Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases

Evaluation of Advanced Reverse Transcription-PCR Assays and an Alternative PCR Target Region for Detection of Severe Acute Respiratory Syndrome-Associated Coronavirus

First-generation reverse transcription-PCR (RT-PCR) assays for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) gave false-negative results in a considerable fraction of patients. In the present study, we evaluated two second-generation, replicase (R) gene-based, real-time RT-PCR test kits—the RealArt HPA coronavirus LC kit (Artus, Hamburg, Germany) and the LightCycler SARS-CoV quantification kit (Roche, Penzberg, Germany)—and a real-time RT-PCR assay for the nucleocapsid (N) gene. Detecting the N-gene RNA might be advantageous due to its high abundance in cells. The kits achieved sensitivities of 70.8% (Artus) and 67.1% (Roche) in 66 specimens from patients with confirmed SARS (samples primarily from the upper and lower respiratory tract and stool). The sensitivity of the N-gene assay was 74.2%. The differences in all of the sensitivities were not statistically significant (P = 0.680 [analysis of variance]). Culture cells initially contained five times more N- than R-gene RNA, but the respective levels converged during 4 days of virus replication. In clinical samples the median concentrations of R- and N-gene RNA, respectively, were 1.2 × 10(6) and 2.8 × 10(6) copies/ml (sputum and endotracheal aspirates), 4.3 × 10(4) and 5.5 × 10(4) copies/ml (stool), and 5.5 × 10(2) and 5.2 × 10(2) copies/sample (throat swabs and saliva). Differences between the samples types were significant but not between the types of target RNA. All (n = 12) samples from the lower respiratory tract tested positive in all tests. In conclusion, the novel assays are more sensitive than the first-generation tests, but they still do not allow a comprehensive ruling out of SARS. Methods for the routine sampling of sputum without infection risk are needed to improve SARS RT-PCR

Development and validation of BLOOMY prediction scores for 14-day and 6-month mortality in hospitalised adults with bloodstream infections: a multicentre, prospective, cohort study

Background: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. Methods: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. Findings: Between Feb 1, 2017, and Jan 31, 2019, 2568 (61·5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23·75% (95% CI 22·15-25·44; 610 of 2568 patients) and the 6-month mortality rate was 41·55% (39·54-43·59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0·873, 95% CI 0·849-0·896) and 6-month mortality (0·807, 0·784-0·831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61·32% (95% CI 51·81-70·04), a specificity of 86·36% (83·80-88·58), a positive predictive value (PPV) of 37·57% (30·70-44·99), and a negative predictive value (NPV) of 94·35% (92·42-95·80). The BLOOMY 6-month score showed a sensitivity of 69·93% (61·97-76·84), a specificity of 66·44% (61·86-70·73), a PPV of 40·82% (34·85-47·07), and a NPV of 86·97% (82·91-90·18). Interpretation: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections. Funding: DZIF German Center for Infection Research. Translation: For the German translation of the abstract see Supplementary Materials section

Increasing numbers and complexity of Staphylococcus aureus bloodstream infection - 14 years of prospective evaluation at a German tertiary care center with multi-center validation of findings

Objectives: Staphylococcus aureus bloodstream infection (SAB) is a common and severe infection. This study aims to describe temporal trends in numbers, epidemiological characteristics, clinical manifestations, and outcomes of SAB. Methods: We performed a post-hoc analysis of three prospective SAB cohorts at the University Medical Center Freiburg between 2006 and 2019. We validated our findings in a large German multi-center cohort of five tertiary care centers (R-Net consortium, 2017-2019). Time-dependent trends were estimated using Poisson or beta regression models. Results: We included 1,797 patients in the mono-centric and 2,336 patients in the multi-centric analysis. Overall, we observed an increasing number of SAB cases over 14 years (+6.4%/year and 1,000 patient days, 95%-CI: +5.1%-7.7%), paralleled by an increase in the proportion of community-acquired SAB (+4.9%/year (95%-CI: +2.1-7.8%), CA-SAB) and a decrease in the rate of methicillin-resistant-SAB (-8.5%/year (95%-CI: -11.2-(-5.6%)), MRSA-SAB). All of these findings were confirmed in the multi-center validation cohort (+6.2% cases per 1000 patient cases/year (95%-CI: -0.6-+12.6%), CA-SAB +8.7% (95%-CI: -1.2-+19.6%), MRSA-SAB -18.6% (95%-CI: -30.6-(-5.8%))). Moreover, we found an increasing proportion of patients with multiple risk factors for complicated/difficult-to-treat SAB (+8.5%/year, 95%-CI: +3.6-13.5%, p<0.001), alongside an overall higher level of comorbidities (Charlson comorbidity score +0.23 points/year, 95%-CI: +0.09-0.37, p=0.005). At the same time, the rate of deep-seated foci like osteomyelitis or deep-seated abscesses significantly increased (+6.7%, 95%-CI: +3.9-9.6%, p<0.001). A reduction of in-hospital mortality by 0.6% per year (95%-CI: 0.08-1%) was observed in the subgroup of patients with infectious diseases (ID) consultations. Conclusions: We found an increasing number of SAB combined with a significant increase in comorbidities and complicating factors in tertiary care centers. The resulting challenges in securing adequate SAB management in the face of high patient turnover will become an important task for physicians

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals

Vancomycin-resistant Enterococcus faecium colonizing patients on hospital admission in Germany: prevalence and molecular epidemiology

Objectives: To analyse the rectal carriage rate and the molecular epidemiology of vancomycin-resistant Enterococcus faecium (VREfm) recovered from patients upon hospital admission. Methods: Adult patients were screened at six German university hospitals from five different federal states upon hospital admission for rectal colonization with VREfm between 2014 and 2018. Molecular characterization of VREfm was performed by WGS followed by MLST and core-genome MLST analysis. Results: Of 16350 patients recruited, 263 were colonized with VREfm, with increasing prevalence rates during the 5year study period (from 0.8% to 2.6%). In total, 78.5% of the VREfm were vanB positive and 20.2% vanA positive, while 1.2% harboured both vanA and vanB. The predominant ST was ST117 (56.7%) followed by ST80 (15%), ST203 (10.9%), ST78 (5.7%) and ST17 (3.2%). ST117/vanB VREfm isolates formed a large cluster of 96 closely related isolates extending across all six study centres and four smaller clusters comprising 13, 5, 4 and 3 isolates each. In contrast, among the other STs inter-regional clonal relatedness was rarely observed. Conclusions: To our knowledge, this is the largest admission prevalence and molecular epidemiology study of VREfm. These data provide insight into the epidemiology of VREfm at six German university hospitals and demonstrate the remarkable inter-regional clonal expansion of the ST117/vanB VREfm clone

Resolving colistin resistance and heteroresistance in Enterobacter species

Taxonomical complexity has muddled the classification of clinically relevant Enterobacter species. Authors carry out a genome-based study on clinical isolates to investigate colistin resistance and heteroresistance in Enterobacter