细胞因子与老年重症肺部感染病原菌的关系探讨

目的 探讨细胞因子与老年人重症肺部感染病原菌的关系。方法 对20例健康老年人、79例ICU感染早期、感染控制后的老年重症肺部感染患者空腹采血，酶联免疫吸附（ELISA）法测定样本的白细胞介素2受体（IL-2R）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、肿瘤坏死因子α（TNF-α）及C反应蛋白（CRP）的含量，并行冷凝集试验（CAT）排除支原体感染；同时细菌培养明确病原菌，评价细胞因子与老年重症肺部感染病原菌的关系。结果 血清IL-2R、IL-6、CRP水平革兰阴性菌（G^-）感染组、革兰阳性菌（G^-）感染组、真菌感染组分别为较对照组均明显增高（P〈0．01），差异有统计学意义；而感染组间比较差异无统计学意义（P〉0．05）。G^＋感染组的血清IL-8水平明显低于G^-感染组及真菌感染组（P〈0．01），但与对照组比较，差异无统计学意义（P〉0．05）。G^＋感染组血清TNF-α水平较对照组增高（P〈0．05），但不如G^-感染组、真菌感染组较对照组增高明显（P〈0．01）；G^＋感染组血清TNF-α水平与G^-感染组、真菌感染组比较显著低下（P〈0．05）。结论 老年重症肺部G^＋感染者血清IL-2R、IL-6、CRP显著升高，而TNF-α升高较轻，IL-8降低，G^-感染患者、真菌感染患者血清TNF-α、IL-2R、IL-6、IL-8、CRP均显著升高。老年肺部感染初期血清TNF-α、IL-8水平可以做为早期协助预测病原菌的指标。     

Comparative Studies of Superoxide Production by Microbial Wall Product-Primed Neutrophils in Ulcerative Colitis

A diminished tolerance to the normal gut bacterial flora has been suggested to be pathogenic in ulcerative colitis (UC) and the aim of this study was to evaluate the priming effect of selected bacterial wall products on UC neutrophil granulocytes. Neutrophils from 10 UC patients and 10 healthy controls were primed with bacterial lipoprotein (BLP) or lipopolysaccharide (LPS) and subsequently activated. Extracellular superoxide production was measured by the cytochrome c reduction assay. Priming neutrophils with BLP or LPS dose dependently increased the superoxide production in both UC and controls (P < 0.01), and BLP was more potent than LPS (P < 0.05). No differences were found between UC and controls. UC neutrophils do not seem to have an intrinsic abnormality with reduced tolerance to bacterial substances. However, bacterial wall products such as BLP modify neutrophil tissue-destruction mechanisms and might be pivotal for perpetuation of chronic colonic inflammation.     

老年肺结核患者继发下呼吸道感染98例病原菌谱和药敏分析

目的了解老年肺结核患者继发下呼吸道感染的病原菌谱及对常用药物的敏感情况。方法对1999年至2004年间住院的98例老年肺结核(老年组)和86例非老年肺结核(对照组)继发下呼吸道感染患者的痰菌培养及药敏结果作回顾性分析,比较两组病例的病原菌谱及对8种常用药物的敏感性情况。结果老年组和对照组,革兰氏阴性杆菌检出率分别为69.39%、52.33%,革兰氏阳性菌检出率分别为18.37%、36.05%,均为P<0.05。结论老年肺结核患者继发下呼吸道感染的病原菌以革兰氏阴性杆菌为主,其对常用抗菌药物的敏感性低。     

他汀类药物对社区获得细菌性肺炎预后影响的研究

目的 探讨他汀类药物是否降低社区获得细菌性肺炎住院患者的死亡风险.方法 通过回顾性队列研究的方法,收集40岁以上社区获得细菌性肺炎患者的资料,服用他汀类药物的肺炎患者定义为暴露组,同时期未服用过他汀类药物的肺炎患者为对照组,用非条件Logistic多元回归模型控制混杂因素后对两组结局进行比较,并分析相关实验室结果.结果 本研究收集了1 272个住院肺炎病例,其中暴露组172人(13.5％),对照组1 100人(86.5％).在Logistic回归模型中,经过年龄等调整后,他汀类药物对肺炎30 d病死率的风险值为0.512 (95％CI:0.195～1.350).而经过调整后他汀类药物对肺炎ICU入住率与机械通气使用率的风险值分别为0.793 (95％CI:0.404～1.558)、0.488(95％CI:0.202～1.181).结论 服用他汀类药物未能显著降低社区获得性肺炎患者住院30 d病死率与ICU入住率以及机械通气使用率.     

