wiesner, Lubbe and Gandhi, Neel R and Meintjes, Graeme and Maartens, Gary},
doi = {10.1093/JAC/DKAC019},
issn = {0305-7453},
journal = {Journal of Antimicrobial Chemotherapy},
keywords = {OA,anemia,hemoglobin,linezolid,original,toxic effect,trough concentration},
mendeley-tags = {OA,original},
number = {4},
pages = {1146--1154},
pmid = {35134182},
publisher = {Oxford University Press (OUP)},
title = {{Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study}},
url = {https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac019/6520540},
volume = {77},
year = {2022}
}
Downloads: 0
{"_id":"KWfAgPPecfRzSRGuJ","bibbaseid":"wasserman-brust-abdelwahab-little-denti-wiesner-gandhi-meintjes-etal-linezolidtoxicityinpatientswithdrugresistanttuberculosisaprospectivecohortstudy-2022","author_short":["Wasserman, S.","Brust, J. C M","Abdelwahab, M. T","Little, F.","Denti, P.","Wiesner, L.","Gandhi, N. R","Meintjes, G.","Maartens, G."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background: Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescri-bers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods: We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifam-picin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results: One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02-0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin .2 g/dL. Trough line-zolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemo-globin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3-6.8). SNPs 2706A. G and 3010G. A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions: Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.","author":[{"propositions":[],"lastnames":["Wasserman"],"firstnames":["Sean"],"suffixes":[]},{"propositions":[],"lastnames":["Brust"],"firstnames":["James","C","M"],"suffixes":[]},{"propositions":[],"lastnames":["Abdelwahab"],"firstnames":["Mahmoud","T"],"suffixes":[]},{"propositions":[],"lastnames":["Little"],"firstnames":["Francesca"],"suffixes":[]},{"propositions":[],"lastnames":["Denti"],"firstnames":["Paolo"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":[],"lastnames":["Gandhi"],"firstnames":["Neel","R"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]}],"doi":"10.1093/JAC/DKAC019","issn":"0305-7453","journal":"Journal of Antimicrobial Chemotherapy","keywords":"OA,anemia,hemoglobin,linezolid,original,toxic effect,trough concentration","mendeley-tags":"OA,original","number":"4","pages":"1146–1154","pmid":"35134182","publisher":"Oxford University Press (OUP)","title":"Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study","url":"https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac019/6520540","volume":"77","year":"2022","bibtex":"@article{Wasserman2022,\r\nabstract = {Background: Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescri-bers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated. Patients and methods: We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifam-picin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes. Results: One hundred and fifty-one participants, 63{\\%} HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21{\\%}) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14{\\%}) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95{\\%} CI 0.02-0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin .2 g/dL. Trough line-zolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemo-globin and treatment-emergent anaemia (adjusted OR 2.9; 95{\\%} CI 1.3-6.8). SNPs 2706A. G and 3010G. A in mitochondrial DNA were not associated with linezolid toxicity. Conclusions: Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.},\r\nauthor = {Wasserman, Sean and Brust, James C M and Abdelwahab, Mahmoud T and Little, Francesca and Denti, Paolo and Wiesner, Lubbe and Gandhi, Neel R and Meintjes, Graeme and Maartens, Gary},\r\ndoi = {10.1093/JAC/DKAC019},\r\nissn = {0305-7453},\r\njournal = {Journal of Antimicrobial Chemotherapy},\r\nkeywords = {OA,anemia,hemoglobin,linezolid,original,toxic effect,trough concentration},\r\nmendeley-tags = {OA,original},\r\nnumber = {4},\r\npages = {1146--1154},\r\npmid = {35134182},\r\npublisher = {Oxford University Press (OUP)},\r\ntitle = {{Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study}},\r\nurl = {https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac019/6520540},\r\nvolume = {77},\r\nyear = {2022}\r\n}\r\n","author_short":["Wasserman, S.","Brust, J. C M","Abdelwahab, M. T","Little, F.","Denti, P.","Wiesner, L.","Gandhi, N. R","Meintjes, G.","Maartens, G."],"key":"Wasserman2022","id":"Wasserman2022","bibbaseid":"wasserman-brust-abdelwahab-little-denti-wiesner-gandhi-meintjes-etal-linezolidtoxicityinpatientswithdrugresistanttuberculosisaprospectivecohortstudy-2022","role":"author","urls":{"Paper":"https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac019/6520540"},"keyword":["OA","anemia","hemoglobin","linezolid","original","toxic effect","trough concentration"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh","6GMFi5DCojy3jHY44"],"keywords":["oa","anemia","hemoglobin","linezolid","original","toxic effect","trough concentration"],"search_terms":["linezolid","toxicity","patients","drug","resistant","tuberculosis","prospective","cohort","study","wasserman","brust","abdelwahab","little","denti","wiesner","gandhi","meintjes","maartens"],"title":"Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study","year":2022}