Epidemiology of Clostridium difficile -associated disease at University Hospital Basel including molecular characterisation of the isolates 2006-2007

A prospective study was conducted during a one-year period between 2006 and 2007 to describe the epidemiology of Clostridium difficile-associated disease (CDAD) at University Hospital Basel, Switzerland (UHBS) and to determine phenotypic and genotypic features of C. difficile strains isolated at the Microbiology Laboratory UHBS including strains from regional non-university hospitals. We prospectively identified 78CDAD cases at UHBS with an incidence of 2.65/1,000 hospitalised patients or 2.3/10,000 patient-days. Sixteen patients (20.5%) were infected with clindamycin-resistant strains of PCR-ribotype 027 during an outbreak at the geriatric hospital. Among 124 single-patient isolates, 28 (22.6%) were resistant to moxifloxacin and 34 (27.4%) were resistant to clindamycin, but all remained susceptible to metronidazole and vancomycin. Of 102 toxigenic isolates, 19 (18.7%) had an 18-bp deletion in the tcdC gene, eight (7.8%) a 39-bp deletion, and one (1.0%) a 54-bp deletion. Genes for binary toxin were present in 27 (21.8%). PCR-ribotype 027 was associated with older age (median age 83.5 vs. 65.5years, p < 0.0001) and longer duration of hospitalisation before onset of disease (median 15.5 vs. 9days, p = 0.014) with a trend towards higher crude mortality, more severe disease, and previous use of macrolides compared to ribotype non-027. Overall, severe disease correlated with use of a nasogastric tube and surprisingly shorter duration of hospitalisation before onset of disease. Today, laboratory-based and epidemiological surveillance systems are required to monitor CDAD cases and emergence of new epidemic strain

Not All Patients with Vancomycin-Resistant Enterococci Need To Be Isolated

Background. Vancomycin-resistant enterococci (VRE) have triggered multiple outbreaks. However, VRE of genotype vanC appear not to be associated with outbreaks. The goal of this study was to estimate the risk of bloodstream infections in patients colonized with VRE of genotype vanC who received care from a bone marrow transplant unit for patients with leukemia, where only standard precautions were implemented for VRE of genotype vanC during the last 9 years. Methods. Since 2000, all patients in the bone marrow transplant unit underwent routine VRE rectal screening, data were prospectively entered in a database, and isolates were molecularly characterized. Infection control policy required contact isolation for patients infected with VRE of genotype vanA or vanB but only standard precautions for patients infected with VRE of genotype vanC. Results. From January 2000 to July 2008, 290 isolates of VRE of genotype vanC obtained from 273 different patients were identified, with an incidence of 25-43 isolates/year. Of 290 isolates, 285 (98%) were identified in rectal screening swabs, 5 were from other body sites, and none required specific treatment. During the entire study period, only 1 case of bloodstream infection was detected, reflecting an incidence of 1 (0.4%) of the 273 patients, or <0.2 cases per 1000 patient-days. No outbreaks were recorded. Conclusions. These data provide strong evidence that carriers of VRE of genotype vanC do not require contact isolation, thereby saving resources and potentially improving patient care. The genotype should be routinely determined in areas with a high prevalence of VRE of genotype van

Highly effective regimen for decolonization of methicillin-resistant Staphylococcus aureus carriers

OBJECTIVE: To evaluate the efficacy of a standardized regimen for decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers and to identify factors influencing decolonization treatment failure. DESIGN: Prospective cohort study from January 2002 to April 2007, with a mean follow-up period of 36 months. SETTING: University hospital with 750 beds and 27,000 admissions/year. PATIENTS: Of 94 consecutive hospitalized patients with MRSA colonization or infection, 32 were excluded because of spontaneous loss of MRSA, contraindications, death, or refusal to participate. In 62 patients, decolonization treatment was completed. At least 6 body sites were screened for MRSA (including by use of rectal swabs) before the start of treatment. INTERVENTIONS: Standardized decolonization treatment consisted of mupirocin nasal ointment, chlorhexidine mouth rinse, and full-body wash with chlorhexidine soap for 5 days. Intestinal and urinary-tract colonization were treated with oral vancomycin and cotrimoxazole, respectively. Vaginal colonization was treated with povidone-iodine or, alternatively, with chlorhexidine ovula or octenidine solution. Other antibiotics were added to the regimen if treatment failed. Successful decolonization was considered to have been achieved if results were negative for 3 consecutive sets of cultures of more than 6 screening sites. RESULTS: The mean age (+/- standard deviation [SD]) age of the 62 patients was 66.2 +/- 19 years. The most frequent locations of MRSA colonization were the nose (42 patients [68%]), the throat (33 [53%]), perianal area (33 [53%]), rectum (36 [58%]), and inguinal area (30 [49%]). Decolonization was completed in 87% of patients after a mean (+/-SD) of 2.1 +/- 1.8 decolonization cycles (range, 1-10 cycles). Sixty-five percent of patients ultimately required peroral antibiotic treatment (vancomycin, 52%; cotrimoxazole, 27%; rifampin and fusidic acid, 18%). Decolonization was successful in 54 (87%) of the patie in the intent-to-treat analysis and in 51 (98%) of 52 patients in the on-treatment analysis. CONCLUSION: This standardized regimen for MRSA decolonization was highly effective in patients who completed the full decolonization treatment course

Highly Effective Regimen for Decolonization of Methicillin-Resistant Staphylococcus aureus Carriers

Objective. To evaluate the efficacy of a standardized regimen for decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers and to identify factors influencing decolonization treatment failure. Design. Prospective cohort study from January 2002 to April 2007, with a mean follow-up period of 36 months. Setting. University hospital with 750 beds and 27,000 admissions/year. Patients. Of 94 consecutive hospitalized patients with MRSA colonization or infection, 32 were excluded because of spontaneous loss of MRSA, contraindications, death, or refusal to participate. In 62 patients, decolonization treatment was completed. At least 6 body sites were screened for MRSA (including by use of rectal swabs) before the start of treatment. Interventions. Standardized decolonization treatment consisted of mupirocin nasal ointment, chlorhexidine mouth rinse, and full-body wash with chlorhexidine soap for 5 days. Intestinal and urinary-tract colonization were treated with oral vancomycin and cotrimoxazole, respectively. Vaginal colonization was treated with povidone-iodine or, alternatively, with chlorhexidine ovula or octenidine solution. Other antibiotics were added to the regimen if treatment failed. Successful decolonization was considered to have been achieved if results were negative for 3 consecutive sets of cultures of more than 6 screening sites. Results. The mean age (± standard deviation [SD]) age of the 62 patients was 66.2 ± 19 years. The most frequent locations of MRSA colonization were the nose (42 patients [68%]), the throat (33 [53%]), perianal area (33 [53%]), rectum (36 [58%]), and inguinal area (30 [49%]). Decolonization was completed in 87% of patients after a mean (±SD) of 2.1 ± 1.8 decolonization cycles (range, 1-10 cycles). Sixty-five percent of patients ultimately required peroral antibiotic treatment (vancomycin, 52%; cotrimoxazole, 27%; rifampin and fusidic acid, 18%). Decolonization was successful in 54 (87%) of the patients in the intent-to-treat analysis and in 51 (98%) of 52 patients in the on-treatment analysis. Conclusion. This standardized regimen for MRSA decolonization was highly effective in patients who completed the full decolonization treatment cours

Wafer-Scale Epitaxial Modulation of Quantum Dot Density

Precise control of the properties of semiconductor quantum dots (QDs) is vital for creating novel devices for quantum photonics and advanced opto-electronics. Suitable low QD-density for single QD devices and experiments are challenging to control during epitaxy and are typically found only in limited regions of the wafer. Here, we demonstrate how conventional molecular beam epitaxy (MBE) can be used to modulate the density of optically active QDs in one- and two- dimensional patterns, while still retaining excellent quality. We find that material thickness gradients during layer-by-layer growth result in surface roughness modulations across the whole wafer. Growth on such templates strongly influences the QD nucleation probability. We obtain density modulations between 1 and 10 QDs/${\mu}m^{2}$ and periods ranging from several millimeters down to at least a few hundred microns. This novel method is universal and expected to be applicable to a wide variety of different semiconductor material systems. We apply the method to enable growth of ultra-low noise QDs across an entire 3-inch semiconductor wafer

Wafer-scale epitaxial modulation of quantum dot density

Precise control of the properties of semiconductor quantum dots (QDs) is vital for creating novel devices for quantum photonics and advanced opto-electronics. Suitable low QD-densities for single QD devices and experiments are challenging to control during epitaxy and are typically found only in limited regions of the wafer. Here, we demonstrate how conventional molecular beam epitaxy (MBE) can be used to modulate the density of optically active QDs in one- and two- dimensional patterns, while still retaining excellent quality. We find that material thickness gradients during layer-by-layer growth result in surface roughness modulations across the whole wafer. Growth on such templates strongly influences the QD nucleation probability. We obtain density modulations between 1 and 10 QDs/µm2 and periods ranging from several millimeters down to at least a few hundred microns. This method is universal and expected to be applicable to a wide variety of different semiconductor material systems. We apply the method to enable growth of ultra-low noise QDs across an entire 3-inch semiconductor wafer

Purification, characterization, and cloning of a bifunctional molybdoenzyme with hydratase and alcohol dehydrogenase activity

A bifunctional hydratase/alcohol dehydrogenase was isolated from the cyclohexanol degrading bacterium Alicycliphilus denitrificans DSMZ 14773. The enzyme catalyzes the addition of water to α,β-unsaturated carbonyl compounds and the subsequent alcohol oxidation. The purified enzyme showed three subunits in SDS gel, and the gene sequence revealed that this enzyme belongs to the molybdopterin binding oxidoreductase family containing molybdopterins, FAD, and iron-sulfur clusters

Variation in the COVID-19 infection-fatality ratio by age, time, and geography during the pre-vaccine era: a systematic analysis

Background The infection-fatality ratio (IFR) is a metric that quantifies the likelihood of an individual dying once infected with a pathogen. Understanding the determinants of IFR variation for COVID-19, the disease caused by the SARS-CoV-2 virus, has direct implications for mitigation efforts with respect to clinical practice, non-pharmaceutical interventions, and the prioritisation of risk groups for targeted vaccine delivery. The IFR is also a crucial parameter in COVID-19 dynamic transmission models, providing a way to convert a population's mortality rate into an estimate of infections.Methods We estimated age-specific and all-age IFR by matching seroprevalence surveys to total COVID-19 mortality rates in a population. The term total COVID-19 mortality refers to an estimate of the total number of deaths directly attributable to COVID-19. After applying exclusion criteria to 5131 seroprevalence surveys, the IFR analyses were informed by 2073 all-age surveys and 718 age-specific surveys (3012 age-specific observations). When seroprevalence was reported by age group, we split total COVID-19 mortality into corresponding age groups using a Bayesian hierarchical model to characterise the non-linear age pattern of reported deaths for a given location. To remove the impact of vaccines on the estimated IFR age pattern, we excluded age-specific observations of seroprevalence and deaths that occurred after vaccines were introduced in a location. We estimated age-specific IFR with a non-linear meta-regression and used the resulting age pattern to standardise all-age IFR observations to the global age distribution. All IFR observations were adjusted for baseline and waning antibody-test sensitivity. We then modelled age-standardised IFR as a function of time, geography, and an ensemble of 100 of the top-performing covariate sets. The covariates included seven clinical predictors (eg, age-standardised obesity prevalence) and two measures of health system performance. Final estimates for 190 countries and territories, as well as subnational locations in 11 countries and territories, were obtained by predicting age-standardised IFR conditional on covariates and reversing the age standardisation.Findings We report IFR estimates for April 15, 2020, to January 1, 2021, the period before the introduction of vaccines and widespread evolution of variants. We found substantial heterogeneity in the IFR by age, location, and time. Age-specific IFR estimates form a J shape, with the lowest IFR occurring at age 7 years (0-0023%, 95% uncertainty interval [UI] 0-0015-0-0039) and increasing exponentially through ages 30 years (0-0573%, 0-0418-0-0870), 60 years (1-0035%, 0-7002-1-5727), and 90 years (20-3292%, 14-6888-28-9754). The countries with the highest IFR on July 15, 2020, were Portugal (2-085%, 0-946-4-395), Monaco (1-778%, 1-265-2-915), Japan (1-750%, 1-302-2-690), Spain (1-710%, 0-991-2-718), and Greece (1-637%, 1-155-2-678). All-age IFR varied by a factor of more than 30 among 190 countries and territories.After age standardisation, the countries with the highest IFR on July 15, 2020, were Peru (0-911%, 0-636-1-538), Portugal (0-850%, 0-386-1-793), Oman (0-762%, 0-381-1-399), Spain (0-751%, 0-435-1-193), and Mexico (0-717%, 0-426-1-404). Subnational locations with high IFRs also included hotspots in the UK and southern and eastern states of the USA. Sub-Saharan African countries and Asian countries generally had the lowest all-age and age-standardised IFRs. Population age structure accounted for 74% of logit-scale variation in IFRs estimated for 39 in-sample countries on July 15, 2020. A post-hoc analysis showed that high rates of transmission in the care home population might account for higher IFRs in some locations. Among all countries and territories, we found that the median IFR decreased from 0-466% (interquartile range 0-223-0-840) to 0-314% (0-143-0-551) between April 15, 2020, and Jan 1, 2021.Interpretation Estimating the IFR for global populations helps to identify relative vulnerabilities to COVID-19. Information about how IFR varies by age, time, and location informs clinical practice and non-pharmaceutical interventions like physical distancing measures, and underpins vaccine risk stratification. IFR and mortality risk form a J shape with respect to age, which previous research, such as that by Glynn and Moss in 2020, has identified to be a common pattern among infectious diseases. Understanding the experience of a population with COVID-19 mortality requires consideration for local factors; IFRs varied by a factor of more than 30 among 190 countries and territories in this analysis. In particular, the presence of elevated age-standardised IFRs in countries with well resourced health-care systems indicates that factors beyond health-care capacity are important. Potential extenuating circumstances include outbreaks among care home residents, variable burdens of severe cases, and the population prevalence of comorbid conditions that increase the severity of COVID-19 disease. During the pre-vaccine period, the estimated 33% decrease in median IFR over 8 months suggests that treatment for COVID-19 has improved over time. Estimating IFR for the pre-vaccine era provides an important baseline for describing the progression of COVID-19 mortality patterns.Funding Bill &amp; Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

Clinical features of patients with homozygous complement C4A or C4B deficiency

Introduction Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Material and methods Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Results Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%Cl = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%Cl = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%Cl = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%Cl = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%Cl = 1.22-4.88, p = 0.010). Conclusion This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.Peer reviewe