Assessment of Linezolid Efficacy, Safety and Tolerability in the Treatment of Tuberculosis: A Retrospective Case Review

Tse-Chang, Alena; Kunimoto, Dennis; Der, Evelina; Ahmed, Rabia

doi:10.1155/2013/535616

Cited by 11 publications

(7 citation statements)

References 16 publications

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“…These results support further clinical evaluation of AZD5847 since the efficacy of LZD in TB patients appears good (27–30). Since the primary concerns with wider usage of LZD revolve around safety issues, this newer oxazolidinone may well show less side effects.…”

Section: Discussionsupporting

confidence: 78%

PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis

et al. 2014

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Oxazolidinone antibiotics such as linezolid have shown significant therapeutic effects in patients with extensively drug-resistant (XDR) tuberculosis (TB) despite modest effects in rodents and no demonstrable early bactericidal activity in human phase 2 trials. We show that monotherapy with either linezolid or AZD5847, a second-generation oxazolidinone, reduced bacterial load at necropsy in Mycobacterium tuberculosis-infected cynomolgus macaques with active TB. This effect coincided with a decline in 2-deoxy-2-[(18)F]-fluoro-d-glucose positron emission tomography (FDG PET) imaging avidity in the lungs of these animals and with reductions in pulmonary pathology measured by serial computed tomography (CT) scans over 2 months of monotherapy. In a parallel phase 2 clinical study of linezolid in patients infected with XDR-TB, we also collected PET/CT imaging data from subjects receiving linezolid that had been added to their failing treatment regimens. Quantitative comparisons of PET/CT imaging changes in these human subjects were similar in magnitude to those observed in macaques, demonstrating that the therapeutic effect of these oxazolidinones can be reproduced in this model of experimental chemotherapy. PET/CT imaging may be useful as an early quantitative measure of drug efficacy against TB in human patients.

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Section: Discussionsupporting

confidence: 78%

PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis

et al. 2014

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“… Tang et al [ 51 ] 2015 China Prospective multicenter randomized controlled study Yes 33 2009–2011 65 1200 mg daily 300–600 mg daily Range = 2–24 months Individualized All HIV negative 18. Tse-Chang et al [ 52 ] 2013 Canada Retrospective case study No 13 2000–2011 NR 600 mg daily Mean = 8.3 months Range = 1.4–22 months Individualized 1 HIV positive 19. Udwadia et al [ 53 ] 2010 India Prospective non-randomized case series No 18 2000–2007 7 600 mg daily Mean = 21 months Individualized NR 20.…”

Section: Resultsmentioning

confidence: 99%

“… Tang et al [ 51 ] Yes Yes Yes NR Yes Yes 18. Tse-Chang et al [ 52 ] NR Yes Yes NR NR Yes 19. Udwadia et al [ 53 ] Yes Yes Yes No NR NR 20.…”

Section: Resultsmentioning

confidence: 99%

“…Only two studies [ 38 , 46 ] had less than 50 % treatment success with linezolid dose regimen between 600 and 1200 mg daily. Three studies [ 35 , 37 , 52 ] reported 100 % treatment success (95 % CI = 78.20–100, 54.07–100 and 66.37–100 %, respectively).

Fig.…”

Section: Resultsmentioning

confidence: 99%

“…5 ) and high heterogeneity of 83 %. The Canadian cohort [ 52 ] recorded the highest incidence of myelosuppression of 85 % (11 out 13 patients) at a linezolid dose of 600 mg daily. Koh et al [ 40 ] recorded the least occurrence of myelosuppression; 4 % (1 out of 24 patients) with daily 300 mg dose of linezolid.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis

Agyeman

Ofori‐Asenso

2016

Ann Clin Microbiol Antimicrob

109

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BackgroundTreatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.ObjectiveTo systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.MethodsWe conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.ResultsTwenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38–82.83 %, I2 = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82–92.38 %, I2 = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).ConclusionAvailable evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12941-016-0156-y) contains supplementary material, which is available to authorized users.

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Linezolid for drug-resistant pulmonary tuberculosis

Singh

Cocker

Ryan

et al. 2019

Cochrane Database of Systematic Reviews

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BackgroundLinezolid was recently re‐classified as a Group A drug by the World Health Organization (WHO) for treatment of multi‐drug resistant tuberculosis (MDR‐TB) and extensively drug‐resistant tuberculosis (XDR‐TB), suggesting that it should be included in the regimen for all patients unless contraindicated. Linezolid use carries a considerable risk of toxicity, with the optimal dose and duration remaining unclear. Current guidelines are mainly based on evidence from observational non‐comparative studies.ObjectivesTo assess the efficacy of linezolid when used as part of a second‐line regimen for treating people with MDR and XDR pulmonary tuberculosis, and to assess the prevalence and severity of adverse events associated with linezolid use in this patient group.Search methodsWe searched the following databases: the Cochrane Infectious Diseases Specialized Register; CENTRAL; MEDLINE; Embase; and LILACS up to 13 July 2018. We also checked article reference lists and contacted researchers in the field.Selection criteriaWe included studies in which some participants received linezolid, and others did not. We included randomized controlled trials (RCTs) of linezolid for MDR and XDR pulmonary tuberculosis to evaluate efficacy outcomes. We added non‐randomized cohort studies to evaluate adverse events.Primary outcomes were all‐cause and tuberculosis‐associated death, treatment failure, and cure. Secondary outcomes were treatment interrupted, treatment completed, and time to sputum culture conversion. We recorded frequency of all and serious adverse events, adverse events leading to drug discontinuation or dose reduction, and adverse events attributed to linezolid, particularly neuropathy, anaemia, and thrombocytopenia.Data collection and analysisTwo review authors (BS and DC) independently assessed the search results for eligibility and extracted data from included studies. All review authors assessed risk of bias using the Cochrane ‘Risk of bias' tool for RCTs and the ROBINS‐I tool for non‐randomized studies. We contacted study authors for clarification and additional data when necessary.We were unable to perform a meta‐analysis as one of the RCTs adopted a study design where participants in the study group received linezolid immediately and participants in the control group received linezolid after two months, and therefore there were no comparable data from this trial. We deemed meta‐analysis of non‐randomized study data inappropriate.Main resultsWe identified three RCTs for inclusion. One of these studies had serious problems with allocation of the study drug and placebo, so we could not analyse data for intervention effect from it. The remaining two RCTs recruited 104 participants. One randomized 65 participants to receive linezolid or not, in addition to a background regimen; the other randomized 39 participants to addition of linezolid to a background regimen immediately, or after a delay of two months. We included 14 non‐randomized cohort studies (two prospective, 12 retrospective), with a total of 1678 partici...

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Assessment of Linezolid Efficacy, Safety and Tolerability in the Treatment of Tuberculosis: A Retrospective Case Review

Cited by 11 publications

References 16 publications

PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis

PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis

Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis

Linezolid for drug-resistant pulmonary tuberculosis

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