孟鲁司特钠咀嚼片细菌计数检查方法的比较与优化

目的:优化孟鲁司特钠咀嚼片细菌计数检查方法。方法:用两种稀释剂分别制备供试液,按2010年版《中国药典》进行回收率试验,比较不同计数方法回收率的高低,以选择该药品最佳的细菌计数方法。结果:添加0.5%大豆卵磷脂和4%聚山梨酯80的稀释剂可去除孟鲁司特钠咀嚼片的抗菌活性,细菌计数检查方法为常规法回收率可达70%以上;未添加中和剂组细菌计数检查方法为常规法回收率低于70%,需用1∶1 000稀释级常规法才能使回收率达到70%以上。结论:采用稀释剂中添加0.5%大豆卵磷脂和4%聚山梨酯80法可优化孟鲁司特钠咀嚼片的细菌计数检查方法。     

Conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis: a randomized clinical trial

Objective: Efficacy of the conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis was compared.

Methods: In a randomized clinical trial 44 patients with acute bacterial meningitis were randomly assigned to the conventional- or high-dose vancomycin groups. Clinical and laboratory parameters were used for evaluation of response to the treatment regimens.

Results: In the high-dose group, leukocytosis and fever resolved significantly faster than those in the conventional group. Furthermore, the length of hospitalization was shorter and Glasgow Coma Scale at the end of 10th day was significantly lower in the high dose compared to the conventional group. Trend of creatinine clearance changes did not differ significantly between the two groups.

Conclusion: In comparison to the conventional-dose regimen, the high-dose vancomycin regimen was associated with significantly more favorable clinical response without increase in the incidence of nephrotoxicity in patients with acute bacterial meningitis.     

Metronidazole for the treatment of vaginal infections

Introduction: Metronidazole, undoubtedly the most widely known and used member of the nitroimidazole drug class, remains not only first line therapy for bacterial vaginosis (BV) and trichomoniasis, but serves as drug of first choice. Available and used both orally and topically with high efficacy rates, especially for trichomoniasis, nevertheless numerous unanswered questions remain regarding mechanism of action. Given the extraordinary global frequency of vaginitis due to BV and trichomoniasis, especially the high recurrence rate observed in BV, it is timely to critically examine the therapeutic role of metronidazole in management decisions.

Areas covered: Search methodology used PUBMED literature review. In spite of many years of successful use, multiple questions exist regarding optimal dose and duration of therapy especially in the management of BV. Antimicrobial drug resistance remains uncommon in spite of extensive use. The use of metronidazole for vaginitis is reviewed in this article together with challenges to improving its more effective administration.

Expert opinion: Currently metronidazole or the family of nitroimidazoles, represent the drugs of first choice for trichomonas vaginitis and first line therapy for BV. Drug resistance for both entities remains uncommon; however, in contrast to trichomoniasis where relapse is rare, high recurrence rates are common in women with BV. Metronidazole appears to allow persistence of vaginal microbiome microorganisms which translate into frequent relapses. In the absence of new therapeutic alternatives, strategies are being developed to enhance drug cure rates.     

Oritavancin for acute bacterial skin and skin structure infections

Introduction: Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSIs) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapid bactericidal agent approved for the treatment of ABSSSIs. Its prolonged half-life with one-time intravenous (i.v.) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of i.v. therapy.

Areas covered: This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/pharmacokinetics and efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability.

Expert opinion: If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged i.v. therapy, it will be sought as an alternative antibiotic therapy for ABSSSIs. In addition, further clinical data demonstrating efficacy in Gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market.     

Treatment strategies for central nervous system infections: an update

Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.

Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.

Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.     

Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

BackgroundClinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice.AimTo evaluate the diagnostic value of published CPRs for febrile children in primary care.MethodAlarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. ‘Referral to emergency department (ED)’ was used as a proxy outcome measure for ‘serious infection’. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area).ResultsA total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0–4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were ‘ill appearance’, ‘inconsolable’, and ‘abnormal circulatory or respiratory signs’. The height of the CPR’s predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months.ConclusionPublished CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice.