肺炎链球菌对大环内酯类抗生素耐药机制研究

目的观察耐大环内酯类肺炎链球菌的耐药表型和基因型。方法用琼脂二倍稀释法测定耐大环内酯类肺炎链球菌对11种抗生素的最低抑菌浓度,耐药表型由红霉素和克林霉素双纸片法初步分型,通过PCR扩增耐药基因ermB和mefA进行基因分型,并测定ermB和mefA基因序列。结果　所有23株肺炎链球菌对大环内酯和克林霉素高度耐药,均表现为内在型耐药,没有发现诱导型耐药和M型耐药。ermB基因在23株肺炎链球菌中均检测到,其中5株同时检测到mefA基因,没有发现仅单一mefA基因阳性的菌株,基因型与耐药表型完全一致。所测ermB和mefA基因序列与基因库收录序列高度一致。 结论ermB基因介导的靶位改变可能是重庆地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。     

大肠埃希菌、肺炎克雷伯菌的耐药性变迁

目的了解大肠埃希菌、肺炎克雷伯菌对抗生素耐药性变迁. 方法采用纸片扩散确认试验和双纸片协同试验,药敏试验采用纸片扩散法. 结果 4年中大肠埃希菌、肺炎克雷伯菌超广谱β-内酰氨酶(ESBLs)的发生率呈逐年上升的趋势.从1999～2002年大肠埃希菌、肺炎克雷伯菌总的ESBLs菌的发生率分别为15.9%、14.8%、20.2%、29.6%;产ESBLs菌对氨基糖苷类、喹诺酮类和磺胺类交叉耐药,且呈逐年上升趋势;产ESBLs菌株70%发生于重症监护病房. 结论实验室应尽早开展ESBLs的检测,合理使用抗生素,有效控制ESBLs的传播和流行.     

医院获得性肺炎克雷伯菌性肺炎患者脂质过氧化损伤的研究

目的探讨医院获得性肺炎克雷伯菌性肺炎患者体内的氧自由基损伤. 方法对呼吸加强病房20例医院获得性肺炎克雷伯菌性肺炎患者血清脂质过氧化氢(LHP)水平、血清谷胱甘肽过氧化物酶(GSH-PX) 及血清3种超氧化物歧化酶(SOD)进行测定, 并与对照组进行比较. 结果克雷伯菌性肺炎组LHP明显高于健康对照组, 两组比较差异非常显著(t=7.8901, P<0.01);GSH-PX水平明显低于对照组, 两组比较差异非常显著(t=9.9810, P<0.01);SOD T、SOD Cu-Zn、SOD Mn水平明显低于对照组, 两组比较差异非常显著(t=7.8546, t=10.3378, t=5.2179, 均P<0.01). 结论医院获得性肺炎克雷伯菌性肺炎患者体内存在由自由基介导的脂质过氧化损伤,这种脂质过氧化损伤参与了肺炎克雷伯菌性肺炎的病理过程;在治疗中合理使用自由基清除药物可能提高临床疗效.     

大肠埃希菌、克雷伯菌产超广谱β-内酰胺酶的检测及耐药性分析

目的研究本院3年中大肠埃希菌、克雷伯菌ESBLs的检出率及对常用抗生素的耐药情况。方法对山西医科大学第二医院2001～2003年分离的837株大肠埃希菌、216株克雷伯菌用标准纸片扩散确证法检测其ESBLs产生率；采用K-B法进行药敏检测。结果大肠埃希菌产ESBLs分离率为2001、2002、2003分别为12．27％、15．90％、30，85％；克雷伯菌产ESBLs分离率为2001、2002、2003分别为23．88％、28．81％、30．00％；产ESBLs株对头孢菌素类、氨基糖苷类、氟喹喏酮类耐药率均高于非产ESBLs菌株；未发现对亚胺培南耐药的菌株。结论近年来大肠埃希菌、克雷伯菌产ESBLs菌株逐年升高，应引起足够的重视，采取有效措施控制产ESBLs菌的感染。     

重症监护病房肺炎克雷伯菌临床特点及耐药分析

目的 分析重症监护病房（ICU）肺炎克雷伯菌感染的临床特点及耐药情况,为临床合理使用抗菌药物提供依据。方法 回顾性分析重庆医科大学附属第一医院2014年1月～2016年12月ICU肺炎克雷伯菌感染病例483例,药敏试验采用纸片扩散法,双纸片协同试验进行超广谱β内酰胺酶检测,WHONET5.6及SPSS 21.0软件统计分析数据。结果 ICU肺炎克雷伯菌感染常见于伴多种易患因素的老年患者,下呼吸道为主要感染部位;CREKp感染死亡率高,多合并感染性休克或多器官功能障碍。3年来ICU检出肺炎克雷伯菌对常用抗菌药物耐药率不同程度上升,特别是CREKp菌株分离逐渐增加且呈泛耐药特点,仅对替加环素、米诺环素敏感。结论 ICU肺炎克雷伯菌感染发病率高且病情重,CREKp感染死亡风险高,应充分认识其严重性。治疗上依据药敏试验结果指导临床选择适当抗菌药物尤为重要。     

How cost effective is switching universal vaccination from PCV10 to PCV13? A case study from a developing country

