Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter–related infections (CRIs). Moreover, CRIs prolong ...hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.
•Safety, efficacy, and feasibility of antifungal prophylaxis and therapy of IFDs with novel posaconazole formulations could be demonstrated.•Stable posaconazole serum levels at steady-state could be ...shown.•Only a small number of adverse drug reactions rated as at least possibly associated with novel posaconazole formulations were documented.•Relatively high mortality rates in patients with posaconazole salvage therapy or due to rare invasive fungal infections could be shown.•This underlines the urgent need of appropriate empiric and targeted antifungal therapy with respect to both, clinical outcome and associated costs.
Novel formulations (gastro-resistant tablet and intravenous solution) of posaconazole (POS) have been approved in prophylaxis and therapy of invasive fungal diseases (IFDs). Study aim was to analyze treatment strategies and clinical effectiveness.
We set up a web-based registry on www.ClinicalSurveys.net for documentation of comprehensive data of patients who received novel POS formulations. Data analysis was split into two groups of patients who received novel POS formulations for antifungal prophylaxis (posaconazole prophylaxis group) and antifungal therapy (posaconazole therapy group), respectively.
Overall, 180 patients (151 in the posaconazole prophylaxis group and 29 in the posaconazole therapy group) from six German tertiary care centers and hospitalized between 05/2014 – 03/2016 were observed. Median age was 58 years (range: 19 – 77 years) and the most common risk factor for IFD was chemotherapy (n = 136; 76%). In the posaconazole prophylaxis group and posaconazole therapy group, median POS serum levels at steady-state were 1,068 μg/L (IQR 573–1,498 μg/L) and 904 μg/L (IQR 728–1,550 μg/L), respectively (P = 0.776). During antifungal prophylaxis with POS, nine (6%) probable/proven fungal breakthroughs were reported and overall survival rate of hospitalization was 86%. The median overall duration of POS therapy was 18 days (IQR: 7 – 23 days). Fourteen patients (48%) had progressive IFD under POS therapy, of these five patients (36%) died related to or likely related to IFD.
Our study demonstrates clinical effectiveness of antifungal prophylaxis with novel POS formulations. In patients treated for possible/probable/proven IFD, we observed considerable mortality in patients receiving salvage treatment and with infections due to rare fungal species.
Abstract
Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until ...September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets.
We reviewed the impact of antifungal prophylaxis with triazoles on drug–drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.
Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and
Pneumocystis jirovecii
pneumonia (PcP). As bacterial ...resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.
Phage Therapy in Germany-Update 2023 Willy, Christian; Bugert, Joachim J; Classen, Annika Y ...
Viruses,
02/2023, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and ...supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages.
Many haematology/oncology departments still provide a germ-free diet for neutropenic patients (neutropenic diet, ND) to minimise pathogen exposure, even though evidence on benefits is missing. We ...analysed the effects of a standard diet (SD) in neutropenic high-risk patients with cancer while focussing on infection-related outcomes.
Based on the Cologne Cohort of Neutropenic Patients, we conducted a propensity score–matched case-control study in haematological/oncological patients with a period of neutropenia longer than five days treated at our department between January 2004 and December 2012 (implementation of SD in January 2008). We assessed the association between an SD and selected infection-related end-points in an adjusted multivariable regression model and time-to-event analysis.
In total, 2086 neutropenic episodes (1043 per diet group) were included into analysis. The median days of neutropenia were 9 (interquartile range 7–16). The adjusted multivariable model revealed no association between the SD and severity and persistence of fever, death within 28 days, antibiotic treatment and weight loss >3 kg and a non-significant adjusted association between SD and duration of antibiotic treatment and blood stream infections. There was a significant association between SD and incidence of diarrhoea (odds ratio OR, 0.55; 95% confidence interval CI, 0.45–0.68; P < 0.001), nausea (OR, 0.53; 95% CI, 0.43–0.66; P < 0.001) and weight loss >1 kg (OR, 0.93; 95% CI, 0.89–0.98; P = 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were non-significant.
In our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points.
•The benefits of a germ-free diet for neutropenic patients with cancer are scarce.•Food restrictions may increase malnutrition and gastrointestinal side-effects.•Standard diets do not increase infectious complications in neutropenic patients.•Incidence of diarrhoea and nausea can be reduced by standard diets.•Implementation of standard diets for neutropenic patients with cancer is safe.
Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are ...single-centre experiences.
We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT).
The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111–2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis.
Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.
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•Letermovir prophylaxis after aHCT significantly improved survival.•The incidence of CMV infections was significantly reduced by letermovir.•Almost half of CMV infections occurred after letermovir discontinuation.•Neutropenia increased risk of CMV infections after letermovir discontinuation.
Background and purpose
During acute coronavirus disease 2019 (COVID‐19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating ...real‐world data from a multinational registry.
Methods
We analyzed COVID‐19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS‐Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression.
Results
A total of 6537 COVID‐19 patients (97.7% PCR‐confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio OR 1.42, 95% confidence interval CI 1.20–1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07–1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short‐term outcome of COVID‐19.
Conclusion
Our data on mostly hospitalized COVID‐19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short‐term outcome. ICB in critical COVID‐19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life‐threatening systemic viral infection.
We retrospectively analyzed data from 6537 predominantly hospitalized COVID‐19 patients registered in the European multinational Lean European Open Survey on SARS‐Infected Patients (LEOSS) registry between January 2020 and February 2021. Common neurological symptoms were excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%). Most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (2.2%) in patients with a complicated or critical disease course. Excessive tiredness (odds ratio OR 1.42) and prior neurodegenerative disease (OR 1.32) were associated with an increased risk of an unfavorable outcome.
Background. The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and ...1-y mortality of these patients. Methods. Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. Results. In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40–62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval 1.1-9.77; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 4–42 versus 11 3–21 d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 95% CI, 0.41-4.43, P = 0.618) did not differ between survivors and those who died. Conclusions. NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.
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