Oropharyngeal decontamination in intensive care patients: less is not more

Ventilator-associated pneumonia (VAP) is a common cause of morbidity, antibiotic use, increased length of stay and, possibly, increased mortality in ICU patients. Colonization of the oropharyngeal cavity with potentially pathogenic micro-organisms is instrumental in the pathogenesis of VAP, and selective oropharyngeal decontamination (SOD) with antibiotics (AB-SOD) or antiseptics, such as chlorhexidine gluconate (CHX-SOD), has been associated with reduced incidences of VAP. In a recent issue of Critical Care Scannapieco and colleagues investigated differences in oropharyngeal colonization between mechanically ventilated patients receiving oropharyngeal decontamination with 0.12% CHX-SOD either once or twice daily compared to placebo. CHX-SOD was associated with a reduction in Staphylococcus aureus colonization, but the study was underpowered to demonstrate a reduction in VAP incidence. We urgently need well-designed and adequately powered studies to evaluate the potential benefits of CHX-SOD on patient outcome in ICUs

Why sensitive bacteria are resistant to hospital infection control.

Background: Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. Methods: We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio ( IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. Results: For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤  0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while communityacquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Conclusions: Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally, following differences in their adaptation to hospital and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains

Within-Host Evolution of the Dutch High-Prevalent<i> Pseudomonas aeruginosa</i> Clone ST406 during Chronic Colonization of a Patient with Cystic Fibrosis

This study investigates adaptation of ST406, a prevalent P. aeruginosa clone, present in 15% of chronically infected cystic fibrosis (CF) patients in the Netherlands, in a newly infected CF patient during three years using whole genome sequencing (WGS), transcriptomics, and phenotypic assays, including biofilm formation. WGS-based phylogeny demonstrates that ST406 is genetically distinct from other reported CF related strains or epidemic clones. Comparative genomic analysis of the early (S1) and late (S2) isolate yielded 42 single nucleotide polymorphisms (SNPs) and 10 indels and a single 7 kb genomic fragment only found in S2. Most SNPs and differentially expressed genes encoded proteins involved in metabolism, secretion and signal transduction or transcription. SNPs were identified in regulator genes mexT and exsA and coincided with differential gene expression of mexE and mexF, encoding the MexE/F efflux pump, genes encoding the type six secretion system (T6SS) and type three secretion system (T3SS), which have also been previously implicated in adaptation of other P. aeruginosa strains during chronic infection of CF lungs. The observation that genetically different strains from different patients have accumulated similar genetic adaptations supports the concept of adaptive parallel evolution of P. aeruginosa in chronically infected CF patients. Phenotypically, there was loss of biofilm maturation coinciding with a significant lower level of transcription of both bfmR and bfmS during chronic colonization. These data suggest that the high-prevalent Dutch CF clone ST406 displays adaptation to the CF lung niche, which involves a limited number of mutations affecting regulators controlling biofilm formation and secretion and genes involved in metabolism. These genes could provide good targets for anti-pseudomonal therapy

New methods to analyse microarray data that partially lack a reference signal

BACKGROUND: Microarray-based Comparative Genomic Hybridisation (CGH) has been used to assess genetic variability between bacterial strains. Crucial for interpretation of microarray data is the availability of a reference to compare signal intensities to reliably determine presence or divergence each DNA fragment. However, the production of a good reference becomes unfeasible when microarrays are based on pan-genomes.When only a single strain is used as a reference for a multistrain array, the accessory gene pool will be partially represented by reference DNA, although these genes represent the genomic repertoire that can explain differences in virulence, pathogenicity or transmissibility between strains. The lack of a reference makes interpretation of the data for these genes difficult and, if the test signal is low, they are often deleted from the analysis. We aimed to develop novel methods to determine the presence or divergence of genes in a Staphylococcus aureus multistrain PCR product microarray-based CGH approach for which reference DNA was not available for some probes. RESULTS: In this study we have developed 6 new methods to predict divergence and presence of all genes spotted on a multistrain Staphylococcus aureus DNA microarray, published previously, including those gene spots that lack reference signals. When considering specificity and PPV (i.e. the false-positive rate) as the most important criteria for evaluating these methods, the method that defined gene presence based on a signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics. For this method specificity was 100% and 82% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively, and PPV were 100% and 76% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively. CONCLUSION: A definition of gene presence based on signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics, allowing the analysis of 6-17% more of the genes not present in the reference strain. This method is recommended to analyse microarray data that partially lack a reference signal

Тарикъатлар хусусиетлери

В статье проанализированы в историко-хронологическом и диахроническом аспектах весьма важный социальный институт – суфийские братства и их деятельность. Работа посвящена по преимуществу особенностям и характерным чертам практического (прагматического, или рефлекторного) суфизма, который функционально осуществляется через братства, а не специфике суфизма интеллектуального, то есть не его религиозно-философским и этико-моральным доктринам и положениям

Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

INTRODUCTION: Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD. METHODS: We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use. RESULTS: Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups. CONCLUSIONS: Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol

Внутригодовые (сезонные) изменения общего содержания биогенных элементов и кислорода в различных районах Севастопольской бухты

Для каждого месяца в период май 1998 г. – май 1999 г. рассчитано абсолютное содержание биогенных элементов и кислорода в пяти различных районах Севастопольской бухты и для всей бухты в целом. Показано, что наиболее чистый (возле входа в бухту) и наиболее грязный (Южная бухта) районы отличаются по динамике накопления и расходования биогенных элементов. Максимальный запас неорганических форм азота, фосфора, и кремнекислоты во всех районах Севастопольской бухты, за исключением района Инкерманской бухты, приходится на январь.Total content of biogenic elements and oxygen in five different areas of the Sevastopol Bay and for the whole bay in general is estimated for each month starting from May, 1998 up to May, 1999. It is shown that the purest (near the bay entrance) and the dirtiest (the Southern Bay) areas are distinguished for dynamics of biogenic elements accumulation and expense. Maximum storage of inorganic forms of nitrogen, phosphorus and silicic acid in all the areas of the Sevastopol Bay, excepting the Inkerman Bay area, falls on January

Adequacy of Antimicrobial Treatment and Outcome of Staphylococcus aureus Bacteremia in 9 Western European Countries

Background.Little is known about the incidence of inadequate treatment of severe Staphylococcus aureus infection in Europe. We aimed to evaluate the adequacy of antibiotic therapy for S. aureus bacteremia (SAB), to identify determinants of inadequate treatment, and to determine the effect of inadequate treatment on patient outcome in a representative selection of hospitals in 9 Western European countries. Methods.In this retrospective cohort study, all adult patients with SAB (due to methicillin-susceptible S. aureus [MSSA] or methicillin-resistant S. aureus [MRSA]) who were admitted to 60 randomly selected hospitals from 1 November 2007 through 31 December 2007 were included. Adequate antimicrobial therapy was defined as intravenous administration of at least 1 antibiotic to which the isolate showed in vitro susceptibility that was initiated within 2 days after onset of SAB. Results.A total of 334 SAB episodes (257 due to MSSA and 77 due to MRSA) were included. Ninety-four patients (28%) received inadequate empirical therapy (21% in the MSSA group and 52% in the MRSA group). Both length of stay before SAB onset and methicillin-resistant infection were associated with inadequate therapy, with adjusted odds ratios (ORs) of 1.01 (95% confidence interval [CI], 1.00-1.03) and 3.7 (95% CI, 2.2-6.4), respectively. Age (OR, 1.06; 95% CI, 1.03-1.10), Charlson comorbidity score (OR, 2.1; 95% CI, 1.2-3.6), severe sepsis or septic shock (OR, 2.7; 95% CI, 1.5-4.8), and intensive care unit stay at onset of SAB (OR, 2.9; 95% CI, 1.5-5.6) but not inadequate treatment (OR, 0.7; 95% CI, 0.4-1.3) were associated with increased 30-day mortality. Conclusion.Inadequate empirical antimicrobial therapy for SAB is common in Western Europe and is strongly associated with infection caused by MRSA. In this study, inadequate treatment was not associated with increased 30-day mortality rate