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1.
Cao J Chen T Li D Wong CK Chen D Xu W Zhang X Lam CW Yin Y 《Microbes and infection / Institut Pasteur》2008,10(14-15):1536-1542
Caseinolytic protease (ClpP) has been found to be highly conserved among different strains of Streptococcus pneumoniae and intraperitoneal immunization with ClpP could elicit protection against invasive pneumococcal infections. In this study, mucosal immunization with ClpP antigen induced both systemic and mucosal antibodies, and in this way reduced lung colonization in an invasive pneumococcal pneumonia model and also protected mice against death in an intraperitoneal-sepsis model. Surface localization of ClpP was confirmed using flow cytometry analysis. Furthermore, characterization of human sera for anti-ClpP IgG antibody levels demonstrated that ClpP protein was immunogenic in healthy children and was expressed during disease based on the elevated antibody levels in infected individuals. Finally, we describe that in vitro functional anti-ClpP antibody could kill streptococcus pneumoniae by polymorphonuclear leukocytes in a complement-dependent assay. To our knowledge, this is the first study about the protective efficacy of mucosal immunization with ClpP as a promising pneumococcal protein antigen. 相似文献
2.
Standardization of acellular pertussis vaccines. 总被引:1,自引:0,他引:1
J G Kreeftenberg 《Biologicals》1999,27(2):115-117
In comparison with the current whole cell pertussis vaccine, the new generation of acellular pertussis vaccines opens new opportunities to improve the standardization of the product, because well defined and characterized components are used in these new products.However, different compositions, purification and inactivation methods are used by different manufacturers. Consequently the various acellular pertussis vaccines in the world are difficult to compare in a meaningful manner using simple laboratory tests. In addition, the absence of a reliable animal model and serological correlates with protection in children are other complicating factors.For that reason it seems that the consistency in manufacturing based on a clinically validated production process is the best way to ensure the safety and efficacy of routinely produced acellular pertussis vaccines.Laboratory tests to monitor the antigen content, purity, safety and immunogenicity seem to be the best approach to standardize this new generation of pertussis vaccines against homologous standard vaccines with known clinical efficacy and safety and to support the consistency in manufacture. 相似文献
3.
The second-generation triazoles, voriconazole and posaconazole, have found important roles in the management of invasive fungal
infections in high-risk patients. Both agents are more active against Candida albicans and the non-albicans Candida species than the first-generation triazoles. They are active against Aspergillus species, including those species less susceptible to polyenes, and against a variety of non-Aspergillus molds. In contrast to posaconazole, voriconazole has no activity against the zygomycetes, and breakthrough infections have
been observed. Both are well absorbed, but considerable intra- and interpatient pharmacokinetic variability has raised the
question of therapeutic drug monitoring. Both inhibit hepatic cytochrome P450 isoenzymes, which are important in the metabolism
of various drugs coadministered in the management of high-risk patients. Clinical trials have demonstrated the safety and
efficacy of both agents for antifungal prophylaxis and treatment in invasive candidiasis, invasive aspergillosis, and in invasive
fungal infections caused by a variety of non-Aspergillus molds. Posaconazole is the only triazole approved for use in the treatment of invasive zygomycosis. Voriconazole is the accepted
standard first-line therapy for invasive aspergillosis. 相似文献
4.
Luis Madero-López 《Revista iberoamericana de micología》2009,26(1):62-64
Micafungin is one of three echinocandins, a novel class of antifungal agents active against 1,3-β-D glucan in the fungal cell wall. It is a favorable safety profile have made it an attractive option in the treatment of invasive Candida and Aspergillus infections. Available studies have shown that younger children have lower Cmax, shorter t½ and faster clearance than adults. 相似文献
5.
Development of invasive fungal infection is the result of the complex interaction between fungal and host factors. The outcome
of infection, once it has developed, depends upon appropriate use of antifungal therapy, surgical debridement as indicated,
and improvement of host defenses. Thus, there have been major efforts for development of new strategies for immunomodulation
and augmentation of host defenses in prevention and treatment of invasive mycoses. These modalities include granulocyte and
granulocyte-macrophage colony-stimulating factors, interferon-γ, granulocyte transfusions, immunotherapy with infusion of
dendritic cells and T cells, anti-heat shock protein 90 monoclonal antibodies, long pentraxin 3, mannose-binding lectin, and
deferasirox. Although major strides in our understanding of augmentation of host response to invasive fungal infections are
opening up novel avenues of therapy to harness patients’ innate immune systems against these frequently lethal pathogens,
well-designed clinical trials are needed to demonstrate safety and efficacy of these new approaches. 相似文献
6.
BackgroundIn neonatal intensive care units, deep fungal disease due to Candida spp. are an important clinical problem, partly due to the increasing prevalence of Candida disease and also to the high associated and constant morbimortality; both factors are independently maintained though there has been a significant improvement in the management of neonatal patients.AimsTo define the therapeutic use of micafungin for the treatment of neonatal invasive candidiasis.MethodsWe use a review of biomedic data bases namely Medline and EMBASE.ConclusionsMicafungin is the latest introduced echinocandin. It has a wide spectrum of activity and covers Candida albicans and non-albicans Candida species. It has scarce drugs interactions and is devoid of toxicity, being an attractive approach for the treatment of invasive candidiasis (without meningitis, endocarditis and endophthalmitis). Althought the European Medicines Agency approved in 2008 the use of Micafungin for the treatment of invasive candidiasis in children, the available clinical experience is limited and currently more clinical studies are warranted to define its efficacy and safety in neonates. 相似文献
7.
8.
Jean T. Coulibaly Yve K. N'Gbesso Stefanie Knopp Jennifer Keiser Eli��zer K. N'Goran J��rg Utzinger 《PLoS neglected tropical diseases》2012,6(12)
Background
In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied.Methodology
We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d''Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians.Principal Findings
Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children.Conclusions/Significance
Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d''Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth.Trial Registration
Controlled-Trials.com ISRCTN53172722 相似文献9.
Jason C. Gallagher 《Current fungal infection reports》2009,3(2):69-76
Studies of pharmacodynamics are used to develop dosing regimens that maximize safety and efficacy in clinical practice. Antifungal
pharmacodynamics is a growing field, and studies are increasingly moving from the in vitro phase to animal models to clinical
evaluations. Preclinical studies that determine pharmacodynamic predictors of efficacy and safety provide valuable data in
the determination of a dosage regimen, but evaluations of antifungal pharmacodynamic parameters in vivo are less common. This
article reviews areas where antifungal pharmacodynamics has been evaluated in clinical trials to develop principles that may
be used in the pharmacotherapy of invasive mycoses. 相似文献
10.
Pramodini B. Kale-Pradhan Sheila M. Wilhelm Leonard B. Johnson 《Current fungal infection reports》2012,6(2):107-112
Invasive infections due to Candida species are a major cause of healthcare-associated infections and are associated with a high mortality rate. Candida parapsilosis (C. parapsilosis) is associated with higher minimum inhibitory concentrations (MICs) of echinocandins creating controversy concerning their role in therapy for invasive disease. Despite the higher MICs observed in vitro, clinical resistance is rare and clinical success may occur with higher MICs against this species. A large number of non-comparative studies have demonstrated echinocandins efficacy against C. parapsilosis in invasive candidiasis and candidemia. In addition, pooled data from prospective studies have demonstrated in a meta-analysis that echinocandins are non-inferior to comparator anti-fungal drugs in the treatment of C. parapsilosis. Adverse events reported in the trials were similar in both echinocandin and comparator groups. Based on available data from randomized and non-randomized trials, echinocandins appear to be effective alternative agents for the treatment of invasive C. parapsilosis infections. 相似文献
11.
Two new vaccines have recently been shown to be safe and effective in protecting young children against severe rotavirus gastroenteritis. Although both vaccines are now marketed worldwide, it is likely that improvements to these vaccines and/or the development of future generations of rotavirus vaccines will be desirable. This Review addresses recent advances in our knowledge of rotavirus, the host immune response to rotavirus infection and the efficacy and safety of the new vaccines that will be helpful for improving the existing rotavirus vaccines, or developing new rotavirus vaccines in the future. 相似文献
12.
Sarah M. Wieczorkiewicz Jacqueline Jourjy Larry Danziger 《Current fungal infection reports》2009,3(2):103-110
The incidence and severity of invasive fungal infections are on the rise and they pose a risk of significant morbidity and
mortality. The cost burden of fungal infections in the United States is high. There are many newer, less toxic antifungal
agents to manage these challenging infections; however, these agents also carry a high cost of their own. When considering
an antifungal agent for a specific patient, it is important to consider safety, efficacy, and cost, thus making it essential
to continually evaluate the antifungal pharmacoeconomic literature to assist in the therapeutic decision-making process for
patients with invasive fungal infections. Unfortunately, there is a lack of pharmacoeconomic studies addressing the costs
associated with the treatment and prevention of fungal infections. Future large-scale clinical studies should include pharmacoeconomic
analyses and end points that encompass all costs associated with antifungal drug use, not solely drug acquisition costs. 相似文献
13.
杨丽 《中国微生态学杂志》2010,22(1):67-68
目的评价米卡芬净治疗重症侵袭性真菌感染患者的疗效和安全性。方法采用回顾性分析2007年12月~2009年6月大连医科大学附属二院ICU病房40例侵袭性真菌感染患者应用米卡芬净治疗的临床资料。结果40例患者中,痊愈10例(25%),显效18例(45%),总有效率为70%,真菌清除率为60.8%,不良反应少,所有患者均耐受治疗。结论米卡芬净治疗重症侵袭性真菌感染安全、有效。 相似文献
14.
Montejo González JC Catalán González M León Gil C 《Revista iberoamericana de micología》2008,25(2):107-118
Anidulafungin is a new echinocandin that appears to have several advantages over existing antifungals. It is unique because it slowly degrades in humans, undergoing a process of biotransformation rather than being metabolized. It exhibits high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In several clinical studies investigating Candida esophagitis; candidemia and invasive candidiasis, the clinical efficacy of this echinocandin was similar, or even superior, to that of established antifungals in candidemia. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that anidulafungin can be used as salvage therapy in life-threatening fungal infections. The limited toxicity profile, minimal drug-drug interactions and the fact that does not require dosage adjustment in subjects with hepatic or renal impairment, establishes this echinocandin as an attractive new option for the treatment of invasive fungal infections. 相似文献
15.
There exists an abundance of literature on the prospects for developing vaccines against the etiologic viral agent of acquired immunodeficiency syndrome (AIDS). Excellent reviews from a variety of investigators are available on this subject. It is our intention to review the literature relative to potential strategies for developing a successful AIDS vaccine and to impart some of our concerns on the different types of vaccine that are being tested. We have also focused on some vaccine strategies that have not received much attention in previous review articles. Finally, the role of animal models in assessing vaccine safety and efficacy against AIDS has been briefly described. 相似文献
16.
Pre-release monitoring of Alliaria petiolata (garlic mustard) invasions and the impacts of extant natural enemies in southern Michigan forests 总被引:1,自引:0,他引:1
Monitoring of populations of a target weed species prior to releasing natural enemies has the potential to improve the rigor and safety of biological control and to determine the invader’s impacts on native communities while creating a reference point for evaluating the efficacy of subsequent biocontrol agent releases. Eight populations of garlic mustard, Alliaria petiolata (M. Bieb) Cavara and Grande (Brassicaceae), an invasive weed in southern Michigan, were monitored in anticipation of releases of classical biological control agents. The A. petiolata populations were shown to be expanding with 44.4% of initially uninvaded sampling quadrats becoming invaded after four years. While 88.2% of quadrats with A. petiolata showed evidence of foliar damage from pathogens and browsing by mammals, insects and other invertebrates, levels of damage were low and had little impact on rosette or seedling survival. Contrary to expectations, damage was positively correlated with A. petiolata fecundity (P = 0.0465). Given the continued expansion of A. petiolata and the lack of significant herbivore damage by acquired natural enemies, a biological control program should be considered against this invasive plant. If biological control agents are released, the results of this study will provide a benchmark for evaluating their performance. 相似文献
17.
