利奈唑胺治疗中性粒细胞减少血液病革兰阳性球菌感染76例临床分析

目的分析利奈唑胺治疗中性粒细胞减少血液病患者革兰阳性(G+)球菌感染的疗效和安全性。方法收集2008年8月至2009年5月苏州大学附属第一医院血液科收治的76例中性粒细胞减少疑诊G+球菌感染血液病患者,以利奈唑胺600 mg,每日2次抗感染治疗,从临床表现和病原学方面评价其疗效,同时观察药物不良反应。结果 76例患者总有效率为91.26%。单用利奈唑胺组有效率92.31%;混合感染初始即联合利奈唑胺组有效率92.59%;混合感染初始联合其他抗G+菌药物后换用利奈唑胺组有效率88.89%。3组病例体温控制中位时间分别为3.313、.76及6.58 d。恶性血液病不缓解、长期使用广谱抗生素及合并G-菌感染是影响利奈唑胺疗效的3个重要因素。利奈唑胺不良反应发生率为26.31%,发生肝功能轻度异常患者未予停用利奈唑胺,经保肝治疗后肝功迅速恢复,其余患者均予以停药后3 d至2周后患者。结论利奈唑胺治疗粒细胞减少血液病患者G+菌感染具有明显疗效。轻症感染或病原学检查提示明确G+菌感染病例,针对性单药利奈唑胺即可取得明显疗效。重症混合感染首选联合利奈唑胺者疗效优于利奈唑胺作为二线药物者。恶性血液病完全缓解、避免广谱抗生素长期使用和及时有效病原体检查有助于利奈唑胺发挥抗G+菌感染的疗效。利奈唑胺引发的不良反应较少。     

利奈唑胺和万古霉素对革兰阳性球菌肺炎治疗效果的荟萃分析

目的 采用荟萃分析方法对现已发表的利奈唑胺和万古霉素治疗革兰阳性球菌肺炎的文献进行综合分析,评价利奈唑胺的疗效及其安全性是否优于万古霉素.方法 检索Medline数据库、Embase数据库、Ovid数据库、Cochrane图书馆及中文生物医学期刊数据库中的相关文献.检索年限均从建库到2009年2月,并查阅所有纳入文献的参考文献.外文检索词包括linezolid、glycopeptides、vancomycin、pneumonia、gram-positive cocci、saureus、MRSA、enterococcus及streptococci.限定语言为中文或英文,限定对象为"人".中文检索词为相应的主题词.纳入用英文或中文发表的比较利奈唑胺和万古霉素治疗革兰阳性球菌肺炎疗效的随机对照试验,由2名评价员独立筛查文献、评价质量和提取资料.采用Jadad量表及随机分配方案隐藏方法评估纳入研究的方法学质量;采用x2检验鉴定研究间的异质性,使用随机效应或固定效应模型合并研究;采用敏感性分析方法探讨研究结果的影响因素.结果共纳入7个随机对照研究,包括1425例革兰阳性球菌肺炎患者.荟萃分析结果显示,利奈唑胺治疗结束后在临床可评估患者的临床治愈率优于万古霉素(OR=2.16,95%CI为1.13～4.16,P<0.05);随访结束后,临床可评估患者(OR=1.11,95%CI为0.81～1.53,P>0.05)及意向性治疗患者(OR=1.01,95%CI为0.78～1.31,P>0.05)利奈唑胺的临床治愈率、微生物学总治愈率(OR=1.31,95%CI为0.85～2.04,P>0.05)、金黄色葡萄球菌清除率(OR=1.45,95%CI为0.84～2.51,P>0.05)、耐甲氧西林金黄色葡萄球菌清除率(OR=1.36,95%CI为0.51～3.61,P>0.05)、链球菌清除率(OR=4.27,95%CI为0.01～1365.87,P>0.05)及肠球菌清除率(OR=0.75,95%CI为0.03～17.51,P>0.05)与万古霉素相同.利条唑胺治疗组与万古霉素治疗组的病死率(OR=0.80,95%CI为0.59～1.07,P>0.05)及不良反应总体发生率(OR=1.06,95%CI为0.68～1.64,P>0.05)比较差异无统计学意义.结论 对革兰阳性球菌肺炎患者,利奈唑胺虽在治疗刚结束时的临床疗效优于万古霉素,但1～4周随访结束后,两组临床疗效无明显差异.     

