GMS infectious diseases最新文献

Influenza is a serious and frequently underestimated, but vaccine preventable disease. The adamantane derivates rimantadine and amantadine and the neuraminidase inhibitors zanamivir and oseltamivir are the only antiviral drugs currently approved in Europe for therapy and prophylaxis of influenza infections. Resistance to these drugs occurs due to mutations within the therapeutic target proteins M2 ion channel protein and viral neuraminidase. An unexpected occurrence of oseltamivir-resistant seasonal A(H1N1) viruses was detected in winter 2007/2008. The prevalence of these viruses increased rapidly and nearby all viruses circulating during the following seasons were resistant to oseltamivir. The A(H1N1)pdm09 viruses replaced the former seasonal A(H1N1) subtype during the 2009-2010 influenza season. Fortunately, resistance to neuraminidase inhibitors was detected in A(H1N1)pdm09, A(H3N2) and influenza B viruses only sporadically and was treatment related mostly. Comprehensive analyses of circulating viruses showed a high prevalence of A(H3N2) influenza viruses that are resistant to adamantane derivates since 2004/2005 and a progressive trend in the prevalence of resistant viruses up to 100% in following seasons. The M2 ion channel protein of A(H1N1)pdm09 viruses is associated with the Eurasian avian-like swine lineage and thus show "natural" resistance to adamantane derivates. Therefore, only neuraminidase inhibitors are recommended for influenza treatment today. This manuscript summarizes the occurrence and spread of antiviral resistant influenza viruses and highlights the importance for developing and/or approving new antiviral compounds.

The mean (SD) unbound fraction of moxifloxacin in plasma from patients with severe sepsis or septic shock was determined by ultrafiltration to 85.5±3.0% (range 81.9 and 91.6%) indicating a decreased protein binding of moxifloxacin in this population compared with the value of 58-60% provided in the Summary of Product Characteristics. However, previous investigations neglected the influence of pH and temperature on the protein binding of moxifloxacin. Maintaining physiological conditions (pH 7.4, 37°C) - as in the present study - the unbound fraction of moxifloxacin in plasma from healthy volunteers was 84%. In contrast, the unbound fraction of moxifloxacin was 77% at 4°C and 66-68% in unbuffered plasma or at pH 8.5 in fair agreement with previously published data. PK/PD parameters e.g. fAUC/MIC or ratios between interstitial fluid and free plasma concentrations, which were obtained assuming a protein binding rate of moxifloxacin of 40% or more, should be revised.

Objectives: To supplement the data collected in randomized clinical trials, the present study in patients with methicillin resistant Staphylococcus aureus (MRSA) pneumonia was conducted to explore the clinical effectiveness of linezolid and vancomycin in a routine clinical setting. Further, the overall costs of the patients' stay in the intensive care unit (ICU) were compared. Methods: This was a retrospective analysis of medical and reimbursement data of adult patients who were treated for MRSA pneumonia with linezolid or vancomycin. Since the subjects were not randomly assigned to treatments, propensity score adjustment was applied to reduce a potential selection bias. Results: In total, 226 patients were included; 95 received linezolid and 131 received vancomycin as initial therapy for MRSA pneumonia. Switches to another antibiotic were observed in 4 patients (4.2%) receiving linezolid and in 23 patients (17.6%) receiving vancomycin (logistic regression analysis; odds ratio linezolid/vancomycin: 0.183; 95% confidence interval [CI]: 0.052-0.647; p<0.01). All-cause in-hospital mortality was also lower in patients receiving linezolid (22 patients [23.2%] vs. 54 patients [41.2%]) (logistic regression analysis; odds ratio linezolid/vancomycin: 0.351; 95% CI: 0.184-0.671; p<0.01). The analysis of the total costs of stay in ICU did not reveal any major differences between the two treatment groups (cost ratio linezolid/vancomycin: 1.29; 95% CI: 0.84-1.98; p=0.24). Conclusions: These findings confirm in a routine clinical setting that linezolid is a valuable therapeutic alternative to vancomycin for the treatment of MRSA pneumonia. However, prospective studies in real-life patient populations are warranted.

Alveolar echinococcosis (AE) is the most Iethal human helminthic infection. The malignancy-like disease is rare, but morbidity and treatment costs are high. Objective of the study was to identify factors at baseline and during specific AE therapy influencing the long-term outcome of the disease. All patients with AE seen at the specialized treatment unit in Ulm between January 1992 and December 2011 were included in the analysis. The data of 312 patients were analyzed; 108 were diagnosed before 2000 (series A), 204 since 2000 (series B); 290 received specific AE treatment. Patients of series B were more often symptom-free at diagnosis (44.1% vs. 21.3%), had lower disease stages (50.0% vs. 34.2%) and more complete resections (57.7% vs. 20.0%), but higher rates of side effects and drug toxicity (54.1% vs. 40.8%). In series B, more patients remained relapse- or progression-free after 5 years (90.5% vs. 82.8%); after 10 years, the ratio of relapses converged (70.3% vs. 66.9%, p=0.0507). Relapses or progression occurred more often after incomplete surgery or long treatment pauses. The 5-year and 10-year survival rates were 96.9% and 90.6%, respectively, and 17% of the patients were cured. We observed a shift towards early diagnosis, earlier initiation of specific therapy and more complete resections after 2000. Although diagnosis and treatment of AE pose a challenge, with an individual interdisciplinary management 88.8% of the patients have a favorable outcome.

