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Safety and clinical efficacy of linezolid in children:a systematic review and meta-analysis

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World Journal of Pediatrics 2023年第2期19卷 129-138页

作者： Yi Shi Hai-Lan Wu Yu-Hang Wu Shuang Li Li-Ya Zhang Shan-Shan Xu He-Yu Huang Chun-Hong Zhang Xu-Ben Yu Kang Cai Jing Zhang Li-Su Huang Department of Infectious Disease Xinhua Children’s HospitalXinhua HospitalShanghai Jiao Tong University School of MedicineShanghai200092China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou310052China Institute of Antibiotics Huashan HospitalFudan UniversityShanghai200040China Department of Pharmacy the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China

Background We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial *** A systematic literature search was conducted up to April 23,2021,using linezolid and its synonyms as search *** reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort *** extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects *** A total of 1082 articles were identified,and nine studies involving 758 children were included in the *** overall proportion of adverse events was 8.91%[95%confidence interval(CI)=1.64%–36.52%],with diarrhea(2.24%),vomiting(2.05%),and rash(1.72%)being the most *** incidences of thrombocytopenia and anemia were 0.68%and 0.16%,*** specific adverse events,including rash and gastrointestinal events,were more frequent in the oral administration *** terms of efficacy,the overall proportion of clinical improvement was 88.80%(95%CI=81.31%–93.52%).Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such *** proportion of microbial eradication was 92.68%(95%CI=84.66%–96.68%).The proportion of all-cause mortality was 0.16%(95%CI=0.00%–7.75%).Conclusions linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events,such as anemia,thrombocytopenia,and ***,linezolid was effective in children with diagnosed and suspected Gram-positive infections.

关键词： Children Efficacy linezolid Meta-analysis Safety

High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid

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Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 287-292页

作者： Yi-Min Zhang Wei Yu Ning Zhou Jian-Zhou Li Li-Chen Xu Zhong-Yang Xie Ying-Feng Lu Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Department of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

BACKGROUND： linezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of throm- bocytopenia in patients with acute-on-chronic liver failure （ACLF） who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocyto- penia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.

关键词： acute-on-chronic liver failure linezolid thrombocytopenia

A Convenient Synthesis of Antibacterial linezolid from (S)-Glyceraldehyde Acetonide

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Chinese Chemical Letters 2006年第3期17卷 302-304页

作者： Guang Yu XU Yi ZHOU Man Cai XU College of Chemistry and Chemical Engineering Hunan Normal University Changsha 410081

A convenient synthesis of oxazolidinone antibacterial linezolid from readily available L-ascorbic acid is described. The key steps include reductive amination of arylamine and （S）-glyceraldehyde acetonide in the pre... 详细信息

关键词： linezolid antibacterial synthesis ascorbic acid.

Daptomycin and linezolid for severe methicillin-resistant Staphylococcus aureus psoas abscess and bacteremia:A case report and review of the literature

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World Journal of Clinical Cases 2022年第8期10卷 2550-2558页

作者： Xiao-Bing Hong Ze-Lin Yu Hong-Bo Fu Ze-Hong Cai Jie Chen Department of Pharmacy The Second Affiliated Hospital of Shantou University of Medical CollegeShantou 515041Guangdong ProvinceChina Department of Pharmacology Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of Pharmacy The First Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510080Guangdong ProvinceChina

BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)***,a number of gram-positive cocci have developed resistance to several drugs,including ***,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant *** SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and *** tomography(CT)results showed an abscess in the psoas major muscle of the *** abscess drainage and blood culture suggested MRSA,and vancomycin was ***,after day 10,CT scans showed abscesses in the lungs and legs of the ***,treatment was switched to *** was also added considering inflammation in the *** 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for *** day 28,the patient was discharged without any *** This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.

关键词： Bacteremia Daptomycin Gram-positive cocci linezolid Methicillin-resistant Staphylococcus aureus Vancomycin Case report

A validated stability-indicating LC method for the separation of enantiomer and potential impurities of linezolid using polar organic mode

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Journal of Pharmaceutical Analysis 2012年第4期2卷 272-278页

作者： T.Satyanarayana Raju O.Vishweshwari Kutty V.Ganesh P.Yadagiri Swamy Dr.Reddy's Laboratories Ltd.Active Pharmaceutical Ingredients IPDOBachupallyHyderabad 500072A.PIndia Department of Chemistry University College of EngineeringOsmania University

Although a number of methods are available for evaluating linezolid and its possible impurities, a common method for separation if its potential impurities, degradants and enantiomer in a single method with good efficiency remain unavailable. With the objective of developing an advanced method with shorter runtimes, a simple, precise, accurate stability-indicating LC method was developed for the determination of purity of linezolid drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of linezolid along with the chiral impurity. This method can also be used for the estimation of assay of linezolid in drug substance as well as in drug product. The method was developed using Chiralpak IA (250 mm 4.6 mm, 5 mm) column. A mixture of acetonitrile, ethanol, n-butyl amine and trifluoro acetic acid in 96:4:0.10:0.16 (v/v/v/v) ratio was used as a mobile phase. The eluted compounds were monitored at 254 nm. linezolid was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability.

关键词： HPLC linezolid Validation Polar organic mode Stability-indicating

Clinical results of linezolid in arthroplasty and trauma related infections

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World Journal of Orthopedics 2014年第2期5卷 151-157页

作者： James Joel Simon Matthew Graham Adam Peckham-Cooper Nectarios Korres Helen Tsouchnica Eleftherios Tsiridis Academic Orthopaedic and Trauma Unit Leeds Teaching Hospitals Leeds School of Medicine Leeds LS1 3EX United Kingdom Royal Liverpool University Hospital Liverpool L7 8XP United Kingdom Academic Orthopaedics and Trauma Unit Division of Surgery Aristotle University Medical School University Campus 54 124 Thessaloniki Greece

AIM: To analyse the management of patients treated with linezolid for orthopaedic ***: Twenty-two patients with orthopaedic related infections receiving a course of linezolid were reviewed retrospectively. Patients were classified into either post trauma, post arthroplasty and non trauma related infections. A diagnosis of infection was based on clinical findings, positive microbiological specimens, and positive signs of infection on radiological imaging and raised inflammatory markers. Pathogens isolated, inflammatory markers both at presentation and at final follow up, length of linezolid treatment, adverse drug reactions, concomitant anti-microbial therapy, length of hospital stay and any surgical interventions were ***: Infections were classified as post arthroplasty(n = 10), post trauma surgery(n = 8) or nontrauma related infections(n = 4). Twenty patients(91%) underwent surgical intervention as part of their treatment. The number of required surgical procedures ranged from 1 to 6(mean = 2.56). Mean total length of stay per admission was 28.5 d(range 1-160 d). Furthermore, the mean duration of treatment with linezolid of patients who had resolution of symptoms was 31 d(range 10-84 d). All patients within this group were discharged on oral linezolid. Pathogens isolated included methicillin resistant Staphylococcus aureus, coagulase negative staphylococci, coliforms, enterococcus, Staphylococcus epidermidis, streptococcus viridans, Escherichia coli, group B streptococcus and pseudomonas. An overall 77% of patients demonstrated resolution of infections at follow-up, with mean C-reactive protein reducing from 123 mg/L to 13.2 mg/***: This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.

关键词： Antibiotic resistance linezolid Orthopaedic infections Osteomyelitis Periprosthetic joint infection

linezolid versus Vancomycin for the Treatment of Methicillin-Resistant <i>Staphylococcus aureus</i>in Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia at Tertiary Care Hospital

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Advances in Infectious Diseases 2017年第1期7卷 11-18页

作者： Eman Mohammad Hamdan Majda Al-Attas Yanbu General Hospital Ministry of HealthYanbuSaudi Arabia King Faisal Specialist Hospital and Research Centre JeddahSaudi Arabia

Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-associated pneumonia (HCAP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Retrospective analysis data. Data were collected for adult patients admitted to King Faisal Specialist Hospital and Research Centre-Jeddah (KFSH & RC-J) from January 2010 to May 2015. Method: A total of 88 patients with HAP, VAP and HCAP caused by MRSA treated with vancomycin (IV) or linezolid (IV or PO) either as empirically or directed therapy ≥ 7 days. They are retrospectively evaluated and analyzed. The primary end points are morbidity and mortality rate as well as clinical cure rate. The secondary end point is the cost analysis for each medication. Results: A total of 40 patients (ICU, n = 13 (32.5% and non ICU, n = 27 (67.5%)) were included in the study. Among vancomycin, n = 21 (52.5%);age (54.95 ± 18.255) and linezolid, n = 19 (74.5%);age (48.684 ± 25.593), there was no statistical differences in mortality and morbidity rate (P = 0.375). Clinical cure rate (fever improvement, 12 (57.1%) vs 12 (63.2%);P = 0.698, leukocytosis improvement, 15 (71.4%) vs 14 (73.7%);P = 0.873, purulent sputum improvement, 6 (28.6%) vs 4 (21.1%);P = 0.429, dyspnea improvement, 8 (38.1%) vs 3 (15.8%);P = 0.115,cough improvement 4 (19.0%) vs 4 (21.1%);P = 0.592, microbiological eradication of MRSA from sputum culture, 2 (9.5%) vs 6 (31.6%);P = 0.089 and improvement of radiographic finding (pulmonary infiltration), 17 (81.0%) vs 16 (84.2%);P = 0.559) of vancomycin vs linezolid, respectively. The cost analysis in the treatment of MRSA pneumonia with linezolid is statistical significantly higher than vancomycin. The mean cost of vancomycin = 185.9143 SR and of linezolid = 4547.3684 SR (P Conclusion: There are no statistical differences in mortality and morbidity rate and clinica

关键词： linezolid Vancomycin Pneumonia Methicillin-Resistant Staphylococcus aureu

Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci

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Chinese Medical Journal 2013年第14期126卷 2670-2675页

作者： WU Jing JIANG Tian-tong SU Jian-rong LI Li Department of Clinical Laboratory First Hospital of Fangshan District Beijing 102400 China Department of Clinical LaboratoryBeijing Friendship Hospital Capital Medical University Beijing 100050 China Division of Traditional Chinese MedicineBeijing Friendship Hospital Capital Medical University Beijing 100050 China

Background Vancomycin-resistant Enterococci （VRE） cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration （MPC） of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE. Methods The minimum inhibitory concentrations （MICs） of linezolid and minocycline against 30 Enterococci （E.） isolates （including 20 VRE strains） were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 （linezolid MIC, 2 g/ml; minocycline MIC, 4 tJg/ml） and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline （alone and combined） were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction （PCR） amplification of domain V of the 23S rRNA gene. Results Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed, The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa. Conclusion linezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.

关键词： linezolid minocycline Enterococcus mutation

The Prevalence of Methicillin-Resistant Staphylococcus aureus Colonization in Patients with Complicated Skin and Skin Structure Infections after Treatment with linezolid or Vancomycin

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Advances in Infectious Diseases 2014年第4期4卷 186-193页

作者： Laura A. Puzniak Kimbal D. Ford David B. Huang formerly Pfizer Inc. Collegeville USA Pfizer Inc. Collegeville USA

Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage has been a focus of infection control interventions. The prevalence of MRSA colonization after successful treatment of a MRSA cSSSI is unknown. Methods: Secondary analysis of a randomized controlled trial comparing linezolid and vancomycin for the treatment of MRSA cSSSI. Adult patients that had a colonization culture, confirmed MRSA cSSSI, received at least one dose of study treatment, and had an outcome recorded at end of study. Patient, clinical characteristics and prevalence of colonization were compared by treatment regimens. A multivariate regression model identified predictors of MRSA colonization at EOS. Results: There were 456 patients evaluated. The prevalence of MRSA colonization was higher for vancomycin treated patients compared to linezolid treated patients at end of treatment (EOT) (28% vs. 5%, p linezolid for a cSSSI had less MRSA colonization at EOT and EOS compared to those treated with vancomycin. Multiple independent predictors of MRSA colonization were identified. Additional studies evaluating the relationship of MRSA colonization after treatment of cSSSI are needed.

关键词： Staphylococcus aureus Complicated Skin and Skin Structure Infection Colonization linezolid