Evaluation of endotoxin release and cytokine production induced by antibiotics in patients with Gram-negative nosocomial pneumonia

OBJECTIVE: To determine the plasma concentrations of lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in a homogeneous group of septic patients and to evaluate the effect of antibiotic treatment, imipenem or ceftazidime, on the release of lipopolysaccharide and cytokines. DESIGN: Prospective, randomized study. SETTING: Sixteen-bed multidisciplinary intensive care unit. PATIENTS: Twenty-four septic patients with documented Gram-negative nosocomial pneumonia. Controls were 20 patients admitted without sepsis and 20 healthy volunteers. INTERVENTIONS: Septic patients were randomized between imipenem and ceftazidime. Blood samples were collected before (0 hrs) and after (4 and 12 hrs) antibiotic treatment. Concentrations of lipopolysaccharide were measured by using the limulus assay, and cytokine concentrations were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed by Kruskal-Wallis test, Mann-Whitney U test, and Student's t-test. MEASUREMENTS AND MAIN RESULTS: The mean age was 48.5 +/- 19.5. The mean Acute Physiology and Chronic Health Evaluation II score was 18.4 +/- 4.5. Overall mortality rate was 45.4%. All septic patients showed significant higher concentrations of lipopolysaccharide (p <.001), tumor necrosis factor-alpha (p <.04), and interleukin-6 (p <.001) than the controls, but interleukin-1 beta was never detected. We did not find statistically significant changes in lipopolysaccharide or cytokine plasma concentrations over time within any of the two arms of the study (ceftazidime vs. imipenem). There were no statistically significant differences in lipopolysaccharide and interleukin-6 plasma concentrations between the two antibiotic treatments. Although tumor necrosis factor-alpha plasma concentrations were significantly higher in the group treated with ceftazidime compared with the group treated with imipenem at the baseline and 4 hrs later, these differences were not statistically significant after 12 hrs of initiation of both treatments. CONCLUSIONS: Patients with Gram-negative nosocomial pneumonia have high plasma concentrations of lipopolysaccharide, interleukin-6, and tumor necrosis factor-alpha, but the antibiotic therapy evaluated did not significantly modify these concentrations.     

系统性红斑狼疮患者外周血单核细胞HLA-DR的表达和IL-10水平的变化

目的探讨系统性红斑狼疮（SLE）患者外周血单核细胞人白细胞DR抗原（HLA-DR）表达和白细胞介素-10（IL-10）水平变化及其临床意义。方法应用双色荧光抗体标记流式细胞术检测SLE患者外周血单核细胞HLA-DR表达的阳性率及荧光强度,用酶联免疫吸附试验（ELISA）测定血浆中IL-10的水平。结果与正常对照组比较,稳定期、活动期SLE患者外周血单核细胞HLA-DR表达的阳性率和荧光强度均显著降低,而IL-10水平显著升高;活动期SLE组单核细胞HLA-DR的阳性率及荧光强度均显著低于稳定期（P均〈0．001）,而IL-10水平高于稳定期（P〈0．001）;活动期SLE重度组与中度组相比,单核细胞HLA-DR的阳性率及荧光强度均显著降低（P均〈0．001）,而IL-10水平显著升高（P〈0．001）。SLE患者单核细胞HLA-DR表达的阳性率和血清IL-10浓度与SLE活动指数（SLEDAI）积分均无相关性（P〉0．05）。结论单核细胞HLA-DR表达的降低、IL-10水平的升高与SLE的发生、发展有着非常密切的关系。     

脑卒中患者医院内获得性肺炎危险因素分析

目的探讨脑卒中患者医院内获得性肺炎的危险因素及防治措施。方法对我院2003-01-01~2004-12-31 1832例脑卒中住院患者进行调查统计分析。结果医院内获得性肺炎感染率为5.57%,其中脑出血、脑梗死患者感染率分别为7.72%(24/311)和5.13%(78/1521)。Logistic多因素分析提示,发生医院内获得性肺炎OR的大小依次是预防应用抗生素、气管插管、气管切开、昏迷、应用H2受体阻滞剂、糖尿病、住院天数、吞咽困难、慢性阻塞性肺病(COPD)、鼻饲胃管。结论住院天数、气管切开、气管插管、鼻饲胃管、糖尿病、COPD、昏迷、吞咽困难、应用H2受体阻滞剂和预防应用抗生素等10个因素为脑卒中患者医院内获得性肺炎的相关危险因素。提示在临床工作中应予重视并加强防护,减少医院内获得性肺炎的发生。     

Impact of nosocomial pneumonia on the outcome of mechanically-ventilated patients

