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1. Linezolid for the Treatment of Infections: A Review of the Clinical and Cost-Effectiveness

Linezolid for the Treatment of Infections: A Review of the Clinical and Cost-Effectiveness Linezolid for the Treatment of Infections: A Review of the Clinical and Cost-Effectiveness | CADTH.ca Find the information you need Linezolid for the Treatment of Infections: A Review of the Clinical and Cost-Effectiveness Linezolid for the Treatment of Infections: A Review of the Clinical and Cost-Effectiveness Published on: October 25, 2017 Project Number: RD0041-000 Product Line: Research Type: Drug (...) Report Type: Peer-reviewed summary with critical appraisal Result type: Report Question What is the comparative clinical effectiveness of linezolid to vancomycin or daptomycin in the treatment of bacteremia, bone and joint infections, skin and soft tissue infections, and pneumonia caused by methicillin-resistant staphylococcus aureus (MRSA)? What is the comparative clinical effectiveness of linezolid to daptomycin in the treatment of bacteremia, bone and joint infection, infective endocarditis, intra

2017 Canadian Agency for Drugs and Technologies in Health - Rapid Review

2. Linezolid versus vancomycin for skin and soft tissue infections. (PubMed)

Linezolid versus vancomycin for skin and soft tissue infections. The morbidity and treatment costs associated with skin and soft tissue infections (SSTIs) are high. Linezolid and vancomycin are antibiotics that are commonly used in treating skin and soft-tissue infections, specifically those infections due to methicillin-resistant Staphylococcus aureus (MRSA).To compare the effects and safety of linezolid and vancomycin for treating people with SSTIs.For this first update of this review we (...) randomised controlled trials (RCTs) comparing linezolid with vancomycin in the treatment of SSTIs.Two review authors independently selected trials, assessed risk of bias and extracted data. The primary outcomes were clinical cure, microbiological cure, and SSTI-related and treatment-related mortality. We performed subgroup analyses according to age, and whether the infection was due to MRSA.No new trials were identified for this first update. We included nine RCTs (3144 participants). Linezolid

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2016 Cochrane

3. Dissemination of linezolid-dependent, linezolid-resistant Staphylococcus epidermidis clinical isolates belonging to CC5 in German hospitals. (PubMed)

Dissemination of linezolid-dependent, linezolid-resistant Staphylococcus epidermidis clinical isolates belonging to CC5 in German hospitals. Linezolid-resistant Staphylococcus epidermidis (LRSE) and linezolid-dependent ST22 strains have been shown to predominate in tertiary care facilities all over Greece. We report herein the dissemination of ST22 but also ST2, ST5 and ST168 linezolid-dependent LRSE clones in four unrelated German hospitals.Fourteen LRSE clinical isolates recovered during 2012 (...) -14 from five distantly located German hospitals were tested by for MIC determination broth microdilution and Etest, PCR/sequencing for cfr and for mutations in 23S rRNA, rplC, rplD and rplV genes, MLST, PFGE and growth curves without and with linezolid at 16 and 32 mg/L.Most (11, 78.6%) isolates had linezolid MICs >256 mg/L. Five isolates carried the cfr gene. Eight isolates belonged to ST22, two isolates each to ST168 and ST2 and one isolate each to ST5 and ST23. Ten isolates [seven belonging

2018 Journal of Antimicrobial Chemotherapy

4. Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With Linezolid-Resistant Staphylococcus epidermidis Bacteremia (PubMed)

Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With Linezolid-Resistant Staphylococcus epidermidis Bacteremia Coagulase-negative staphylococci, including Staphylococcus epidermidis, are the most common cause of bloodstream infection in cancer patients. Linezolid resistance is increasingly identified in S. epidermidis, but whether such resistance alters the clinical course of S. epidermidis infections is unknown. The purpose of this study was to assess the clinical (...) impact of linezolid resistance in leukemia patients with S. epidermidis bloodstream infection.This was a retrospective, single-center cohort study of all adult leukemia patients with S. epidermidis bacteremia treated with empiric linezolid between 2012 and 2015. The primary end point was adverse clinical outcome on day 3, defined as a composite of persistent bacteremia, fever, intensive care unit admission, or death. Fourteen- and 30-day mortality were also assessed.Eighty-two unique leukemia

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2018 Open forum infectious diseases

5. Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy. (PubMed)

Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy. Linezolid is a monoamine oxidase inhibitor that may increase the risk of serotonin syndrome in patients receiving combination selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). The objective of this study was to compare the incidence of serotonin syndrome when linezolid was administered alone (...) and in combination with SSRIs or SNRIs.This was a retrospective case-control study of adult inpatients admitted to the University of Iowa Hospitals and Clinics who received linezolid between January 2010 and December 2014. Patients who received linezolid with or within 14 days of an SSRI or SNRI were eligible for inclusion in the combination therapy group. Patients who received linezolid alone were matched by age and gender to patients in the combination therapy group, and 3 monotherapy patients were included

2017 Journal of Clinical Psychopharmacology

6. Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance (PubMed)

Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance The significant increase of the linezolid-resistant enterococci (LRE) has been observed in Polish hospitals since 2012 and our study aimed at elucidating the possible reasons for this phenomenon. Polish LRE isolates were analysed by multilocus-sequence typing (MLST) and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA), polymerase chain reaction (PCR) and PCR (...) -restriction fragment length polymorphism (PCR-RFLP) to establish clonal relatedness and mechanism of linezolid resistance, respectively. Fifty analysed LRE (2008-2015) included mostly Enterococcus faecium (82%) and Enterococcus faecalis (16%). Enterococcus faecium belonged to the hospital-adapted lineages 17/18 and 78, while E. faecalis isolates represented ST6, a hospital-associated type, and ST116, found in both humans and food-production animals. The G2576T 23S rRNA mutation was the most frequent (94

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2017 European Journal of Clinical Microbiology & Infectious Diseases

7. In vitro activity of daptomycin combined with dalbavancin and linezolid, and dalbavancin with linezolid against MRSA strains. (PubMed)

In vitro activity of daptomycin combined with dalbavancin and linezolid, and dalbavancin with linezolid against MRSA strains. Combination therapies have a distinct advantage over monotherapies in terms of their broad spectrum, synergistic effect and prevention of the emergence of drug resistance. In the present study, the in vitro antibacterial activity of daptomycin combinations with linezolid and dalbavancin, and dalbavancin with linezolid were evaluated against 30 clinical MRSA strains.The (...) MICs of all antibiotics were determined using microbroth dilution as described by the CLSI. The in vitro activities of antibiotics in combination were assessed by using a microbroth 'chequerboard' assay. The MIC values of all antibiotics determined were evaluated in accordance with the recommendations of the CLSI for daptomycin and linezolid, and the FDA for dalbavancin.All strains (100%) were found to be susceptible to daptomycin, dalbavancin and linezolid. The MIC50, MIC90 and MICrange values

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2016 Journal of Antimicrobial Chemotherapy

8. Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis: Effectiveness of linezolid in the elderly. (PubMed)

Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis: Effectiveness of linezolid in the elderly. Several reports have compared the efficacy of linezolid (LZD) in Methicillin-resistant Staphylococcus aureus (MRSA) infections with that of vancomycin (VCM); however, these two antibiotics for the treatment of nosocomial MRSA pneumonia in elderly patients has not been well evaluated. The purpose

2016 American Journal of Emergency Medicine

9. Population pharmacokinetics and dosing optimization of linezolid in pediatric patients. (PubMed)

Population pharmacokinetics and dosing optimization of linezolid in pediatric patients. Background: Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize dosing (...) be required for them.Conclusion: The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.Copyright © 2019 American Society for Microbiology.

2019 Antimicrobial Agents and Chemotherapy

10. Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of HIV co-infection. (PubMed)

Linezolid pharmacokinetics in South African patients with drug resistant tuberculosis and a high prevalence of HIV co-infection. The World Health Organization (WHO) recently recommended that linezolid be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in patients with this disease. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic (...) target attainment in South African patients with drug-resistant TB. Consecutive adults on linezolid-based regimens were recruited in Cape Town and underwent intensive PK sampling at steady state. Noncompartmental analysis was performed. Thirty participants were included: 15 HIV positive, 26 on the initial dose of 600 mg daily, and 4 participants on 300 mg daily after dose reduction for linezolid-related toxicity. There was a negative correlation between body weight and exposure, with 17.4% (95

2019 Antimicrobial Agents and Chemotherapy

11. Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, m (PubMed)

Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, m Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) remain unsatisfactory, and long-term use of second-line anti-TB drugs is accompanied by the frequent occurrence of adverse events, low treatment compliance, and high costs (...) uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence

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2019 Trials

12. LRE-Finder, a Web tool for detection of the 23S rRNA mutations and the optrA, cfr, cfr(B) and poxtA genes encoding linezolid resistance in enterococci from whole-genome sequences. (PubMed)

LRE-Finder, a Web tool for detection of the 23S rRNA mutations and the optrA, cfr, cfr(B) and poxtA genes encoding linezolid resistance in enterococci from whole-genome sequences. In enterococci, resistance to linezolid is often mediated by mutations in the V domain of the 23S rRNA gene (G2576T or G2505A). Furthermore, four genes [optrA, cfr, cfr(B) and poxtA] encode linezolid resistance in enterococci. We aimed to develop a Web tool for detection of the two mutations and the four genes (...) encoding linezolid resistance in enterococci from whole-genome sequence data.LRE-Finder (where LRE stands for linezolid-resistant enterococci) detected the fraction of Ts in position 2576 and the fraction of As in position 2505 of the 23S rRNA and the cfr, cfr(B), optrA and poxtA genes by aligning raw sequencing reads (fastq format) with k-mer alignment. For evaluation, fastq files from 21 LRE isolates were submitted to LRE-Finder. As negative controls, fastq files from 1473 non-LRE isolates were

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2019 Journal of Antimicrobial Chemotherapy

13. Contribution of pretomanid to novel regimens containing bedaquiline with either linezolid or moxifloxacin and pyrazinamide in murine models of tuberculosis. (PubMed)

Contribution of pretomanid to novel regimens containing bedaquiline with either linezolid or moxifloxacin and pyrazinamide in murine models of tuberculosis. Novel regimens combining bedaquiline and pretomanid with either linezolid (BPaL regimen) or moxifloxacin and pyrazinamide (BPaMZ regimen) shorten the treatment duration needed to cure TB in BALB/c mice compared to the first-line regimen and have yielded promising results in initial clinical trials. However, the independent contribution

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2019 Antimicrobial Agents and Chemotherapy

14. Efficacy and safety of tedizolid phosphate versus linezolid in a randomized Phase 3 trial in patients with acute bacterial skin and skin structure infection. (PubMed)

Efficacy and safety of tedizolid phosphate versus linezolid in a randomized Phase 3 trial in patients with acute bacterial skin and skin structure infection. Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the USA, Europe, and other countries.In this multicenter, double-blind, Phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the USA were randomized to receive (...) tedizolid 200 mg, intravenous (IV)/oral (PO), once daily for 6 days or linezolid 600 mg, IV/PO twice daily for 10 days. The primary endpoint was early clinical response rate at 48-72 hours. Secondary endpoints included programmatic and investigator-assessed outcomes at end-of-therapy (EOT) and post-therapy evaluation (PTE) visits. Safety was also evaluated.In the intent-to-treat (ITT) population, 75.3% of tedizolid-treated patients and 79.9% of linezolid-treated patients were early responders (treatment

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2019 Antimicrobial Agents and Chemotherapy

15. Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: Combined data from two prospective observational studies. (PubMed)

Pharmacokinetics, optimal dosing, and safety of linezolid in children with multidrug-resistant tuberculosis: Combined data from two prospective observational studies. Linezolid is increasingly important for multidrug-resistant tuberculosis (MDR-TB) treatment. However, among children with MDR-TB, there are no linezolid pharmacokinetic data, and its adverse effects have not yet been prospectively described. We characterised the pharmacokinetics, safety, and optimal dose of linezolid in children (...) treated for MDR-TB.Children routinely treated for MDR-TB in 2 observational studies (2011-2015, 2016-2018) conducted at a single site in Cape Town, South Africa, underwent intensive pharmacokinetic sampling after either a single dose or multiple doses of linezolid (at steady state). Linezolid pharmacokinetic parameters, and their relationships with covariates of interest, were described using nonlinear mixed-effects modelling. Children receiving long-term linezolid as a component of their routine

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2019 PLoS medicine

16. Characterization of linezolid-resistance-associated mutations in Mycobacterium tuberculosis through WGS. (PubMed)

Characterization of linezolid-resistance-associated mutations in Mycobacterium tuberculosis through WGS. Linezolid is becoming an important antibiotic for treating MDR/XDR TB, but the mutations conferring resistance to linezolid remain inadequately characterized. Herein, we investigated the linezolid-resistance-associated mutations on a whole-genome scale through parallel selections of resistant isolates in vitro.Ten parallel Mycobacterium tuberculosis H37Rv cultures were subjected (...) to spontaneous mutant selection on 7H11 agar plates containing 2.5 mg/L linezolid. The linezolid resistance of resulting colonies was confirmed by growth on a second linezolid plate. WGS was then performed to identify mutations associated with linezolid resistance.Of 181 colonies appearing on the initial linezolid plates, 154 were confirmed to be linezolid resistant. WGS showed that 88.3% (136/154) of these isolates had a T460C mutation in rplC, resulting in a C154R substitution. The other 18 isolates