利奈唑胺治疗老年髓系白血病患者合并革兰阳性球菌感染的疗效

目的探讨利奈唑胺治疗老年白血病化疗后患者合并革兰阳性(G+)球菌感染的临床疗效。方法选择54例老年白血病(≥60岁)确诊G+球菌感染患者,随机分为治疗组26例,对照组28例,对照组常规抗感染治疗,治疗组在对照组的基础上,加用利奈唑胺治疗对比两组的临床治疗效果。结果经抗感染治疗,治疗组总有效率(92.31%)高于对照组(64.29%)(P<0.05);治疗组的平均用药时间〔(8.19±2.08)d〕短于对照组〔(11.85±2.75)d〕(P<0.05)。结论利奈唑胺治疗老年白血病患者合并G+菌感染的疗效显著,安全性高。     

利奈唑胺和替考拉宁治疗住院高龄革兰阳性菌感染患者的临床应用分析

目的调查和比较利奈唑胺和替考拉宁治疗住院高龄革兰阳性球菌感染患者的疗效和安全性。方法回顾性分析2008年1月至2011年8月我科住院的高龄革兰阳性球菌感染患者的临床资料,共58例[年龄84-98岁,平均（91．2±4．0）岁],分为利奈唑胺组（30例）和替考拉宁组（28例）,设定临床疗效评价（痊愈、显效、进步、无效）和细菌学疗效评价标准（清除、假设清除、未清除,替换、再感染）,了解利奈唑胺和替考拉宁的疗效和不良反应。结果临床总有效率利奈唑胺组为93．3％,替考拉宁组为78．5％,二者无统计学差异（P=0．103）;细菌清除率利奈唑胺组为86．7％,明显高于替考拉宁组的53．6％（P〈0．05）。治疗过程中利奈唑胺组主要不良反应为血小板减少,替考拉宁组主要不良反应为血肌酐升高。结论利奈唑胺和替考拉宁在临床上治疗高龄革兰阳性球菌感染患者疗效肯定,利奈唑胺在临床疗效和细菌清除率方面优于替考拉宁。在选择用药时,要严格掌握适应证。需注意监测血小板和血肌酐的变化。     

利奈唑胺治疗腹腔感染1例报告

1 病历资料 患者男,39岁,因"反复发作上腹痛6年,加重5 d"于2007-11-29入院.患者自述2001-2007年"胆囊炎"和"急性胰腺炎"多次发作,均经内科治疗后好转.5 d前因劳累及饮酒后再发腹痛,在外院查血尿淀粉酶增高,经内科治疗不能缓解,逐渐出现腹压增高、血压下降、少尿症状,遂在外院急诊行"胰腺松解术,胃、空肠、胆囊造瘘术".     

利奈唑胺血清药物浓度监测在耐药结核病患者中的应用

利奈唑胺是一种新型的?唑烷酮类抗生素,是治疗耐药结核病的关键药物,该药治疗窗口狭窄,虽然疗效明显,但是临床应用不良反应的发生率高,如何安全有效地应用该药治疗耐药结核病一直困扰临床医生。治疗药物监测（therapeuticdrugmonitoring,TDM）通过监测患者血液中的药物浓度,可为药物剂量调整提供依据,使药物达到有效治疗浓度的同时最大程度地降低不良反应发生。目前国内外均有报道利用TDM研究利奈唑胺在耐药结核病患者中的最佳使用剂量和疗程,探讨利奈唑胺的谷浓度、峰浓度与不良反应发生率之间的关系,特别是对老年人、儿童、肝肾功能不全的患者临床安全使用利奈唑胺个体化治疗进行系列的探索研究。本文对利奈唑胺不良反应的发生机制、利奈唑胺的使用剂量及安全性、利奈唑胺药物浓度的影响因素、TDM的方式和应用等进行综述,为更加安全有效地应用利奈唑胺治疗耐药结核病提供参考。     

利奈唑胺治疗难治性胆道感染1例报告

1 病历资料 患者男,83岁,因"头晕、恶心、呕吐半个月,加重伴发热半天"于2008-03-17入院.半个月前无明显诱因出现恶心、头昏、呕吐胃内容物.口服药物治疗效果不佳(药物不详),半天前症状突然加重并伴有发热达39℃.到我院急诊,查白细胞16.8×109/L(中性粒细胞0.13),血红蛋白145 g/L,血小板计数109×109/L.     

利奈唑胺治疗ICU重症感染27例

目的探讨利奈唑胺在ICU重症感染患者中应用的有效性及安全性。方法对入住ICU的27例重症感染患者给予利奈唑胺0.6 g,2次/d,观察用药前和用药72 h后的体温、血常规、肝肾功能等指标的变化并进行对比分析,以评价药物的有效性及安全性。结果 27例患者中19例好转,8例死亡或自动出院,临床有效率为70.37%。使用利奈唑胺72 h后,患者体温血象均较前下降,血小板计数稍有下降,肝肾功能无明显变化,所观察的指标治疗前后差异无统计学意义(P0.05)。结论利奈唑胺在重症感染患者中短期应用是安全有效的,长期应用的药物副作用需要进一步观察。     

利奈唑胺对肺部革兰氏阳性细菌感染患者肾功能的影响

利奈唑胺是新型的恶唑烷酮类抗菌药,对革兰氏阳性细菌有很强的抗菌作用,与其它抗菌药无交叉耐药性。我们观察了利奈唑胺对患者肾功能的影响,并与万古霉素进行比较。     

利奈唑胺治疗广泛耐药结核病的临床疗效评价

目的评价利奈唑胺治疗广泛耐药结核病的临床疗效。方法我院收治的24例广泛耐药结核病患者,随机分为两组,对照组12人采用常规化疗,试验组12人加用利奈唑胺,比较不良反应和疗效。结果试验组试验组症状改善、病灶吸收、空洞闭合、抗酸染色涂片阴性、痰结核分枝杆菌阴性、痰定量PCR阴性例数均明显高于对照组,试验组不良反应发生率高于对照组,差异均有统计学意义（P〈0.05）,经对症治疗后均痊愈。结论利奈唑胺治疗广泛耐药结核病疗效显著。     

Mixed Infection in Adult Bacterial Meningitis

Summary 12 adult patients suffering from bacterial meningitis caused by mixed infection were identified at Kaohsiung Chang Gung Memorial Hospital over a period of 13 years (1986–1998), and they accounted for 6.5% (12/184) of our culture-proven adult bacterial meningitis. The 12 cases included seven males and five females, aged 17–74 years. Six of the 12 cases had community-acquired infections and the other six had nosocomially-acquired infections. Ten of the 12 cases had associated underlying diseases, with head trauma and/or neurosurgical procedure being the most frequent. Both gram-negative and gram-positive pathogens were identified in these 12 cases with gram-negative pathogens outnumbering the gram-positive ones. The implicated pathogens, starting with the most frequent, included Enterobacter species (Enterobacter cloacae, Enterobacter aerogenes), Klebsiella species (Klebsiella pneumoniae, Klebsiella oxytoca), Escherichia coli, Staphylococcus species (Staphylococcus aureus, Staphylococcus haemolyticus), Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus, Serratia marcescens, Citrobacter diversus, Proteus mirabilis, Streptococcus viridans and Neisseria meningitidis. Six of the 12 cases were found to have multi-antibiotic-resistant strains, which included E. cloacae in one, A. baumannii in one, K. pneumoniae in one and S. aureus in three. The management of these 12 cases included appropriate antibiotics and neurosurgical procedures including shunt revision. Despite the complexity of implicated pathogens and the high incidence of emergence of resistant strains, the overall mortality rate (8.3%, 1/12) was not higher than that in adult bacterial meningitis. However, complete recuperation was difficult in adult patients with mixed bacterial meningitis. Received: October 5, 1999 · Accepted: November 23, 1999     

Linezolid versus glycopeptide or beta-lactam for treatment of Gram-positive bacterial infections: meta-analysis of randomised controlled trials

Linezolid has been approved for the treatment of patients with infections caused by Gram-positive cocci that are resistant to traditionally used antibiotics, including glycopeptides. This oxazolidinone antibiotic has been reported to have excellent pharmacokinetics and effectiveness. We did a meta-analysis of randomised controlled trials (RCTs) to clarify whether linezolid is superior to glycopeptides or beta-lactams for the treatment of Gram-positive infections. 12 RCTs, involving 6093 patients, were included. Overall, with respect to treatment success, linezolid was more effective than glycopeptides or beta-lactams (odds ratio [OR] 1.41 [95% CI 1.11-1.81]). Mortality was similar between the groups (OR 0.97 [0.79-1.19]). Linezolid was more effective than comparators in patients with skin and soft-tissue infections (OR 1.67 [1.31-2.12]) and bacteraemia (OR 2.07 [1.13-3.78]). However, there was no difference in treatment success for patients with pneumonia (OR 1.03 [0.75-1.42]). Treatment with linezolid was not associated with more adverse effects in general (OR 1.40 [0.95-2.06]); however, thrombocytopenia was recorded more commonly in patients receiving linezolid (OR 11.72 [3.66-37.57]). Although linezolid is more effective than its comparators for the empirical treatment of selected patients, several points, such as the use of less potent antistaphylococcal beta-lactams, the same all-cause mortality, and the higher probability of thrombocytopenia, should be taken into account and may limit the use of linezolid to specific patient populations or infections that are difficult to treat with other antibiotics.     

