高龄患者呼吸机相关性肺炎危险因素的探讨

【摘要】目的：探讨呼吸机相关性肺炎（VAP）在≥80岁年龄患者中危险因素。方法：回顾性分析在ICU接受有创机械通气≥48h 167例患者的临床资料,按VAP将167例患者分为VAP组（49例）和非VAP组（118例）,比较两组发病特点、危险因素及相关变量的差异。结果：167例机械通气患者中发生VAP49例;相关变量的单因素检验有10个变量为VAP的危险因素,经过Logistic回归分析仍保留的危险因素有：机械通气时间、其他部位医院感染、多器官功能不全。结论：在ICU中高龄老人VAP发生与多种因素有关,主要有机械通气时间、其他部位医院感染、多器官功能不全。     

Multiple granulomas in three squirrel monkeys (Saimiri sciureus) caused by Mycobacterium microti

Mycobacterium microti, a member of the Mycobacterium tuberculosis complex, causes tuberculosis in small rodents and occasionally in other mammals including man. Three adult male squirrel monkeys, two with a history of lethargy, weakness and stridor and one with paralysis of the hind legs, were presented for necropsy. One of the two lethargic animals showed multiple granulomas in the mesentery, mesenteric lymph nodes, lung, liver, kidneys and spleen, while the other showed granulomas only in the lung. The animal with paralysis of the legs had an abscess-like lesion in the skeletal muscle of the neck, granulomas in the mesenteric and mediastinal lymph nodes, and a fracture of the thirteenth thoracic vertebra with severe lesions of the spinal cord. Histologically the granulomas showed typical features of tuberculous granulomas, i.e., central necrosis surrounded by epithelioid cells, multinucleated giant cells, inflammatory cells and a border of connective tissue. Ziehl-Neelsen stain demonstrated sporadic acid-fast bacilli within the granulomas, these organisms being identified as M. microti by microbiological and molecular methods.     

Salmonella-induced SipB-independent cell death requires Toll-like receptor-4 signalling via the adapter proteins Tram and Trif

Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island-1 protein SipB whereas delayed cell death is independent of SipB and occurs 18-24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram-negative bacteria and is recognized by Toll-like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB-independent cell death through Toll-like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram(-/-) and Trif(-/-) BMDM proliferate in response to Salmonella infection.     

Bacterial DNA Induces the <Emphasis Type="Italic">Complement</Emphasis> System Activation in Serum and Ascitic Fluid from Patients with Advanced Cirrhosis

Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with bacterial DNA. Group III included patients with spontaneous bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous bacterial peritonitis and may occur in an endotoxin-independent manner.     

非HIV感染患者肺孢子菌肺炎合并急性呼吸衰竭16例诊疗分析

目的 提高对非HIV感染患者肺孢子菌肺炎（PCP）合并急性呼吸衰竭的诊断和治疗的认识。方法 对2015年1月—2017年12月我院重症监护科收治的16例非人类免疫缺陷病毒（HIV）感染的肺孢子菌肺炎合并急性呼吸衰竭患者的临床表现、实验室检查、影像特点、治疗及转归等临床资料进行总结及讨论。结果 15例患者在发病前存在激素或免疫抑制剂使用史,均以发热和干咳、呼吸困难为首发症状后病情进展迅速。患者均存在呼吸衰竭［氧合指数（85.8±16.8）mmHg］,有创呼吸机辅助呼吸11例,高流量氧疗5例。胸部CT主要表现为弥漫性磨玻璃影。支气管肺泡灌洗液六胺银染色阳性2例,肺孢子菌PCR检测阳性16例。16例患者应用复方磺胺甲噁唑（SMZco）联合卡泊芬净与激素治疗,8例痊愈,7例死亡,1例放弃治疗后死亡。入住ICU时间为3~29 d,平均（13.0±7.1）d。结论PCP是应用免疫抑制剂患者易患的机会性感染,对于重症PCP患者SMZco联合卡泊芬净与激素治疗效果良好。     

Shortened Courses of Antibiotics for Bacterial Infections: A Systematic Review of Randomized Controlled Trials

Commonly prescribed durations of therapy for many, if not most, bacterial infections are not evidence‐based. Misunderstandings by clinicians and patients alike influence perspectives on antibiotic use, including duration of therapy and its role in antibiotic resistance. To demonstrate that shorter durations of antibiotic therapy are as efficacious as longer durations for many infections, a systematic review was undertaken of English‐language articles by using PubMed to identify articles for inclusion. Additionally, infection‐specific guidelines were identified for review of recommendations. Search terms included specific infection types, randomized controlled trial (RCT), duration of therapy, treatment duration, short course, and long course. Only RCTs of single‐agent antibiotic therapy for the treatment of bacterial infections in adults were included. Independent data extraction of articles was conducted by two authors by using predefined guidance for article inclusion. In total, 23 RCTs met our criteria for inclusion. All trials compared single‐agent antibiotics for a short and long antibiotic course in six common infections: community‐acquired pneumonia, ventilator‐associated pneumonia, intraabdominal infections, skin and soft tissue infections, uncomplicated cystitis, and complicated cystitis or pyelonephritis. Clinicians can decrease net antibiotic use by recommending shorter courses where evidence supports them. Antimicrobial stewardship programs that systematically address treatment duration may significantly affect institutional antibiotic use without negatively affecting patient care.     

