Linezolid:第一个应用于临床的噁唑啉酮类抗菌药

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 。

Linezolid——一种新噁唑烷酮类抗微生物药物

噁唑烷酮类药物是一类新的抗微生物制剂,在体外实验和动物感染模型实验中,此类药对革兰氏阳性菌(抗生素敏感的和耐药的)有很强抗菌活性。临床试验证实Linezolid口服给药的相对生物利用度为100％,噁唑烷酮类与其它抗生素无交叉耐药,且通过抑制细菌蛋白质合成的早期阶段而起作用。实验未筛选出耐药突变种。

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

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.

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

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.

Clinical results of linezolid in arthroplasty and trauma related infections

AIM: To analyse the management of patients treated with linezolid for orthopaedic infections.METHODS: 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 recorded.RESULTS: 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/L.CONCLUSION: This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.

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

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 presence of NaBH4 and 4A sieve, followed by hydrolysis and regioselective cyclization.

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

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

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

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 < 0.001) and EOS (34% vs. 22%, p < 0.01). Independent predictors of colonization at EOS after treatment for a MRSA cSSSI included diagnosis, primarily driven by abscess, black race, treatment with vancomycin, MRSA mixed infection and male gender. Conclusion: Patients treated with 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.

新型噁唑烷酮类抗菌药——Linezolid的药理及临床评价

目的:介绍新型(口恶)唑烷酮类抗菌药——Linezolid(LNZ)。方法:综述LNZ的药理作用、药动学特性、适应证、用法、用量、不良 反应以及与其它药物的相互作用等情况。结果与结论:LNZ可治疗多种耐药菌感染,且在临床应用中的耐受性良好,具有广阔的应 用前景。

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

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.

Linezolid resistant Staphylococcus haemolyticus:First case report from India

Linezolid is being increasingly used in the treatment of infections with gram-positive organisms especially methicillin resistant Staphylococcal isolates.Though resistance to this antimicrobial is emerging but it is extremely rare.Here we document first case of linezolid resistant Staphylococcus haemolyticus(S.haemolyticus) from India.This organism was isolated from pus oozing from a postsurgical site in 61 year old male hailing from an adjoining state of Haryana.

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

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 drugs to treat refractory tuberculous meningitis has better clinical effect, effectively improve cerebrospinal fluid cytology, regulate cerebrospinal fluid NSE levels, restore NGF, endothelin and its receptor function, reduce inflammatory response, recommended for clinical promotion and application.

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

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 clinical cure rate between linezolid and vancomycin in the treatment of MRSA in HAP, VAP, and HCAP. However, the cost of linezlid is significantly higher than vancomycin during the treatment period of one patient.

01062 Linezolid在皮肤和软组织感染中获得好评

根据九、十月份在美国波士顿召开的美国感染性疾病协会年会上提交的研究结果，复杂的皮肤和软组织感染患者使用Zyvox(linezolid)(Ⅰ)治疗比用万古霉素(varcomycin)(Ⅱ)治疗可导致更高的治愈率和较低的保健费用。

口服linezolid治疗皮肤感染明显减少花费

在美国感染性疾病协会（IDSA）第43届年会上发表的一项研究结果表明，与万古霉素相比，最初口服linezolid（Ⅰ）治疗皮肤感染可显著减少美国医疗系统花费。