Summary - Linezolid Plasma Dosing MAY 2024 Linezolid Plasma Dosing English summary Une production de l’Institut national d’excellence en santé et en services sociaux (INESSS) 1 SUMMARY Linezolid Plasma Dosing Introduction The Institut national d'excellence en santé et en services sociaux (INESSS) has received a request to include a new assay in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the "Répertoire"), through the mechanism for evaluating new medical biology assays. The mandate is to assess the relevance of including linezolid in the Repertoire as part of Therapeutic Drug Monitoring (TDM). This is the second evaluation for this mandate. As this request includes new elements, the INESSS has re-evaluated the relevance
What are the hepatic effects of linezolid? Chiefs’ Inquiry Corner – 2/14/22 – Clinical Correlations Clinical Correlations * AboutAboutAwardsPeer Review * CategoriesBedside RoundsChiefs' Inquiry CornerCORE IM PodcastDiseases 2.0EthicsEvolution and MedicineGamechanger?Healthcare PolicyHotSpotsMystery QuizMyths and RealitiesPrimeCutsSpotlightSee All Categories * SystemsAllergy , both in their clinics and on the wards.Click to toggle the answers!Bellevue Inpatient:What are the hepatic effects of linezolid? Linezolid is a synthetic antibiotic that belongs to the oxazolidinone class and has broad bactericidal activity against gram positive organisms (e.g., enterococci and staphylococci, as well as most streptococci) in addition to moderate activity against Mycobacterium
LInezolid Monitoring to MInimise Toxicity (LIMMIT1): a multicentre retrospective review of patients receiving linezolid therapy and the impact of therapeutic drug monitoring. Linezolid is a broad-spectrum antimicrobial but toxicity limits it use. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity , including the impact of therapeutic drug monitoring (TDM). Patients administered linezolid between January 2017 and December 2019 were reviewed retrospectively. Data was collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between patients who did and did not experience linezolid toxicity
Establishment and validation of a risk prediction model incorporating concentrations of linezolid and its metabolite PNU142300 for linezolid-induced thrombocytopenia. Linezolid-induced thrombocytopenia is the main factor restricting the clinical application of linezolid. To investigate the relationship between PNU-14230 concentration and linezolid-induced thrombocytopenia and further develop and validate a risk model for predicting linezolid-induced thrombocytopenia. A regression model was constructed to predict the occurrence of linezolid-induced thrombocytopenia, and further externally validated. The predictive performance was evaluated by receiver operating characteristic curve and Hosmer-Lemeshow test. Linezolid Cmin and PNU-142300 concentrations were compared for different kidney function
A new perspective on the antimicrobial mechanism of linezolid against Staphylococcus aureus revealed by proteomics and metabolomics analysis. Understanding bacterial responses to antimicrobials is crucial for identifying tolerance mechanisms and developing new therapies. Using mass spectrometry-based metabolomics and proteomics, this study examines the response of Staphylococcus aureus to linezolid (LZD) treatment. Under LZD stress, significant fluctuations were observed in key metabolic pathways such as amino acid biosynthesis and the TCA cycle, alongside a general increase in ribosomal protein complexes. Additionally, LZD disrupted nucleotide metabolism, particularly affecting pyrimidine pathways. Combining LZD with the pyrimidine synthesis inhibitor leflunomide enhanced bactericidal
Linezolid Dosing and Pharmacokinetics in North American Patients with Tuberculosis. Linezolid is recommended in treatment regimens for rifampin- or multi-drug-resistant tuberculosis. However, considerable pharmacokinetic variability exists, and long-term use is limited by adverse effects. This study evaluates the pharmacokinetics of linezolid in patients with tuberculosis from an international therapeutic drug monitoring service. Linezolid trough, 2-hour, and 6-hour post-dose clinical samples from across North America were tested by the University of Florida Infectious Disease Pharmacokinetics Laboratory. Total serum concentrations were measured using liquid chromatography-tandem mass spectrometry. Therapeutic drug monitoring was performed, and measurements were compared to typical linezolid
Vancomycin versus linezolid for treatment of staphylococcal-associated central nervous system infections. Linezolid and vancomycin are both recommended for the treatment of staphylococcal-associated central nervous system (CNS) infections. However, to date, no data are available comparing the outcomes of patients treated with vancomycin or linezolid for these infections. The aim of this study was to compare the incidence of treatment failure and adverse events (AEs) associated with vancomycin and linezolid in staphylococcal-associated CNS infections. This retrospective monocentric observational study was conducted between 01/01/2015 and 31/12/2023. All patients with a confirmed staphylococcal associated CNS infection and treated with vancomycin or linezolid were included. Failure of antimicrobial
The Effectiveness and Safety of Bedaquiline, Pretomanid, and Linezolid (BPaL)-Based Regimens for Rifampicin-Resistant Tuberculosis in Non-Trial Settings-A Prospective Cohort Study in Belarus and Uzbekistan. Only 63% of patients initiating multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment in 2020 were treated successfully. 24-Week all-oral bedaquiline, pretomanid , and linezolid (BPaL)-based regimens have demonstrated higher rates of treatment success and have been recommended by the World Health Organization. Operational research is urgently required to evaluate these regimens in non-trial settings. This was a prospective cohort study of patients with microbiologically confirmed MDR/RR-TB and pre-extensively drug-resistant TB (pre-XDR-TB) initiated on BPaL-based
The optrA, cfr(D) and vanA genes are co-located on linear plasmids in linezolid- and vancomycin-resistant enterococcal clinical isolates in Italy. To characterize the optrA-, cfr(D)- and vanA-carrying linear plasmids detected in three MDR enterococcal clinical isolates. Enterococcus faecium (868), E. faecium (1001) and Enterococcus faecalis (2048), which were linezolid- and vancomycin-resistant due to the presence of optrA, cfr(D) and vanA genes, were tested for their susceptibility to several antibiotics. Characterization of the genetic elements carrying antibiotic resistance genes and ST determination were achieved using WGS data. The plasmid topology was evaluated by S1-PFGE. Resistance gene transferability was assessed by filter-mating experiments. The linezolid- and vancomycin
Unravelling the genetic contributors to linezolid resistance in Mycobacterium smegmatis: insights from a transposon library. This study aimed to identify and characterize genes associated with linezolid resistance in Mycobacterium smegmatis using a transposon mutagenesis approach. This research conducted three replicative experiments where 16 isolates displaying pronounced resistance to linezolid were examined, revealing two distinct morphologies. WGS was employed to investigate these isolates, uncovering mutations in specific genes. The binding affinity of linezolid to relevant proteins was assessed through molecular docking studies and validated by drug affinity responsive target stability (DARTS) assays. Complementation of the mspA gene in mutant strains restored linezolid
Effectiveness, safety, and pharmacokinetics of linezolid in pediatric bacterial central nervous system infections. Linezolid shows therapeutic potential for pediatric gram-positive bacterial central nervous system infections (CNSIs). However, its efficacy, safety profile, and cerebrospinal fluid (CSF) pharmacokinetics require detailed evaluation. This prospective two-center observational study enrolled children with confirmed or suspected gram-positive CNSIs. Clinical outcomes and adverse events were compared between linezolid-treated patients and a matched vancomycin cohort. Population pharmacokinetic (PopPK) modeling with nonlinear mixed-effects analysis quantified linezolid exposure in plasma and CSF. Among 45 matched pediatric CNSIs patients per group, linezolid demonstrated a 91.1
Safety and Tolerability of a Short Course of Linezolid for the Treatment of Predominantly Moderate to Severe Tuberculous Meningitis in Adults with HIV. Tuberculous meningitis (TBM)-related deaths occur early, often within weeks after initiation of treatment. Enhanced treatment early in the disease course with agents that effectively penetrate the central nervous system may improve outcomes in TBM. We conducted a phase 2, open-label, randomized trial in Masaka, Uganda to assess the safety and tolerability of linezolid 1200 mg versus no linezolid with high (35 mg/kg/day) or standard-dose (10 mg/kg/day) rifampin for 4 weeks in participants with definite or suspected TBM. The primary endpoint was any >grade 3 adverse event during the interventional period. Secondary endpoints included
Clinical efficacy of linezolid in the treatment of tuberculous meningitis: a retrospective analysis and literature review. Tuberculous meningitis (TBM) is the most severe form of tuberculosis, with high morbidity and mortality. This retrospective study evaluates the clinical efficacy of linezolid in patients with TBM. We analyzed 99 TBM patients treated at the Shanghai Public Health Clinical Center from June 2013 to March 2020. Patients were divided into two groups: those receiving standard therapy (n = 43) and those receiving standard therapy plus linezolid (n = 56). Clinical outcomes, cerebrospinal fluid parameters, and adverse events were assessed. Of the included patients, 42.4% were female, and the median age was 24.00 (7.00-44.00) years. Baseline characteristics between the two
Population pharmacokinetics and clinical assessment of linezolid in pediatric bacterial infections. The pharmacokinetic profile of linezolid still needs further definition, and insufficient or excessive exposure may lead to treatment failure or development of adverse events. Our study aimed to establish a population pharmacokinetic (PPK) model for linezolid in children with bacterial infections , develop an optimal dosage, and evaluate its efficacy and safety. A total of 157 plasma samples from 80 patients were utilized in PPK modeling. A one-compartment model with first-order elimination was most suitable for describing the PK characteristics of linezolid. Weight and creatinine clearance were the significant covariates for clearance. The outcomes of Monte Carlo revealed that in children under
Impact of hepatic impairment and renal failure on the pharmacokinetics of linezolid and its metabolites: contribution of hepatic metabolism and renal excretion. Linezolid, an oxazolidinone antibiotic, is used in patients with liver or kidney disease. However, the effects and mechanisms of hepatic impairment or renal failure on the pharmacokinetics of linezolid and its metabolites (PNU-142586 and PNU-142300) remain unclear. We used carbon tetrachloride-induced impaired hepatic function and 5/6 nephrectomy-induced renal failure rat models to investigate linezolid and metabolite pharmacokinetics. Isolated primary rat hepatocytes were used to evaluate the impact of hepatic impairment or renal failure on linezolid metabolism. Uptake and efflux transport studies were also conducted. The influence
Effect of linezolid on platelet count in critically ill patients with thrombocytopenia. Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia
Treatment of multidrug-resistant or rifampicin-resistant tuberculosis with an all-oral 9-month regimen containing linezolid or ethionamide in South Africa: A retrospective cohort study. In 2019, the South African tuberculosis program replaced ethionamide with linezolid as a part of an all-oral 9-month regimen. We evaluated treatment outcomes for patients assigned to regimens including linezolid in 2019 and ethionamide in 2017. This retrospective cohort study included patients treated for multi-drug resistant/rifampicin-resistant tuberculosis throughout South Africa between 1 Jan to 31 Dec 2017 and from 1 Jan to 31 Dec 2019. The cohort treated with a 9-month regimen containing ethionamide for four months, was compared with a cohort treated with a 9-month regimen containing linezolid for two
Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA. To investigate the global distribution of an optrA-harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage. Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed exhibited a high degree of or complete identity to the chromosomal transposon Tn6674. Only three isolates displayed an optrA-carrying plasmid with complete or partial Tn6674. The WT OptrA protein was most widespread in the ST476 lineage. Linezolid-resistant optrA-carrying E. faecalis of the clonal lineage ST476 is globally distributed in human, animal and environmental settings. The presence
Cost-effectiveness of linezolid to ventilator-associated pneumonia in Colombia. Ventilator-associated pneumonia (VAP) is a prominent cause of morbidity and mortality in intensive care unit (ICU) patients. Due to the increase in Methicillin resistant Staphylococcus aureus infection, it is important to consider other more effective and safer alternatives compared to vancomycin. This motivates evaluating whether the use of an apparently more expensive drug such as linezolid can be cost-effective in Colombia. A decision tree was used to simulate the results in terms of the cost and proportion of cured patients. In the simulation, patients can receive antibiotic treatment with linezolid (LZD 600 mg IV/12 h) or vancomycin (VCM 15 mg/kg iv/12 h) for 7 days, patients they can experience events