老年呼吸机相关肺炎患者死亡的危险因素

目的分析老年呼吸机相关肺炎(VAP)患者死亡的危险因素。方法调查2011年4月—2017年2月某院年龄≥60岁且发生VAP的患者,收集患者的临床资料,包括基本情况、感染情况、预后等,并对其死亡的危险因素进行分析。结果共有老年VAP患者682例,198例患者死亡,病死率为29.03%。APACHEⅡ评分15分(OR=2.482,95%CI=1.473~4.183)、机械通气时间15 d(OR=2.526,95%CI=1.661~3.840)、多重耐药菌感染(OR=3.379,95%CI=2.008~5.686)、真菌感染(OR=3.414,95%CI=1.830~6.370)、使用糖皮质激素(OR=2.075,95%CI=1.265~3.403)、血清清蛋白浓度35 g/L(OR=2.129,95%CI=1.386~3.268)、器官损伤数目≥3个(OR=3.438,95%CI=2.165~5.459)、血糖≥10 mmol/L(OR=1.744,95%CI=1.106~2.751)等8个因素均为老年VAP患者死亡的独立危险因素。结论老年VAP患者死亡与多种因素有关,临床应采取以干预主要危险因素为主的综合防控措施,降低其病死率。     

Early administration of appropriate antimicrobial agents to improve the outcome of carbapenem-resistant Acinetobacter baumannii complex bacteraemic pneumonia

Carbapenem-resistant Acinetobacter baumannii complex (CRABC) is an emerging pathogen that causes bloodstream infections and nosocomial pneumonia. This study aimed to describe severe infection associated with CRABC bacteraemic pneumonia and to investigate risk factors for 28-day mortality. All patients aged ≥18 years with CRABC bacteraemic pneumonia were enrolled retrospectively at five teaching hospitals in South Korea. Empirical antimicrobial therapy was defined as appropriate if administration of at least one antimicrobial agent, to which the causative pathogen was susceptible, for >48?h, within 5 days of the onset of bacteraemia. During the study period, 146 patients with CRABC bacteraemic pneumonia were enrolled. Among them, 128 (87.7%) patients were treated in the intensive care unit; of these, 110 (75.3%) had ventilator-associated pneumonia. A total of 42 patients (28.8%) received appropriate empirical therapy. There was no difference in baseline characteristics between the appropriate and inappropriate empirical treatment groups. However, 28-day mortality was higher in the inappropriate therapy group (54.8% vs. 76.9%; P?=?0.008). Multivariate Cox regression analysis revealed that Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥20 [hazard ratio (HR)? =?1.28, 95% confidence interval (CI) 1.04–1.58; P?=?0.02], septic shock (HR?=?3.49, 95% CI 2.15–5.67; P?<0.001) and inappropriate empirical therapy (HR?=?3.24, 95% CI 1.94–5.42; P?<0.001) were independently associated with an adverse outcome. In conclusion, the mortality rate of CRABC bacteraemic pneumonia was extremely high. Appropriate empirical therapy might improve the outcome of patients with CRABC bacteraemic pneumonia.     

Is gentamicin safe and effective for severe community-acquired pneumonia? An 8-year retrospective cohort study

Gram-negative bacilli are the causative organisms in a significant proportion of patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU). Clinical guidelines recommend broad-spectrum antimicrobials for empirical treatment despite alarming global trends in antimicrobial resistance. In this study, we aimed to assess the safety and efficacy of gentamicin, an aminoglycoside with potent bactericidal activity, for empirical Gram-negative coverage of severe CAP in patients admitted to the ICU. A retrospective cohort study was performed at a university teaching hospital where the severe CAP guideline recommends penicillin, azithromycin and gentamicin as empirical cover. Ceftriaxone plus azithromycin is used as an alternative. Adults with radiologically-confirmed severe CAP were included, comparing those who received gentamicin in the first 72?h of admission with those who did not. Participants were identified using ICD-10 codes for bacterial pneumonia and data manually extracted from electronic medical records. Of 148 patients admitted with severe pneumonia, 117 were given at least one dose of gentamicin whereas the remaining 31 were not. The two groups were well matched in terms of demographics, co-morbidities and disease severity. There were no significant differences between the gentamicin and no-gentamicin groups in the incidence of acute kidney injury [60/117 (51%) vs. 16/31 (52%), respectively], hospital mortality [20/117 (17%) vs. 7/31 (23%)] and secondary outcomes including relapse and length of hospital stay. In conclusion, gentamicin is safe and has similar outcomes to alternative Gram-negative antimicrobial regimens for empirical coverage in severe CAP patients admitted to the ICU.     

Preclinical evaluation of potential infection‐imaging probe [68Ga]Ga‐DOTA‐K‐A9 in sterile and infectious inflammation

The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N?‐tetraacetic acid (DOTA) conjugated peptide [⁶⁸Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [⁶⁸Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [⁶⁸Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose ([¹⁸F]FDG). The scans showed that [⁶⁸Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [⁶⁸Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [⁶⁸Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.