BackgroundChildren immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children.MethodsA complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13. Epidemiological information on PCV10 impact was obtained from lab-based epidemiological surveillance on pneumococcal isolates at the Colombian National Institute of Health. Economic inputs were extracted from the literature. Incremental PCV13 effectiveness was based in additional serotypes included. Comparisons among alternatives were evaluated with the Incremental Cost-Effectiveness Ratio (ICER) at a willingness to pay of one GDP per capita (USD$ 6631) per Year of Live Saved (YLS). All costs were reported in 2014USD. Deterministic and probabilistic sensitivity analyses were performed, and 95% confidence interval reported.ResultsAfter four years using PCV10 for universal vaccination on children the Colombian health surveillance system showed a relative increment on non PCV10 isolates. To change from PCV10 to PCV13 would avoid 587 (CI95% −49–1008) ambulatory Rx community-acquired pneumoniae (CAP), 1622 (CI95% 591–2343) Inpatient RxCAP, 10 (CI 95% 6–11) pneumococcal meningitis, and 79 (CI95% 76–98) deaths. ICER per YLS was USD$ 2319 (CI95% Dominated – USD$ 4225) for Keep-PCV10 and USD$ 1771 (CI95% USD$ 1285–9884) for Switch-to PCV13. In spite of its cost-effectiveness Keep-PCV10 is an extended dominated alternative and Switch-to PCV13 would be preferred. Results are robust to parameters changes in the sensitivity analyses.ConclusionA national immunization strategy based in Switch-to PCV13 was found to be good value for money and prevent additional burden of pneumococcal disease saving additional treatment costs, when compared with to Keep-PCV10 in Colombia, however additional criteria to decision making must be taken into account.     

Apoptosis driven infection

Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and macrophages (MF) kill pathogens as the first line of defense. These cells possess numerous effector mechanisms to eliminate a threat at first contact. However, several microorganisms still manage to evade phagocytic killing, survive and retain infectivity. Some pathogens have developed strategies to silently infect their preferred host phagocytes. The best example of an immune silencing phagocytosis process is the uptake of apoptotic cells. Immune responses are suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of their plasma membrane. Taking Leishmania major as a prototypic intracellular pathogen, we showed that these organisms can use the apoptotic “eat me” signal PS to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way, enable the intracellular survival of the viable parasites. Subsequently these pathogens again use PS exposition, now on infected PMN, to silently invade their definitive host cells, the MF. In this review, we will focus on L. major evasion strategies and discuss other pathogens and their use of the apoptotic “eat me” signal PS to establish infection.     

Pneumonia‐induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters

The aim of the present work is to provide a better comprehension of the pneumonia‐induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF‐α and IL‐1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS‐2 expression appeared late after bacteria inoculation, whereas levels of NOS‐1 and NOS‐3 were unchanged. The high NOS‐2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae‐induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.     

绍兴地区肺炎链球菌的血清型和耐药性

目的:调查绍兴地区流行肺炎链球菌的血清型和耐药性,对不同来源的菌株进行比较,计算PCV7的覆盖率,为临床用药提供指导。方法:收集105株不同样本来源的肺炎链球菌,使用Pneumotest-latex鉴定血清型,统计耐药性,并研究两者之间关系。结果:105株肺炎链球菌,青霉素不敏感仅1株咽拭子分离菌,红霉素、克林霉素耐药率为99.3%,未检到万古霉素、左氧氟沙星耐药株,复方SMZ、四环素、利福平、氯霉素的耐药率分别为77.9%、86.2%、5.1%、10.6%。主要检出的血清组/型为19和23,占所有菌株的47.6%(49/103),PCV疫苗覆盖率为62.1%。结论:不同样本来源的肺炎链球菌的流行血清型和耐药性差异有统计学意义,眼部分离肺炎链球菌较其他部位分离株耐药程度低,PCV7覆盖率低,需长期监测。     

Adult K lebsiella pneumoniae meningitis in Qatar: clinical pattern of ten cases

ObjectiveTo describe the clinical presentation, underlying diseases, antimicrobial susceptibility, treatment and outcome of Klebsiella pneumoniae meningitis patients.MethodsThis retrospective study involved all patients with 15 years of age or older who admitted to Hamad General Hospital with culture proven Klebsiella pneumoniae meningitis from January 1, 2007 to December 31, 2012.ResultsA total of ten cases were identified (nine males and one female). Their mean age was (43.3±12.8) years. Eight patients (80%) had nosocomial meningitis with neurosurgery being the most frequent associated condition. Fever and altered consciousness were the most frequent symptom. Cerebrospinal fluid showed elevated protein and glucose levels. Gram stain showed Gram-negative rods in 50% of cases, while positive cerebrospinal fluid culture results were found in all patients. Multidrug resistance was observed in two cases, and all patients had received appropriate empirical and definitive antibiotic treatments. The mean duration of intravenous antimicrobial treatment was (19.3±7.0) d and all patients with external ventricular drains underwent removal of the device, while in-hospital mortality was 50%.ConclusionsThe number of cases was too small to come up with therapeutic and prognostic conclusions. Further large-scale prospective study is needed.