Management of infection in immunocompromised patients

The number of immunosuppressed patients continues to increase worldwide. The main reasons are the demographic development and improved long-term survival, also for patients under immunosuppression. A major cause of hospitalization and mortality among these patients are infections. Their management, including prevention and adequate treatment, plays a crucial role in survival and quality of life, but also with regard to economic factors. Infection management in immunocompromised patients faces new challenges today. Not only the increasing number, but also new groups of patients at risk and an increasingly aging and comorbid population pose problems for the treating physicians. While cancer medicine is no longer determined solely by radiotherapy and chemotherapy, new targeted substances are playing an increasingly important role. In addition, new targeted substances complicate adequate infection prophylaxis due to potential interactions. The worldwide increase in antibiotic-resistant pathogens complicates treatment of bacterial infections, which is associated with increased mortality, especially in the immunocompromised patient population. Further, the disruption of the microbiome shows negative antibiotic-associated effects. Hence the reasonable use of anti-infectives in prophylaxis and therapy is of great importance. There are many recommendations and guidelines for clinicians regarding the management of infections in immunocompromised patients. Overlaps of infectiology, hygiene as well as hematology and oncology sometimes lead to different recommendations. This article provides an overview of the currently existing evidence and guidelines for infection management in immunosuppressed patients

Intravenous and tablet formulation of posaconazole in antifungal therapy and prophylaxis: A retrospective, non-interventional, multicenter analysis of hematological patients treated in tertiary-care hospitals

Objectives: 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. Methods: 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. Results: 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 mu g/L (IQR 573-1,498 mu g/L) and 904 mu g/L (IQR 728-1,550 mu g/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. Conclusions: 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. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Association between the dietary regimen and infection-related complications in neutropenic high-risk patients with cancer

Background: 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. Patients and methods: 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. Results: 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 1 kg (OR, 0.93; 95% CI, 0.89-0.98; P Z 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were nonsignificant. Conclusion: In our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points. (C) 2021 Elsevier Ltd. All rights reserved

The COVID-19 Pandemic as an Opportunity and Challenge for Registries in Health Services Research: Lessons Learned from the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS)

Zusammenfassung Ziel der Studie Aus der durch das Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) bedingten Coronavirus-Krankheit-2019 (COVID-19) haben sich Chancen und Herausforderungen fur den Aufbau von Registern in der Versorgungsforschung ergeben. Diese sollen exemplarisch am aktuell gro ss ten sektorenubergreifenden Register mit einem detaillierten klinischen Datensatz zu mit SARS-CoV-2 infizierten Patient:innen in Deutschland, der Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS), aufgezeigt werden. Methodik Ziele von LEOSS waren es, ein kollaboratives und integratives Register zur Erfassung von anonymen Daten aus der Versorgung zu schaffen und die Daten der Wissenschaft im Sinne eines Open Science Ansatzes rasch bereitzustellen. Alleiniges Einschlusskriterium war der virologische Nachweis von SARS-CoV-2. Schlusselstrategien waren die Reallokation der vorhandenen personellen und technischen Ressourcen, die fruhe und direkte Einbeziehung von Vertreter:innen des Datenschutzes und der Ethikkommissionen sowie die Entscheidung zu einem iterativen und agilen Entwicklungs- und Anpassungsprozess. Ergebnisse Getragen von den zahlreichen kollaborierenden Institutionen konnte ein transsektorales und internationales Netzwerk mit aktuell 133 aktiv rekrutierenden Standorten und 7227 dokumentierten Fallen aufgebaut werden (Stand 18.03.2021, ein Jahr seit Rekrutierungsstart von LEOSS). Die Nutzung der Daten wurde uber auf der Projektwebseite verfugbare Werkzeuge zur Datenexploration, wie auch uber die teilautomatisierte Bereitstellung von Datensatzen verschiedenen Umfangs, innerhalb kurzer Zeit ermoglicht. Es wurden 97 Antrage zur Datennutzung aus 27 Themengebieten begutachtet. Im Peer-Review-Verfahren wurden 9 Arbeiten in internationalen Fachzeitschriften veroffentlicht. Schlussfolgerung Mit LEOSS konnte in kurzester Zeit ein System zur Erfassung klinischer Verlaufsdaten zu COVID-19 in Deutschland etabliert werden. Auch wenn in anderen Projekten fur spezifische Fragestellungen weitaus gro ss ere Datenbestande durch direkten Zugriff auf Quellsysteme analysiert werden konnten, wurde durch den einheitlich gepflegten und technisch gepruften Dokumentationsstandard mit vielen fachspezifischen Details ein sehr gro ss er Datensatz mit wertvollen Alleinstellungsmerkmalen geschaffen. Aus den Erfahrungen von LEOSS konnen Implikationen fur die zukunftige Gestaltung von Registern und eine rasche Reaktion auf Pandemien abgeleitet werden. Abstract Objective The Coronavirus Disease-2019 (COVID-19) pandemic has brought opportunities and challenges, especially for health services research based on routine data. In this article we will demonstrate this by presenting lessons learned from establishing the currently largest registry in Germany providing a detailed clinical dataset on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients: the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS). Methods LEOSS is based on a collaborative and integrative research approach with anonymous recruitment and collection of routine data and the early provision of data in an open science context. The only requirement for inclusion was a SARS-CoV-2 infection confirmed by virological diagnosis. Crucial strategies to successfully realize the project included the dynamic reallocation of available staff and technical resources, an early and direct involvement of data protection experts and the ethics committee as well as the decision for an iterative and dynamic process of improvement and further development. Results Thanks to the commitment of numerous institutions, a transsectoral and transnational network of currently 133 actively recruiting sites with 7,227 documented cases could be established (status: 18.03.2021). Tools for data exploration on the project website, as well as the partially automated provision of datasets according to use cases with varying requirements, enabled us to utilize the data collected within a short period of time. Data use and access processes were carried out for 97 proposals assigned to 27 different research areas. So far, nine articles have been published in peer-reviewed international journals. Conclusion As a collaborative effort of the whole network, LEOSS developed into a large collection of clinical data on COVID-19 in Germany. Even though in other international projects, much larger data sets could be analysed to investigate specific research questions through direct access to source systems, the uniformly maintained and technically verified documentation standard with many discipline-specific details resulted in a large valuable data set with unique characteristics. The lessons learned while establishing LEOSS during the current pandemic have already created important implications for the design of future registries and for pandemic preparedness and response

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

Aims: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. Methods and results: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). Conclusions: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease. Graphic abstrac

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO)

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

Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

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

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort

Purpose Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. Methods 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). Conclusion In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients