The global epidemic of multidrug-resistant Salmonella Typhimurium DT104 provides an important example, both in terms of the agent and its resistance, of a widely disseminated zoonotic pathogen. Here, ...with an unprecedented national collection of isolates collected contemporaneously from humans and animals and including a sample of internationally derived isolates, we have used whole-genome sequencing to dissect the phylogenetic associations of the bacterium and its antimicrobial resistance genes through the course of an epidemic. Contrary to current tenets supporting a single homogeneous epidemic, we demonstrate that the bacterium and its resistance genes were largely maintained within animal and human populations separately and that there was limited transmission, in either direction. We also show considerable variation in the resistance profiles, in contrast to the largely stable bacterial core genome, which emphasizes the critical importance of integrated genotypic data sets in understanding the ecology of bacterial zoonoses and antimicrobial resistance.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Transcriptional profiling of Campylobacter jejuni during colonization of the chick cecum identified 59 genes that were differentially expressed in vivo compared with the genes in vitro. The data ...suggest that C. jejuni regulates electron transport and central metabolic pathways to alter its physiological state during establishment in the chick cecum.
Background: The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in ...immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy. Methods: A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed. Results: Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher’s exact test). Conclusions:P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.
We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic Salmonella infections.
We infected mice with isogenic ...molecularly tagged subpopulations of either a fast-growing WT or a slow-growing ΔaroC Salmonella strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin.
Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment.
In Salmonella infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.
Summary Objective To estimate the lifetime risk of undergoing primary total hip (THR) or knee (TKR) replacement in the UK. Method A Population-based cohort study of 25,845 patients who had undergone ...a THR and 23,260 patients who had undergone a TKR between 1991 and 2006, using data from the UK General Practice Research Database. Results The estimated mortality-adjusted lifetime risk of THR at age 50 for the year 2005 was 11.6% (95% CI: 11.1, 12.1) for women and 7.1% (95% CI: 6.7, 7.5) for men. For TKR the risks were 10.8% (95% CI: 10.3, 11.3) for women and 8.1% (95% CI: 7.6, 8.5) for men. Between 1991 and 2006, the lifetime risk of THR at age 50 rose from 4.0% (95% CI: 3.5, 4.4) to 11.1% (95% CI: 10.6, 11.6) for women and for men from 2.2% (95% CI: 1.8, 2.5) to 6.6% (95% CI: 6.2, 7.0). Over the same period, for TKR the risk for women increased from 2.9% (95% CI: 2.6, 3.3) to 10.6% (95% CI: 10.1, 11.1) and for men from 1.8% (95% CI: 1.5, 2.2) to 7.7% (95% CI: 7.3, 8.2). Conclusion The lifetime risk of undergoing THR or TKR is estimated to be substantially less than the risk of developing symptomatic hip or knee osteoarthritis. For the knee, the difference between these risk estimates is particularly wide. The reasons for the size of these differences are not clear, and further work is needed to quantify the extent of latent demand for these cost-effective and established interventions among the population with symptomatic osteoarthritis of the hip or knee.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
The severity of infections caused by Salmonella enterica serovar Typhimurium varies depending on the host species. Numerous virulence genes have been identified in S. Typhimurium, largely ...from studies in mice, but their roles in infections of other species remain unclear. In the most comprehensive survey of its kind, through the use of signature‐tagged mutagenesis of S. Typhimurium we have identified mutants that were unable to colonize calf intestines, mutants unable to colonize chick intestines and mutants unable to colonize both species. The type three secretion systems encoded on Salmonella pathogenicity islands (SPIs) 1 and 2 were required for efficient colonization of cattle. However, disruption of these secretion systems only caused a minor defect in S. Typhimurium colonization of chicks. Transposon insertions in SPI‐4 compromised S. Typhimurium colonization of cattle, but not chicks. This is the first data confirming a role for SPI‐4 in pathogenesis. We have also been able to ascribe a role in colonization for cell surface polysaccharides, cell envelope proteins, and many ‘housekeeping’ genes and genes of unknown function. We conclude that S. Typhimurium uses different strategies to colonize calves and chicks. This has major implications for vaccine design.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted ...in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC).
A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations.
Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.
In this randomized trial involving 454 patients with pleural infections that required antibiotic therapy and chest-tube drainage, there was no benefit from the use of intrapleural streptokinase in ...terms of survival, the need for surgery, the length of the hospital stay, or the resolution of radiographic abnormalities.
In this trial involving 454 patients with pleural infections, there was no benefit from the use of intrapleural streptokinase in terms of survival, the need for surgery, the length of the hospital stay, or the resolution of radiographic abnormalities.
Pleural infection develops in about 65,000 patients each year in the United States and the United Kingdom.
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Approximately 15 percent of patients die,
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which is similar to the death rate among patients hospitalized with pneumonia,
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,
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and 15 to 40 percent require surgical drainage of the infected pleural space.
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,
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The median duration of inpatient care is 15 days, with 20 percent of patients remaining in the hospital for a month or longer.
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Apart from antibiotic therapy, treatment in patients with pleural infection consists mainly of drainage of the infected pleural fluid, and the intrapleural administration of fibrinolytic drugs is . . .
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