2019 Journal of Antimicrobial Chemotherapy

17. Dispersal of linezolid-resistant enterococci carrying poxtA or optrA in retail meat and food-producing animals from Tunisia. (PubMed)

Dispersal of linezolid-resistant enterococci carrying poxtA or optrA in retail meat and food-producing animals from Tunisia. The epidemiology of Enterococcus resistant to priority antibiotics including linezolid has mainly been investigated in developed countries and especially in hospitals. We aimed to evaluate the contribution of different non-human reservoirs for the burden of MDR enterococci in Tunisia, where scarce data are available.Samples (n = 287) were collected from urban wastewater (...) ; EUCAST/CLSI) and clonality (SmaI-PFGE/MLST).All samples carried Enterococcus (n = 377 isolates) resistant to antibiotics considered to be critical or highly important by WHO. Even without antibiotic selection, 38% of Enterococcus faecalis (Efs) and 22% of Enterococcus faecium (Efm) were identified as MDR. Linezolid-resistant isolates (5%; MIC = 8 mg/L) comprised six poxtA-carrying Efm (cow milk), seven optrA-carrying Efs (chicken faeces/meat) and five Efm lacking cfr/optrA/poxtA (poultry/bovine/ovine

2019 Journal of Antimicrobial Chemotherapy

18. Linezolid versus vancomycin for skin and soft tissue infections. (PubMed)

Linezolid versus vancomycin for skin and soft tissue infections. The morbidity and treatment costs associated with skin and soft tissue infections (SSTIs) are high. Linezolid and vancomycin are antibiotics that are commonly used in treating skin and soft-tissue infections, specifically those infections due to methicillin-resistant Staphylococcus aureus (MRSA).To compare the effects and safety of linezolid and vancomycin for treating people with SSTIs.In May 2013 we conducted searches (...) linezolid with vancomycin in the treatment of SSTIs.Two review authors independently selected trials, assessed risk of bias and extracted data. The primary outcomes were clinical cure, microbiological cure, and SSTI-related and treatment-related mortality. We performed subgroup analyses according to age, and whether the infection was due to MRSA.We included nine RCTs (3144 participants). Linezolid was associated with a significantly better clinical (RR 1.09, 95% CI 1.03 to 1.16) and microbiological cure

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2013 Cochrane

19. Intrathecal/Intraventricular Linezolid in Multidrug-Resistant Enterococcus faecalis Ventriculitis (PubMed)

Intrathecal/Intraventricular Linezolid in Multidrug-Resistant Enterococcus faecalis Ventriculitis Background The use of intrathecal antibiotic therapy for the treatment of ventriculitis and/or meningitis has demonstrated efficacy especially when sterilization of the cerebrospinal fluid is not possible with intravenous antibiotics alone. Case Description We describe the successful treatment of Enterococcus faecalis ventriculitis utilizing intrathecal linezolid in a 32-year-old female patient (...) with severe allergy to vancomycin, prohibitive bacterial susceptibilities, and failure of previous attempts to sterilize the cerebrospinal fluid despite multimodal treatment. Conclusion Intrathecal linezolid is a useful treatment in the setting of multidrug-resistant bacterial ventriculitis. We present a useful dosing regimen for the administration of intrathecal linezolid.

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2016 Journal of neurological surgery reports

20. Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan - Results of a randomised, multicentre phase 3 study. (PubMed)

Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan - Results of a randomised, multicentre phase 3 study. The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs (...) population up to follow up. Data analysis was descriptive in nature. Baseline characteristics of patients were similar between treatment groups. At TOC in the ME-MRSA population, clinical cure rate was similar in tedizolid phosphate (92.6%) and linezolid (88.9%) groups. At EOT, clinical cure (tedizolid phosphate: 93.1%, linezolid: 90.0%) and microbiological success (tedizolid phosphate: 93.1%, linezolid: 100.0%) rates were similar in the ME-MRSA population. Both treatments were well tolerated; overall

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2018 Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy

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