泊沙康唑为新一代三唑类广谱抗真菌药,临床主要用于侵袭性曲霉菌病、念珠菌病的预防和难治性口咽念珠菌病的治疗,具有抗菌
活性高、耐受性好、不良反应少等特点,但其口服后生物利用度具有较大的个体差异。综述泊沙康唑混悬液的药动学影响因素、不同患者
人群的药动学特征以及群体药动学特征、药动学 / 药效学特性、治疗药物监测对临床疗效和不良反应的重要影响,以指导临床个体化用药,
提高用药的有效性和安全性。 相似文献
18.
The coming of age of niche vaccines?: Effect of vaccines on resistance profiles in Streptococcus pneumoniae 总被引:1,自引:0,他引:1
McGee L 《Current opinion in microbiology》2007,10(5):473-478
Pneumococcal conjugate vaccine is not only effective against invasive and non-invasive disease in all ages but also has a significant impact on antibiotic-resistant infections since a number of resistant serotypes are targeted by the vaccine. Surveillance studies in the post-licensure years have shown an increase in non-vaccine types both in carriage and disease isolates. There appears to be an increasing trend in antimicrobial resistance among these non-vaccine types, especially in serotype 19A. The impact these non-vaccine types will have on disease remains to be seen, but clearly continued efforts at characterizing the pneumococcal population are essential for future surveillance. Although expanded vaccine formulations with efficacy against a wider range of serotypes will be useful, reduction of drug-resistant Streptococcus pneumoniae will require a combination of the conjugate vaccine and a reduction in antimicrobial use. 相似文献
19.
Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease in infants, young children, immunocompromised individuals, and the elderly. However, despite ongoing efforts to develop an RSV vaccine, there is still no authorized RSV vaccine for humans. Baculovirus has attracted attention as a vaccine vector because of its ability to induce a high level of humoral and cellular immunity, low cytotoxicity against various antigens, and biological safety for humans. In this study, we constructed a recombinant baculovirus- based vaccine expressing the M2 protein of RSV under the control of cytomegalovirus promoter (Bac_RSVM2) to induce CD8+ T-cell responses which play an important role in viral clearance, and investigated its protective efficacy against RSV infection. Immunization with Bac_RSVM2 via intranasal or intramuscular route effectively elicited the specific CD8+ T-cell responses. Most notably, immunization with Bac_RSVM2 vaccine almost completely protected mice from RSV challenge without vaccine-enhanced immunopathology. In conclusion, these results suggest that Bac_RSVM2 vaccine employing the baculovirus delivery platform has promising potential to be developed as a safe and novel RSV vaccine that provides protection against RSV infection. 相似文献
20.
Immune responses against non-vaccine biologics can affect their efficacy and safety, resulting in adverse events that could include administration reactions, hypersensitivity, deficiency syndromes and lack of a clinical response in treated patients. With the relatively recent development of numerous biologics, immunogenicity testing has become a key component in the demonstration of clinical safety and efficacy; in fact, it is highly unlikely that regulatory approval would be granted for a biologic without an assessment of its immunogenicity. However, recommendations from regulatory agencies regarding the requirements for when and how to carry out immunogenicity testing are dispersed among numerous guidance documents. To enable the evaluation of the effects of immunogenicity on safety and efficacy, the authors have consolidated recommendations from the regulatory guidelines, and present current approaches and future directions for the assessment of immunogenicity. 相似文献