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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

Clinical efficacy and safety of linezolid in intensive care unit patients

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Journal of Intensive Medicine 2023年第1期3卷 65-72页

作者： Aijia Ma Meiling Dong Jiangli Cheng Xuelian Liao Wei Dong Chang Liu Chenggong Hu Jing Yang Yan Kang Department of Critical Care Medicine West China Hospital of Sichuan UniversityChengduSichuan 610041China

Background:To characterize the population of critically ill patients and infections treated with linezolid in the intensive care unit(ICU),and to evaluate the clinical efficacy and safety of linezolid ***::This multi-center,observational,real-world study was conducted across 52 hospitals between June 9,2018,and December 28,*** who met the following inclusion criteria were included:(1)admitted to the ICU,(2)of any age group,and(3)having a clinical or laboratory diagnosis of a Gram-positive bacterial *** efficacy was categorized as success(cured or improved),failed,or *** events and serious adverse events were recorded during ***::A total of 366 ICU patients who met the inclusion criteria were *** was used as second-and first-line treatment in 232(63.4%)and 134(36.6%)patients,*** most common isolated strain was Staphylococcus aureus(methicillin-resistant Staphylococcus aureus:n=37/119,31.1%;methicillin-susceptible Staphylococcus aureus:n=15/119,12.6%);this was followed by Enterococci(vancomycin-resistant Enterococci:n=8/119,6.7%;vancomycin-susceptible Enterococci:n=11/119,9.2%)and Streptococcus pneumoniae(multidrug-resistant:n=4/119,3.4%;non-multidrug resistant:n=2/119,1.7%).The main infection sites where pathogens were detected included the lung(n=216/366,59.6%),skin and soft tissue(n=104/366,28.4%),and blood(n=50/366,13.7%).Clinical success was achieved in 301(82.2%)patients;34(9.3%)were cured and 267(73.0%)improved;treatment failure and non-evaluable outcomes were observed in 29(7.9%)in 36(9.8%)patients,***-related adverse events were reported in 8(2.2%)*** treatment-related serious adverse events were ***::Based on real-world results,linezolid was found to be effective and safe in the treatment of Gram-positive bacterial infections in critically ill patients.

关键词： Intensive care unit linezolid Real-world study Gram-positive bacterial infection

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by linezolid Therapy in Hemodialysis Patients?

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Pharmacology & Pharmacy 2016年第10期7卷 417-423页

作者： Hideo Kato Mao Hagihara Yuka Yamagishi Yukihiro Hamada Jun Hirai Naoya Nishiyama Yusuke Koizumi Katsuhiko Matsuura Hiroshige Mikamo Department of Infection Control and Prevention Aichi Medical University School of Medicine Nagakute Japan Department of Pharmacy Aichi Medical University School of Medicine Nagakute Japan

Previous study suggested that low body weight was one of the risk factors of thrombocytopenia induced by linezolid in non-hemodialysis patients. However, there have been little investigations for the linezolid-induced thrombocytopenia in hemodialysis patients. This study was to evaluate the association between several factors of body size descriptors and thrombocytopenia in hemodialysis-patients. No factor of body size descriptors showed significant correlation with linezolid-induced thrombocytopenia (patients with thrombocytopenia vs patients without thrombocytopenia: body weight;60.0 kg vs 55.3 kg, p = 0.82: body mass indices;21.1 kg/m2 vs 21.2 mg/m2, p = 0.44: ideal body weight;61.2 kg vs 59.5 kg, p = 0.21: lean body weight;50.1 kg vs 45.7 kg, p = 0.64: dosage amount;20.0 mg/kg vs 21.7 mg/kg, p = 0.74: body surface area;1.65 m2 vs 1.54 m2, p = 0.43). There were not significant differences in the body size descriptors between linezolid therapy for more than 14 days and for less than 13 days (more than 14 days vs less than 13 days: body weight;53.5 kg vs 56.8 kg, p = 0.75: body mass indices;20.9 kg/m2 vs 21.1 mg/m2, p = 0.47: ideal body weight;60.3 kg vs 59.9 kg, p = 0.17: lean body weight;44.3 kg vs 47.7 kg, p = 0.56: dosage amount;22.4 mg/kg vs 21.1 mg/kg, p = 0.67: body surface area;1.51 m2 vs 1.59 m2, p = 0.37). Our data suggested that dosage adjustment of linezolid based on body weight was not recommended in hemodialysis-patients.

关键词： linezolid Thrombocytopenia Body Weight

Assessment of absolute oral bioavailability of linezolid tablets in Chinese healthy male volunteers

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Assessment of absolute oral bioavailability of linezolid tab...

中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： SHI Yao-guo ZHANG Jing YU Ji-chen CAO Guo-yin ZHANG Yin-yuan Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai 200040,China

AIM:linezolid is a member of oxazolidinones,which is a novel class of *** study is to determine the absolute bioavailability of linezolid tablets in Chinese healthy male volunteers. METHODS:A randomized,open cross-over study was conducted in 22 healthy male volunteers,a single oral dose of 600 mg linezolid tablets or Ⅳ infusion of 600 mg linezolid were given to subjects,*** sam- ples were obtained at different time points and sent to American AvTech *** concentrations of linezolid were determined by high-performance liquid chro- matography(HPLC),pharmacokinetic parameters and ab- solute bioavailability were calculated. RESULTS:After oral and IV infusion administration of 600 mg linezolid,the elimination half-life(t)was(4.3 +1.0)h and(4.4±0.9)h,*** area un- der plasma concentration-time curve(AUC)of lin- ezolid were(87±20)μg·mL·h and(96±21) μg·mL·h,*** absolute oral bioavailabili- ty was 93%±23% following single oral dose of 600 mg linezolid *** of two one-sided t tests and 90% confidence interval showed that linezolid tablet and Ⅳ formulation are equivalent with respect to *** ad- verse event was found except one volunteer with transitory mild epigastric pain. CONCLUSION:linezolid tablets can be completely ab- sorbed;it is equivalent in extent of absorption to its Ⅳ formulation.

关键词： linezolid tablet bioavailability

Comparative Mutant Prevention Concentrations of linezolid and Vancomycin against Methicillin-Resistant Staphylococcus aureus and Characterization of the Selected Reduced Vancomycin Susceptibility Strains

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Comparative Mutant Prevention Concentrations of Linezolid an...

第二届中国临床微生物学大会暨微生物学与免疫学三江论坛

作者： Jian-hong Zhao Jing Li Su-ju Sun Hongbo Zhao Dong-yan Shi Ji-hong Li Xing Wang Xi Lu Xiao-lei Liu Wen-jie Song Qiang Ye Shu-min Zhang and Lei Shi Department of Clinical Laboratory Sciences Second Hospital of Hebei Medical University College of Public Health Hebei Medical University College of Light Industry and Food Sciences South China University of Technology Chinese National Institute for the Control of Pharmaceutical and Biological Products(NICPBP)

This study aimed to compare the ability of linezolid and vancomycin to prevent the clinical methicillin-resistant Staphylococcus aureus（MRSA）resistant mutant by determining mutant prevention concentration（MPC）.We further investigated the possible molecular mechanism associated with reduced vancomycin susceptibility in the mutant strains by molecular fingerprinting ***-six clinical MRSA isolates were enriched in broth,and the bacterial concentration was adjusted to 1010 CFU/mL for MPC ***-type strains and mutant strains selected by vancomycin during MPC determination were characterized by pulsed-field gel electrophoresis（PFGE）,Sau-PCR assay,denaturing gradient gel electrophoresis（DGGE）,scanning electron microscopy（SEM）,and transmission electron microscopy（TEM）.Our results showed that both linezolid and vancomycin might have great ability to restrict the selection of resistant mutants of *** had a narrower mutant selection window against the MRSA isolates than ***-PCR assay and PFGE revealed that pre-scanning and post-scanning strains selected by vancomycin during the experimental process of MPC had different DNA *** and SEM showed that the mutant strains had slightly thicker cell walls than the wild-type *** was used to probe for mutations in the graS gene,but no different banding patterns were observed on the electrophoretogram *** showed greater ability to restrict the selection of resistant mutants of MRSA than *** wild-type strains and mutant strains selected by vancomycin during the experimental process of MPC,there may be mutations in genes other than the graS gene or existence of other resistant mechanisms.

关键词： Mutant Prevention Concentration linezolid Vancomycin Methicillin-Resistant Staphylococcus aureus

Effects of quadruple antituberculous drugs in combination with linezolid and moxifloxacin on CSF cytology, NSE, NGF and its receptors in patients with refractory tuberculous meningitis

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Journal of Hainan Medical University 2018年第15期24卷 44-47页

作者： Qing-Liang Hu Lyu-Lang Zhang Fourth Department of Tuberculosis Chongqing Public Health Medical CenterChongqing 400036China First Department of Infectious Disease Chongqing Public Health Medical CenterChongqing 400036China

Objective: To investigate the effects of linezolid and moxifloxacin combined with quadruple antituberculosis drugs on CSF cytology, NSE (neuronal specific enolase), NGF(nerve growth facor) and its receptors, endothelin and its receptors and CRP (C reaction protein) in patients with refractory tuberculous meningitis. Method: A total of 56 patients were selected with tuberculous meningitis in our hospital from February 2014 to December 2017,randomly divided them into 2 groups, each group was 28 cases, set as the observation group and the control group, both groups were treated with quadruple antituberculosis drugs, the observation group was given ilinezolid on this basis, and the control group was combined with moxifloxacin, The course of treatment was 4 weeks, compared the levels of CSF cytology, NSE, NGF and NGF receptors, endothelin and endothelin receptors, and CRP after treatment in the two groups. Result:The CSF cytology, NSE, NGF and NGF receptors, endothelin and endothelin receptor, and CRP levels remained unchanged before treatment, the difference was not statistically significant. After treatment, the chloride and glucose levels in the observation group were higher than those before treatment and that of the control group, the protein, white blood cell count, and cerebrospinal fluid pressure levels were lower than before treatment and that of the control group, the difference was statistically significant;The NSE level in the observation group after treatment was lower than before treatment and that of the control group, the difference was statistically significant;After treatment, the levels of NGF and its receptors in the observation group were higher than those before treatment and that of the control group, and the levels of endothelin, and its receptor, CRP were lower than those before treatment and that of the control group, the difference was statistically significant. Conclusion:The use of linezolid in combination with quadruple antituberculosis drug

关键词： Refractory Tuberculous Meningitis linezolid Moxifloxacin Quadruple Antituberculosis CSF Cytology NSE NGF and NGF Receptors Endothelin and Endothelin Receptor

Monte Carlo simulation for evaluation of the efficacy of linezolid,tigecycline and vancomycin against MRSA in China

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Monte Carlo simulation for evaluation of the efficacy of lin...

加快转变医药发展方式，占领科学技术制高点——2011年中国药学大会暨第11届中国药师周

作者： Liang Beibei,Wang Rui,Bai Nan,Cai Yun Department of Clinical Pharmacology,General Hospital of Chinese People’s Liberation Army,28 Fuxing Road,Beijing,P.R.China

OBJECTIVE:To compare the pharmacodynamic potency of linezolid,tigecycline and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in ***:MIC determinations were performed for 250 MRSA *** exposure,measured as ratio of steady-state total drug area under the curve to MIC (AUC/MIC),was modelled via a 10000-subject Monte Carlo *** targets included an AUC MIC >82.9 for linezolid,AUC MIC >17.9 for tigecycline and AUC MIC >400 for ***:The cumulative fraction of response (CFR) against all MRSA isolates were 88% and 85% for linezolid and *** CFRs of vancomycin in young population and vancomycin in elderly population were 87%,98%,*** regimens of linezolid,tigecycline and vancomycin performed poorly(linezolid,tigecycline and vancomycin are likely to be effective agents against MRSA isolates in ***,their ability to achieve high bactericidal or bacteriostatic pharmacodynamic exposure will be dependent on the bacterial susceptibility.

关键词： linezolid Tigecycline Vancomycin MRSA Monte Carlo simulation

Developing an isotope dilution UHPLC-MS/MS method to quantify linezolid in human plasma: application to therapeutic drug monitoring

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Developing an isotope dilution UHPLC-MS/MS method to quantif...

2021第26届广东省药师周大会

作者： Yanping Guan Xiaoxia Yu Ying Wang Qinhai Li Dan Liang Hua Zhu Chuxiong Chen Boyu Dong Jiebin Ou Kaifeng Qiu Junyan Wu Department of Pharmacy Sun Yat-Sen Memorial Hospital Sun Yat-Sen University

Aim: To optimize clinical efficacy and reduce the drug-exposure-related toxicity of linezolid, whose concentrations show wide inter-variabilities, a simple and reliable quantitative assay for TDM is necessary. Results: A UHPLC-MS/MS assay has been established for determination of linezolid in human plasma and fully validated according to the FDA guidelines. After a simple, isotope-dilluted precipitation with methanol, the analytes were separated by a straightforward isocratic mode and the tandem mass spectrometry was conducted under the ESI+ mode fitted with SRM. The calibration curves proved acceptable linearity in the range of 0.1-30.0 ug/mL. Conclusion: The present assay is currently used in routine clinical practice, being applied to TDM and helps to optimize individual dosing regimens and manage adverse effects in ICU patients.

关键词： linezolid LC-MS/MS Therapeutic drug monitoring(TDM)

Efficacy of linezolid combination with fosfomycin in a catheter-related biofilm infection model caused by a Methicillin-resistant Staphylococcus aureus（MRSA） strain

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Efficacy of linezolid combination with fosfomycin in a cathe...

第十二届全国化疗药理学术研讨会

作者： Xu Liu Dong Chai Department of Pharmaceutical Care PLA General Hospital

Objective:To study the efficacy of linezolid combination with fosfomycin in MRSA catheter-related biofilm ***:Using an in vitro study to assess alone or combination of linezolid and fosfomycin in planktonic or biofilm,then the fractional inhibitory concentration index,time-kill curve in planktonic and viable bacterial counts in biofilm were *** the biofilm-infected rat model,the synergy efficacy of treatment with linezolid and fosfomycin on infection were ***:The combination of linezolid and fosfomycin showed significant synergistic effects against MRSA in *** the biofilm-infected rat model,as single agent or combination of these two agents not reduced the numbers of white blood cells,but the normal rate of white blood cells in combination agents were higher than single *** was a statistical difference that combination agents compared with single agent at viable bacterial counts in biofilm in ***:Combination of linezolid and fosfomycin not only showed a positive effect in vitro but also improved the therapeutic effect in a biofilm-infected rat model.

关键词： MRSA linezolid Fosfomycin Biofilm

linezolid:第一个应用于临床的噁唑啉酮类抗菌药

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国外医药（抗生素分册） 2001年第6期22卷 279-281页

作者：肖永红重庆医科大学附属第一医院重庆400016

恶唑啉酮类为全新化学合成抗菌药 ,通过抑制细菌蛋白质合成起始阶段发挥抗菌作用。第一个应用于临床的口恶唑啉酮类药物 linezolid对革兰氏阳性菌有较强抗菌活性 ,抗菌活性与细菌耐药性无关 ;具有良好药物动力学特征 ;临床实验证明 ,对... 详细信息

恶唑啉酮类为全新化学合成抗菌药 ,通过抑制细菌蛋白质合成起始阶段发挥抗菌作用。第一个应用于临床的口恶唑啉酮类药物 linezolid对革兰氏阳性菌有较强抗菌活性 ,抗菌活性与细菌耐药性无关 ;具有良好药物动力学特征 ;临床实验证明 ,对各种革兰氏阳性菌感染有良好疗效。

关键词：恶唑啉酮类药物 linezolid 抗菌活性临床疗效革兰氏阳性菌