Zincophorin is a polyketide antibiotic that possesses potent activity against Gram-positive bacteria, including human pathogens. While a number of total syntheses of this highly functionalized natural product were reported since its initial discovery, the genetic basis for the biosynthesis of zincophorin has remained unclear. In this study, the co-linearity inherent to polyketide pathways was used to identify the zincophorin biosynthesis gene cluster in the genome of the natural producer Streptomyces griseus HKI 0741. Interestingly, the same locus is fully conserved in the streptomycin-producing actinomycete S. griseus IFO 13350, suggesting that the latter bacterium is also capable of zincophorin biosynthesis. Biological profiling of zincophorin revealed a dose-dependent inhibition of the Gram-positive bacterium Streptococcus pneumoniae. The antibacterial effect, however, is accompanied by cytotoxicity. Antibiotic and cytotoxic activities were completely abolished upon esterification of the carboxylic acid group in zincophorin.

Given the rapidly changing landscape of antimicrobial resistance, continuous monitoring of antimicrobial susceptibility in clinically relevant bacterial isolates plays an important role in the management of infectious diseases. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing worldwide surveillance programme monitoring the in vitro activity of tigecycline and a panel of representative comparator antibiotics. We report longitudinal susceptibility data on a large set of isolates (n=36,044) from clinically significant bacterial species collected in 25 microbiological laboratories from 2006 to 2014. Trends include a strong increase of carbapenem and levofloxacin resistance in Acinetobacter spp., and smaller increasing rates of ESBL-producing Escherichia coli and vancomycin-resistant enterococci. Across the reporting period, the tigecycline minimum inhibitory concentrations (MICs) at which 50% and 90% of isolates were inhibited remained stable and susceptibility rates were consistently high (93-100%) for all bacterial species.

Sepsis and meningitis are life threatening medical conditions. Culture-based methods are used for identification of the causative pathogens, but they can be improved by implementation of additional test systems. We evaluated the performance of the novel FilmArray blood culture identification (BCID; Biofire Diagnostics) panel for rapid and accurate identification of microorganisms in positive blood cultures and additionally, in this cerebrospinal fluid (CSF) pilot study for direct testing of CSF. A total of 107 positive blood cultures and 20 CSF samples (positive and negative) were investigated and compared to the routine procedures. Of the 107 positive blood cultures, 90.7% (97/107) showed monomicrobial growth and 9.3% (10/107) polymicrobial growth. The FilmArray BCID panel covered 89.3% (25/28) of the bacteria and 100% (2/2) of the yeasts found in this study and accurately identified all of them. From the 20 retrospective analyzed CSF, in 9 positive specimens 6 different bacterial species were identified. Discrepant identification results were found in 25% (5/20) and a low sensitivity of 50% (95% CI of 15.7% to 84.3%) was detected. Our study confirms the FilmArray BCID panel as a rapid, easy to handle PCR system with a good performance in positive blood cultures without Gram-staining result. However, our results additionally suggest that the system is not useful for direct CSF testing due to poor sensitivity.

Persistent infections with the hepatitis C virus (HCV) pose a profound global public health burden. In the past 5 years treatment of chronic hepatitis C has dramatically changed. Novel direct-acting antivirals (DAAs) specifically inhibiting viral enzymes or factors that are essential for the viral replication cycle have been developed and licensed for hepatitis C therapy. These novel drugs target the viral NS3/4A protease, the NS5B RNA-dependent RNA-polymerase or the replication factor NS5A. Combinations of DAAs against these targets are highly efficacious achieving virus elimination in the majority of treated patients. In countries where affordable, this rapid clinical development virtually replaced earlier interferon (IFN)-α based therapy that had been in use as standard of care for the last 25 years. With the approval of DAAs for the treatment of chronic hepatitis C the question emerged whether resistance-associated substitutions (RASs) might be of clinical relevance. Here, we discuss the available evidence for the possible benefit of resistance genotyping prior to therapy to optimize treatment of chronic hepatitis C.

Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR) and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively (p 0.642; p 0.773; p 0.087). In contrast, a slight decrease of IL-6 (p 0.599) was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP (p 0.028) and PCT (p 0.008) and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (p<0.001), while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP (p 0.005) and PCT (p 0.005) was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.

Mycotoxins are produced pre harvest by some molds and secreted into various food items of plant origin, such cereals, vegetables, spices, coffee and nuts. If the food items are not stored under adequate conditions, a post harvest contamination may also occur. Animals and humans take them up by food items and some of them are stored and accumulated in different tissues and organs, so that food of animal origin may be contaminated, too. Especially aflatoxin and ochratoxin are secreted into milk by consumers of contaminated food. Since milk represents the major food source of newborns and infants, they are notably exposed to these mycotoxins. This health risk for these individuals may be of particular importance, because their ability to metabolize these fungal toxic agents is not yet fully developed at this stage.