: BACKGROUND: Nosocomial pneumonia (NP) is a common complication in mechanically-ventilated patients and is considered to be one of the most common causes of morbidity and mortality. However, assessment of the associated mortality is not staightforward as it shares several risk factors with NP that confound the relationship. The aim of this study was to evaluate the impact of NP on the mortality rate in an intensive care unit. During the study period (January-December 1995) all patients under mechanical ventilation for a period > 48 h (n = 314) were prospectively evaluated, and the prognostic factors of NP, which have been identified in previous studies, were recorded. RESULTS: Pneumonia was diagnosed in 82 patients. The overall mortality rate was 34% for patients with NP compared to 17% in those without NP. Multivariate analysis selected the following three prognostic factors as being significantly associated with a higher risk of death: the presence of multiple organ failure [odds ratio (OR) 6.71, 95% CI, P < 0.001]; the presence of adult respiratory distress syndrome (ARDS) (OR 3.03, 95% CI, P < 0.01), and simplified acute physiology score (SAPS)> 9(OR 2.89, 95% CI, P < 0.05). CONCLUSIONS: In mechanically-ventilated patients NP does not represent an independent risk factor for mortality. Markers of severity of illness were the strongest predictors for mortality.     

重症肺炎患者血清中IL-6和IL-10的水平与临床预后的相关性分析

目的 探讨重症肺炎患者血清中促炎细胞因子白介素6(IL-6)和抑炎细胞因子白介素10(IL-10)与其临床预后的关系,为临床治疗提供依据.方法 将65例患者根据病程第10天的临床转归,分为好转组(35例)和恶化组(30例).用放免法检测两组患者第1、5、10天血清中IL-6、IL-10的水平,记录临床肺部感染评分(CPIS).结果 两组患者血清中IL-6均呈现下降趋势,但好转组下降更明显(P＜0.05);好转组患者血清IL-10呈下降趋势,但恶化组患者IL-10则呈明显上升趋势(P＜0.05);恶化组的CPIS在病程中有上升趋势,显著高于好转组(P＜0.05).结论 动态检测血清中IL-6和IL-10,以及CPIS,可反映重症肺炎患者的临床预后,值得临床推广应用.     

Attenuated monocyte IL-10 production in glucose-6-phosphate dehydrogenase-deficient trauma patients

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the world's most common known human genetic polymorphisms, but the pathophysiology of the defect remains largely unknown. In the present study, we compared hematology parameters and ex vivo monocyte cytokine responses in non-deficient and G6PD-deficient trauma patients. Deficient and non-deficient, moderately injured, trauma patients exhibited similar hematology profiles at the time of hospital admission. In contrast to non-deficient patients, G6PD-deficient patients were anemic 2 days post-injury. Monocytes from deficient individuals produced 50% less interleukin 10 (IL-10) in response to LPS and >90% less IL-10 in response to PMA, compared with non-deficient patients, 2 days post-injury. The presence of phenylhydrazine-treated, opsonized, autologous RBC (OX-RBC), alone had no effect on IL-10 production by non-deficient or deficient monocytes, whereas IL-10 responses to lipopolysaccharide (LPS) were augmented by OX-RBC in both groups. However, IL-10 production was markedly lower by monocytes from G6PD-deficient than non-deficient patients after stimulation with LPS plus OX-RBC. TNF-alpha production following PMA was similar in deficient and non-deficient patients, and the differences following LPS or LPS plus OX-RBC stimulation were moderate between deficient and non-deficient samples. Interferon (IFN)-gamma production ex vivo was doubled by OX-RBC treatment alone, but it was not stimulated by LPS treatment. IFN-gamma production was similar in non-deficient and G6PD-deficient patients. These data suggest that the observed differences in IL-10 responses between G6PD-deficient and non-deficient patients are not attributable to differences in TNF-alpha or IFN-gamma production. Taken together, our data suggest that a reduction in the capacity to produce IL-10 may be an intrinsic characteristic of G6PD-deficient monocytes. An attenuated IL-10 production may be a contributing mechanism in the previously observed augmented inflammatory response in severely injured G6PD-deficient compared with non-deficient trauma patients.     

Antisense IL-10 abrogates the inhibitory effects of IL-10 production by transfected tumor cells

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a variety of downregulatory effects on immunologic and inflammatory processes. Ectopic tumor expression of IL-10 inhibited tumor growth, and local administration of antisense IL-10 significantly reversed the effects of IL-10 transfection in P815 mastocytoma. Tissue inhibitors of metalloproteinase (TIMPs) have been associated with decreased tumorigenesis and reduced metastasis, and TIMPs were increased in the region surrounding P815/IL-10 tumors and reduced in antisense IL-10-treated mice. In addition, the antisense IL-10 group had the largest tumor volume and poorest survival when compared with the P815/IL-10 control or sense groups. In summary, our data suggest that, in a mouse model, antisense IL-10 has substantive effects in reducing IL-10 translation and inhibiting IL-10-mediated TIMP upregulation, and, by doing so, allows IL-10-transfected mastocytoma to grow unchecked. Thus, ectopic tumor expression of IL-10 inhibits tumor growth, and antisense IL-10 administration in vivo reverses this protective effect.     

外科术后患者院内获得性肺炎的痰菌分布和耐药率分析

目的 对外科术后并发院内获得性肺炎(HAP)的患者痰菌菌株进行总结分析,发现其特点,供临床借鉴.方法 选择2005-01至今我院外科手术患者术后并发院内获得性肺炎284例,收集共1403株痰菌资料进行治疗分析.细菌室按常规方法进行细菌培养和鉴定,采用涂片扩散法(K-B法)测定细菌药物敏感性,按照美国临床实验室标准委员会(NCLLS)标准判断结果.结果 1403株细菌中,G-杆菌1222株(87.09%),其中铜绿假单胞杆菌442株(占G-36.17%),肺炎克雷伯杆菌271株(占G-22.17%),不动杆菌216株(占G-17.67%),大肠埃希菌154株(占G-12.60%),嗜麦芽窄食假单胞菌80株(占G-6.54%),阴沟肠杆菌59株(占G-4.82%);G+菌181株(12.9%),其中金黄色葡萄球菌103株(占G+56.9%),凝同酶阴性葡萄球菌78株(占G+43.1%).结论 碳青霉烯类抗生素仍是所测定17种抗菌药物中对肠道阴性杆菌和铜绿假单胞杆菌最强的一类抗生素.酶抑制剂联合制剂对一般重症感染具有和泰能相似的临床疗效.耐药球菌对其他抗生素均显示较高的耐药率,万古霉素及替考拉宁为耐药球菌的首选抗生素.     

脑梗塞患者医院内获得性肺炎危险因素探讨及对策

探讨脑梗塞患者医院内获得性肺炎危险因素及防治对策。对513例脑梗塞住院患者进行调查统计分析。医院内获得性肺炎84例,感染率为16.4%。高龄体弱、住院日、意识障碍、肺部疾病、气管切开、气管插管、使用呼吸机、鼻饲胃管、应用糖皮质激素与H2受体阻滞剂和预防应用抗生素是脑梗塞患者医院内获得性肺炎的危险因素,应引起高度重视。在临床治疗和护理过程中加强防护,减少医院内感染的发生。     

Diagnostic value of the blind brush in mechanically ventilated patients with nosocomial pneumonia

Objectives: To check on the accuracy of a new protected blind brush (BB) inserted through an endotracheal tube to collect respiratory secretions to be used in the diagnosis of nosocomial pneumonia (NP) in ventilated patients.Design: Prospective study of patients who had undergone both BB and plugged telescoping catheter via fiberoptic bronchoscopy (PTC-FB) sample collection sessions.Setting: Intensive Care Unit of a referral-based University HospitalPatients: All patients (n=37) mechanically ventilated for more than 3 days with clinical and radiological criteria of NP between July 1990 and March 1991.Interventions: Randomized BB and PTC-FB sample collection sessions carried out less than 30 min apart.Measurements and main results: The two sampling procedures resulted in similar findings with both cultures either negative or positive and identified the same organism and colonies in 31 patients (83.7%). Agreement was 90% when the patients with right or bilateral pulmonary infiltrates were grouped together and 100% when only the right field was considered. Complications arising from BB sampling were much lower than those from the conventional PTC-FB technique.Conclusions: Our results, pending confirmation by other prospective studies, indicate that BB sampling is useful in the diagnosis of NP in ventilated patients with radiological evidence of either right or bilateral pulmonary infiltrates and that it could stand in for PTC-FB in ICU settings where this procedure is not available.     

Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

Purpose  

The objective of this study is to assess the distribution of vancomycin minimum inhibitory concentrations (MICs) in methicillin-resistant Staphylococcus aureus (MRSA) isolates and evaluate the efficacy of vancomycin relative to vancomycin MICs in adult patients with MRSA nosocomial pneumonia.     

Diagnosis of nosocomial pneumonia in mechanically ventilated patients by the blind protected telescoping catheter

Objectives To demonstrate that blind insertion of the protected telescoping catheter (PTC-NB) through the orotracheal tube can provide reliable pulmonary samples for the diagnosis of nosocomial pneumonia (NP) in ventilated patients.Design We performed a random comparison between the protected telescoping catheter intoduced through a bronchofiberscope (PTC-B) and the PTC-NB to diagnose NP.Setting: A general intensive care unit of a University Hospital.Patients 40 consecutive patients on mechanical ventilation and with suspicion of NP. The diagnosis of NP was suspected by clinical and chest X-ray findings.Measurements and results NP was confirmed microbiologically in 26 (65%) patients and maintained in 8 patients by clinical and radiological criteria. PTC-NB confirmed the microbiological diagnosis of PN in 21 (80%) patients. The use of antibiotics prior taking respiratory samples reduced the sensitivity of PTC-NB and PTC-B from 100–74% and from 94–70% (p=0.001). Both techniques agreed in 24 of 33 (73%) patients but such agreement was better when PN was on the right lung. Two patients developed a self-limiting hemoptysis after the PTC-B procedure.Conclusions PTC-NB is as sensitive as specific as PTC-B for diagnosing PN in mechanically ventilated patients, being a much easier technique to use.     

Increased levels of serum sulfite in patients with acute pneumonia

Sulfite, a common air pollutant, is toxic for humans, causing hypersensitivity or chronic airway diseases. We previously reported that sulfite is actively produced from neutrophils by stimulation with bacterial endotoxin, lipopolysaccharide (LPS). We also found that the serum sulfite concentration is increased in a rat model of sepsis induced by systemic injection of LPS. However, information on sulfite metabolism in human inflammatory conditions is limited. In the current study, the serum concentration of sulfite was determined in 25 patients with acute pneumonia. Serum sulfite concentration in pneumonia patients was significantly higher than that in control subjects (3.75 +/- 0.88 vs. 1.23 +/- 0.48 microM, respectively, P < 0.05). Among 20 patients, serum sulfite was serially determined before and after antibiotic therapy. The levels of serum sulfite were significantly reduced during the recovery phase compared with those during the acute phase (1.34 +/- 0.56 vs. 3.65 +/- 0.92 microM, respectively, P < 0.05). Moreover, neutrophils obtained from three patients during the acute phase of pneumonia spontaneously produced higher amounts of sulfite in vitro than those obtained after recovery. There was a close positive correlation (r = 0.71, P < 0.05) between serum sulfite and C-reactive protein (CRP) in patients with pneumonia. Taken together, the current findings suggest that serum sulfite increases during systemic inflammation in humans. Activated neutrophils might be responsible, at least in part, for the up-regulation of sulfite. Given various biological effects reported previously, sulfite may act as a mediator in inflammation.     

Diagnostic and therapeutic management of nosocomial pneumonia in surgical patients: results of the Eole study

OBJECTIVE: To assess clinical, microbiological, and therapeutic features of nosocomial pneumonias in surgical patients. DESIGN: Prospective (October 1997 through May 1998), consecutive case series analysis of patients suspected of having pneumonia during the fortnight after a surgical procedure or trauma and receiving antibiotic therapy prescribed by the attending physician for this diagnosis. SETTING: A total of 230 study centers in teaching (n = 66) and nonteaching hospitals (n = 164) (surgical wards and intensive care units). PATIENTS: A total of 837 evaluable patients (mean age 61 +/- 18 yrs) including 629 intensive care unit patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The diagnostic and therapeutic procedures followed were based on guidelines. Antibiotics and any changes of therapy and duration of treatment were decided by the attending physician. The charts were reviewed by a panel of experts that classified the cases according to clinical, radiologic, and microbiological criteria (when available). The efficacy of treatment was evaluated over a 30-day period following the index episode. The patients were classified into three groups: definite pneumonia (n = 261), possible pneumonia (n = 392), or low-probability pneumonia (n = 184). Ventilator-acquired pneumonia was reported in 303 patients. Early onset pneumonia was reported in 512 cases. Microbiological sampling was performed in 718 patients, by bronchoscopy in 367 cases, recovering 450 organisms in 328 patients, including 94 polymicrobial specimens. High proportions of Gram-negative bacteria and staphylococci were cultured, even in early onset pneumonias. Antibiotic therapy was administered for 13 +/- 4 days, using monotherapy in 254 cases. Changes in the initial antibiotic therapy (135 monotherapies) were decided in 517 patients (including clinical failure or persistent infection, n = 171; organisms resistant to initial therapy, n = 177; pulmonary superinfection, n = 68). Death occurred in 180 patients, related to pneumonia in 53 cases. CONCLUSIONS: Nosocomial pneumonias in surgical patients are characterized by high frequency of early onset pneumonia, high proportion of nosocomial organisms even in these early onset pneumonias, and moderate mortality rate.     

肺心病医院内肺炎的临床特点及危险因素分析

目的探讨肺心病医院内肺炎的临床特点及危险因素。方法对我院1994年1月至2004年12月收治的400例肺心病患者中的31例医院内肺炎患者临床资料进行回顾性分析。结果肺心病医院内肺炎感染率为7．75％（31／400），死亡率为29．03％（9／31），主要病原菌为革兰氏阴性杆菌（67．74％）。结论肺心病医院内肺炎诊断主要依据胸部X射线检查和深部痰细菌培养。广谱抗菌素使用时间、类固醇激素使用时间、昏迷时间、气管切开或插管留置时间、低蛋白血症等是主要危险因素。