The Coagulation Mechanism in Acute Bacterial Infection

Successive coagulation studies were performed in 34 adult patients hospitalized for treatment of acute bacterial infection. Increased fibrinogen, factor-VIII activity, and platelets were found in more than 50% of the patients studied. Classical disseminated intravascular coagulation occurred in three cases. Nine patients had elevated fibrin split products in various combinations with transient hypofibrinogenaemia, thrombocytopenia, and reduced factor-V activity. The appearance of elevated fibrin split products together with transient hypofibrinogenaemia, thrombocytopenia, and reduced factor-V activity in some patients may reflect the presence of subclinical disseminated intravascular coagulation.     

Bacterial Infection in Cirrhosis, with and without Hepatocellular Carcinoma

Objective: The extent and type of bacterial infection occurring with liver cirrhosis has remained unknown. Further, while hepatocellular carcinoma (HCC) is known to occur mainly in patients with liver cirrhosis, no report has yet investigated the incidence of bacterial infection in HCC. The purpose of the present study was to establish the prevalence of bacterial infection in patients with HCC. Methods : We have retrospectively investigated all 1140 patients with hepatic cirrhosis and/or HCC for any incidence of bacterial infection. Results : The incidence of bacterial infection was found to be 15.4%. in 740 patients with HCC. This was approximately equal to the incidence of bacterial infection in 400 patients with cirrhosis without HCC, which was found to be 15.3%. When the severity of cirrhosis was graded according to Child-Pugh classification, the incidences of bacterial infection in Child-Pugh class A. class B, and class C were 3.3%, 11.1%, and 31.2%, respectively, in cirrhosis, and 2.3%, 9.1%, and 25.6% in HCC The incidence of bacterial infection increased with the severitv of cirrhosis and severe bacterial infections occurred in Child-Pugh class B and C patients. Conclusion : The data suggest that the susceptibility of HCC patients to bacterial infection is mainly related to the underlying cirrhosis and not to the HCC.     

Identification of Concurrent Bacterial Infection in Adult Patients with Dengue

We aim to construct a diagnostic model for bacterial coinfection in dengue patients (Dengue Dual Infection Score [DDIS]); 2,065 adult dengue patients (mean age = 41.9 ± 17.2 years, 58.4% male, 83 patients with bacterial coinfection) seen at a university hospital from January of 2005 to February of 2010 were studied. The DDIS was created by assigning one point to each of five risk factors for bacterial coinfection: pulse rate ≥ 90 beats/minute, total white cell count ≥ 6 × 10⁹/L, hematocrit < 40%, serum sodium < 135 mmol/L, and serum urea ≥ 5 mmol/L. The DDIS identified bacterial coinfection (derivation set area under the curve = 0.793, 95% confidence interval = 0.732–0.854; validation set area under the curve = 0.761, 95% confidence interval = 0.637–0.886). A DDIS of ≥ 4 had a specificity of 94.4%, whereas a DDIS of ≥ 1 had a sensitivity of 94.4% for bacterial coinfection. The DDIS can help to select dengue patients for early bacterial cultures and empirical antibiotics.     

Bacterial Colonization and Beta Defensins in the Female Genital Tract in HIV Infection

Beta defensins are antimicrobial peptides that serve to protect the host from microbial invasion at skin and mucosal surfaces. Here we explore the relationships among beta defensin levels, total bacterial colonization, and colonization by bacterial vaginosis (BV)-related bacteria and lactobacilli in the female genital tract in HIV infected women and healthy controls. Cervicovaginal lavage (CVL) samples were obtained from 30 HIV-infected women and 36 uninfected controls. Quantitative PCR assays were used to measure DNA levels of bacterial 16S ribosomal DNA (reflective of total bacterial load), and levels of three BV-related bacteria, three Lactobacillus species (L. crispatus, L. iners and L. jensenii), and total Lactobacillus levels in CVL. Levels of human beta defensins (hBD-2 and hBD-3) were quantified by ELISA. In viremic HIV+ donors, we found that CVL levels of bacterial 16S rDNA were significantly increased, and inversely correlated with peripheral CD4+ T cell counts in HIV+ women, and inversely correlated with age in both HIV+ women and controls. Although CVL DNA levels of BV-associated bacteria tended to be increased, and CVL levels of Lactobacillus DNAs tended to be decreased in HIV+ donors, none of these differences was significant. CVL levels of hBD-2 and hBD-3 were correlated and were not different in HIV+ women and controls. However, significant positive correlations between hBD-3 levels and total bacterial DNA levels in controls were not demonstrable in HIV+ women; the significant positive correlations of hBD2 or hBD-3 and three Lactobacillus species in controls were also not demonstrable in HIV+ women. These results suggest that HIV infection is associated with impaired regulation of innate defenses at mucosal sites.