Cefquinome-loaded microsphere formulations against Klebsiella pneumonia infection during experimental infections

The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7?mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8?±?3.6?μm). The encapsulation efficiency and drug loading of cefquinome were 91.6?±?2.6% and 18.7?±?1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1β and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.     

Current and future treatment options for community-associated MRSA infection

Introduction: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia.

Areas covered: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic.

Expert opinion: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.     

Pharmacological interventions for stress ulcer prophylaxis in critically ill patients: a mixed treatment comparison network meta-analysis and a recursive cumulative meta-analysis

Background: Proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RA), sucralfate and antacids are the commonly administered agents for stress ulcer prophylaxis (SUP) in critically ill patients. The authors of this paper have conducted a network meta-analysis to compare the efficacy of these agents in SUP.

Methods: Electronic databases were searched for randomized controlled trials, cohort studies and conference abstracts for studies comparing a SUP agent in critically ill patients to another active SUP agent or placebo. Overt, occult and clinically significant upper gastro-intestinal (UGI) bleeding, all-cause mortality, pneumonia, gastric colonization and ICU length of stay were considered as the outcome measures. A random effects model was used to generate pooled estimates.

Results: A total of 53 studies (4258 participants) were included. The pooled estimates were in favor of PPI and sucralfate for the overt UGI bleeding. PPI and H2RA bolus were associated with increased risk of gastric colonization and pneumonia.

Conclusions: SUP in critically ill patients was not associated with any benefit with regard to clinically significant bleeding episodes. However, PPI and sucralfate significantly reduces overt UGI bleeding. On the contrary, PPI and H2RA bolus are associated with an increased risk of gastric colonization and pneumonia.     

婴幼儿肺炎支原体肺炎的临床特点及预后分析

目的分析婴幼儿肺炎支原体肺炎(MPP)的临床特点及预后,发现区别并为其早期识别提供理论依据。方法选取2013年2月-2017年5月在宁海县第一医院儿科住院治疗的诊断为婴幼儿MPP的80例患儿,根据年龄分为<1岁组(20例)和1~3岁组(60例)。记录患儿的临床表现,进行特异性肺炎支原体(MP)-Ig M检测。比较两组患儿的临床表现、实验室检查结果及肺外并发症发生率。结果两组患儿发热发生率、热峰、热程,喘鸣音发生率,血常规结果,胸片检查结果比较差异均有统计学意义(均P<0.05)。两组患儿肺外并发症发生率、治愈率比较差异均无统计学意义(P>0.05)。逐步回归分析发现:入院时体温、肺外并发症及血清MP-Ig M抗体滴度对住院天数有显著影响(均P<0.05)。结论与幼儿期相比,婴儿期对炎症刺激反应较弱,应针对MPP婴幼儿做到早期迅速诊断,进行有效治疗,防止疾病蔓延造成不良后果。     

V4 region of the HIV-1 envelope gene mediates immune escape and may not promote the development of broadly neutralizing antibodies

To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p.i.) was identified from a cohort of HIV negative men who have sex with men. The coevolution of the viral envelope gene and nAbs was studied over 741 days p.i. Strain-specific antibodies (ss-Abs) to the transmitted/founder (T/F) virus developed within 54 days p.i., but plasma collected at subsequent time points could not neutralize synchronous viruses until 557 days p.i., when the plasma acquired low-level synchronous but not heterologous neutralizing activity. The V4 region of envelope gene mutated firstly and continually evolve up to 2 years p.i. Multiple variations in the V4 region, including substitutions, deletions and glycosylation mutations, were driven by ss-Abs and mediated immune escape partially by impacting the binding of nAbs to the virus. The remarkable variations in the V4 region mediated immune escape from ss-Abs and contributed to the affinity maturation of ss-Abs against the T/F virus but may not promote the development of bnAbs. Thus, the V4 region might not be a good target for an HIV-1 vaccine.     

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network)

BackgroundOngoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons.MethodsThe Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death.ResultsOverall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4–48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4–47.8%) and 48.0% (95% CI: 37.5–56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8–65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0–88.4%).ConclusionsWhile effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability.ClinicalTrials.gov Identifier: NCT01517191.     

Incidence of all-cause adult community-acquired pneumonia in primary care settings in France

Objectives

To estimate the incidence of all-cause outpatient community-acquired pneumonia (CAP) in adults in France from a national prospective observational study of CAP management in general practice (CAPA).

儿童血清维生素A、D、E水平与肺炎支原体肺炎相关性的临床研究

目的 研究儿童血清维生素A、D、E水平与肺炎支原体肺炎的相关性,为临床防治提供指导。方法 选取肺炎支原体肺炎住院治疗患儿415例为支原体肺炎组,儿保科非呼吸道感染儿童431例为对照组。分别检测两组儿童血清维生素A、D、E水平。结果 支原体肺炎组血清维生素A、D、E平均值均明显低于对照组(P<0.01);维生素A缺乏例数明显高于对照组(P<0.01),亚临床维生素A缺乏例数与对照组相比差异无统计学意义(P>0.05);维生素D缺乏及不足例数均明显高于对照组(P<0.01);维生素E缺乏例数明显高于对照组(P<0.01)。结论 维生素A、D、E缺乏与肺炎支原体肺炎的发病相关,特别是缺乏维生素A,补充维生素A、D、E有可能对预防肺炎支原体肺炎反复发作有益,其具体机制有待于进一步探讨。     

血清25-(OH)D3水平与儿童社区获得性肺炎严重程度及免疫功能相关性研究

目的 分析不同严重程度肺炎的患儿25-羟维生素D₃[25-(OH)D₃]、体液免疫及细胞免疫水平,研究血清25-(OH)D₃水平与儿童社区获得性肺炎(CAP)严重程度及免疫功能的相关性。方法 收集2016年3月-2017年3月在首都儿科研究所附属儿童医院收治的175例CAP患儿作为病例组,根据病情严重程度分为重症肺炎组(n=87),轻症肺炎组(n=88)。同期采用随机数字法收集在本院保健科进行健康体检的100例健康儿童作为对照组。测定3组儿童的血清25-(OH)D₃水平,同时检测所有肺炎组患儿白细胞计数、中性粒细胞及淋巴细胞比例、血浆C反应蛋白(CRP)、降钙素原(PCT)、体液免疫(IgA、IgG、IgM),细胞免疫(CD4、CD8、CD19、CD16/56)水平,并分析血清25-(OH)D₃水平与炎性细胞及免疫功能之间的相关性。结果 重症肺炎组、轻症肺炎组和对照组血清25-(OH)D₃水平差异有统计学意义(F＝76.95,P<0.05),轻、重症肺炎组间白细胞计数、CRP、PCT、IgG比较差异有统计学意义(P均<0.05)。Pearson相关分析结果显示血清25-(OH)D₃水平与白细胞总数呈负相关(r=-0.307,P<0.05)。多因素Logistic回归分析显示,25-(OH)D₃和IgG水平是儿童重症社区获得性肺炎的高危因素。结论 血清25-(OH)D₃与IgG水平与儿童社区获得性肺炎病情严重程度关系密切,重症肺炎患儿血清25-(OH)D₃与IgG水平明显低于轻症肺炎组,检测患儿的血清25-(OH)D₃和IgG水平对于疾病的早期评估有重要的意义。