Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 ...patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known.
We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients.
In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597).
Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.
Rifampicin in treating S aureus bacteraemia Rieg, Siegbert; Kern, Winfried V; Soriano, Alex
The Lancet (British edition),
08/2018, Letnik:
392, Številka:
10147
Journal Article
Recenzirano
Previous reports, including one clinical trial, showed that in meticillin-resistant S aureus bacteraemia, treatment with vancomycin plus rifampicin was associated with a worse outcome than ...monotherapy with vancomycin.2–4 A potential explanation is that vancomycin has a poor tissue distribution and rifampicin selects for strains with rpoB mutations, which have been implicated in reduced susceptibility to vancomycin.5 Second, on the basis of a European survey of treatment practice in uncomplicated S aureus bacteraemia,6 combination therapy is only rarely considered for these patients (unpublished data) and does not appear to be an important issue to most clinicians. The few patients with a deep infection focus or endocarditis included in the trial did substantially better with rifampicin (figure 2; figure 2a in the appendix).1 The potential benefit of rifampicin in the subgroup of patients with implant-associated infection has been suggested in a large observational study.7 Unfortunately, the ARREST trial cannot give definite answers in these difficult-to-treat scenarios because very few patients in the respective subgroups were included (of 758 ARREST patients, 14 2% had prosthetic heart valves or joints and 36 5% had implanted vascular devices). Considerable variation exists in clinical practice8,9 and in recommendations and guidance for treatment of S aureus bacteraemia, particularly with respect to how to manage patients with complicated disease. ...we need to improve the evidence base with studies considering specific subpopulations of patients with a higher risk of failure or recurrence, controlling the dose and the moment to start rifampicin, and deciphering the effect of the rifampicin partner drug.
Zusammenfassung
Rationale Antibiotikaverordnung ist zu einer Priorität in der medizinischen Fort- und Weiterbildung und Qualitätssicherung geworden. Optimierungsbereiche liegen vor allem in der ...kritischen Indikationsstellung, der vermehrten gezielten Therapie und Therapiedauerverkürzung. Sie betreffen niedergelassene Ärzte und auch die Krankenhausmedizin. Sie sind teilweise durch Defizite in der klinischen Forschung bedingt, aber auch Fehlentwicklungen in der fachärztlichen Weiterbildung, in der Strukturierung und im Vergütungssystem der verschiedenen Sektoren im Gesundheitssystem tragen zu Problemen in diesen Bereichen bei.
Antibiotic-Stewardship
(ABS)-Programme auf verschiedenen Ebenen können Maßnahmen zur Verbesserung der Antibiotika-Verordnungsqualität bündeln. Erfahrungen gibt es dazu vor allem bezüglich Schulung und Fortbildung von ärztlichem Personal und Apothekern sowie Etablierung von ABS-Teams vor Ort und von infektiologischen Konsiliardiensten im Krankenhaus. Eine gute Interaktion und Verzahnung mit der mikrobiologischen Diagnostik sind dabei wichtig und verstärken die Effekte auf die Verordnungsqualität. Notwendig sind politische Unterstützung und Investitionen, um solche neuen Strukturen nachhaltig etablieren zu können und diese auch für die Schnittstellen zwischen stationär und ambulant sowie für die ambulante Medizin weiterzuentwickeln.
Limited evidence on utilisation of health care by recently arrived asylum seekers and refugees in high-income countries is available. This study aims to describe the implementation of an integrated ...care facility (ICF) in an initial reception centre and measure the utilisation of care and the influence of operational parameters.
In a retrospective cohort study design, using medical records, we followed inhabitants of a reception centre in Germany between 11.10.2015 and 30.05.2018. We assessed frequency of visits and revisits to a newly established integrated care facility (ICF), and the effects of the ICF on visits to the local emergency department (LED) in the regional tertiary hospital using survival analysis and time series regression. We also explore the influence of operational parameters on the different implementation phases; phase 1: provisional clinic with 1-2 hours of physician presence daily, phase 2: implementation of ICF with 2-4 hours of care by a team of doctors and nurses daily, phase 3: routine running of ICF with daily operational hours of 10am-2pm with care provided by an interdisciplinary team of doctors and nurses.
14,419 total medical visits were recorded from 1,883 persons seeking health care in the ICF. The absolute number of visits per day remained similar over the study period (19·9/day), yet the relative number of visits changed from 2·2 to 15 per 100 inhabitants from phase 2 to 3, respectively. Most visits were due to respiratory infections (612/3080, 20%), and trauma and musculoskeletal conditions (441/3080, 14%). The rate of revisits to ICF was 2·9 per person per month (95%CI 2·9-3), more for those older, female, from North Africa and those with a translator present. The ratio of visits to the LED changed from 0·3/100 inhabitants per day to 0·14/100 inhabitants after implementation of the ICF and back to 0·3/100 inhabitants during the routine running.
Though seasonal variation and referral practices must be considered, a high rate of revisits to the ICF were recorded. While visits to the LED decreased after the implementation of the ICF, visits returned to the pre-ICF levels during the routine running of the ICF. The results show that AS&R require reliable access to health care, yet the needs of specific groups of migrants may be different, especially those with language barriers, minority groups or those from certain regions. As such, care should be migrant sensitive and adapt to the changing needs of the population. Though more research is required to better understand the differing needs of migrants, this study may help to inform guidelines surrounding migrant sensitive standards of care in Germany.
The predictive performance assessed with the area under the receiver operating characteristic curve (AUROC) was slightly lower in patients with cancer than in patients without cancer for the BLOOMY ...14-day mortality score (p=0·28; appendix), thus resembling the results obtained in the US cohort reported by Benzoni and colleagues. The prognostic performance of the quick SOFA (qSOFA) score was explored outside the intensive care unit (ICU) through a meta-analysis.2 When predicting in-hospital mortality, qSOFA had a pooled sensitivity of 51% (95% CI 39–62) and a pooled specificity of 83% (74–89). The discrimination for in-hospital mortality had an AUROC of 0·74 (95% CI 0·70–0·78).2 Similar findings were observed in patients with cancer in the ICU, for whom the AUROC did not exceed 0·76 for ICU mortality and 0·69 for hospital mortality.3 Another cohort study in a similar patient population found that qSOFA had a lower AUROC than SOFA (0·66 95% CI 0·56–0·75 vs 0·79 0·72–0·87) in predicting 30-day mortality.4 We agree with Benzoni and colleagues on the need for mortality scores to be validated in different subpopulations and especially in those who are immunocompromised.
SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in ...COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient's outcome.
Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design.
Inclusion criteria 1.Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR))2.Severe respiratory failure: a.Ambient air SpO
≤ 92% orb.Need of ≥ 6l O2/min orc.NIV (non-invasive ventilation) ord.IMV (invasive mechanical ventilation)3.Age ≥ 18 years Exclusion criteria 1.Non-invasive or invasive mechanical ventilation ≥ 48 hours2.Pregnancy or breast feeding3.Liver injury or failure (AST/ALT ≥ 5x ULN)4.Leukocytes < 2 × 10
/μl5.Thrombocytes < 50 × 10
/μl6.Severe bacterial infection (PCT > 3ng/ml)7.Acute or chronic diverticulitis8.Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine)9.Known active or chronic tuberculosis10.Known active or chronic viral hepatitis11.Known allergic reactions to tocilizumab or its ingredients12.Life expectation of less than 1 year (independent of COVID-19)13.Participation in any other interventional clinical trial within the last 30 days before the start of this trial14.Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed15.Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany.
Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment.
Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD's are counted as zero if the patient dies within the first 28 days.
The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS).
Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment.
100 participants will be randomised to each group (thus 200 participants in total).
Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020.
The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 2020).
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
During August–December 2022, toxigenic Corynebacterium diphtheriae was isolated from 25 refugees with skin infections and 2 refugees with asymptomatic throat colonization at a refugee reception ...center in Germany. None had systemic toxin-mediated illness. Of erosive/ulcerative skin infections, 96% were polymicrobial. Erosive/ulcerative wounds in refugees should undergo testing to rule out cutaneous diphtheria.
Rational prescription of antibiotics has become a priority in undergraduate and continued professional medical education and in quality management systems. Areas for optimization have been ...identified, above all, in critically establishing the indication for therapy, in increasing targeted therapy, and shortening treatment duration, and affect both outpatient and inpatient settings. They are partly related to deficiencies in clinical research, but aberrations in the development of the postgraduate training system, in the infrastructure, and in the reimbursement system of the various healthcare sectors in Germany contribute to problems in these areas. "Antibiotic stewardship" (ABS) programmes at different levels are capable of efficiently combining interventions to improve the quality of prescription. Progress has been made and experience gained in the professional training of physicians and pharmacists in antibiotic prescribing and with the hospital-wide establishment of ABS teams and specialist infectious disease consultation services. Close interaction and collaboration with diagnostic microbiology services are important and greatly enhance the impact of ABS programmes on the quality of prescription. Political support and investment are required for this new infrastructures to be sustainable and to further develop it for the cross-section between inpatients and outpatients, and for the outpatient setting.
Tick-borne encephalitis (TBE) caused by the tick-borne encephalitis virus (TBEV) is the most important tick-borne arboviral disease in Europe and Asia. The Upper Rhine Valley is thought to be the ...very western border of TBEV distribution in Europe. The aim of our study was to identify natural foci and isolate TBEV from ticks, to determine the prevalence of TBEV in local tick populations and to study the phylogenetic relatedness of circulating TBEV strains in this region.
Ticks were collected between 2016, 2017 and 2018 by flagging. TBEV was isolated from collected ticks and phylogenetic analyses were performed. Minimal infection rates (MIR) of the collected ticks were calculated.
At 12 sampling sites, a total of 4,064 Ixodes ticks were collected in 2016 and 2017 -(and one single collection 2018). 953 male, 856 female adult ticks and 2,255 nymphs were identified. The MIR rates were 0,17% (1/595) for Schiltach (Germany) and 0,11% (1/944) for Foret de la Robertsau (France), respectively. Overall, the three newly described TBEV strains, isolated in the years 2016 and 2017 from the Upper Rhine Valley have no close phylogenetic relation and show a genetic relationship with strains from eastern Europe. The 2018 TBEV strain from Aubachstrasse (Germany), however, is closely related to the TBEV found in Schiltach (Germany).
In conclusion, we demonstrate, to our knowledge for the first time, the phylogenetic relations of the newly isolated TBEV strains on both sides of the upper Rhine river.
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