BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

http://bibliotecadigital.udea.edu.co/bitstream/10495/24087/1/RestrepoAngela_2008_DefinitionsInvasiveCancer.pdf

Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

https://link.springer.com/content/pdf/10.1007%2Fs00134-017-4683-6.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

The aim of broth and agar dilution methods is to determine the lowest concentration of the assayed antimicrobial agent (minimal inhibitory concentration, MIC) that, under defined test conditions, inhibits the visible growth of the bacterium being investigated. MIC values are used to determine susceptibilities of bacteria to drugs and also to evaluate the activity of new antimicrobial agents. Agar dilution involves the incorporation of different concentrations of the antimicrobial substance into a nutrient agar medium followed by the application of a standardized number of cells to the surface of the agar plate. For broth dilution, often determined in 96-well microtiter plate format, bacteria are inoculated into a liquid growth medium in the presence of different concentrations of an antimicrobial agent. Growth is assessed after incubation for a defined period of time (16-20 h) and the MIC value is read. This protocol applies only to aerobic bacteria and can be completed in 3 d.

Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances

Infectious Diseases Society of America.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

/pdf/clinical-practice-guideline-for-the-use-of-antimicrobial-1cdrjevze2.pdf

Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America

False-positive tests for Aspergillus galactomannan have been reported in neutropenic patients. We failed to detect any circulating antigen during the 2 weeks following allogeneic haematopoietic stem cell transplantation of 12 patients who had severe mucositis but were unable to eat.

Aspergillus galactomannan antigen levels in allogeneic haematopoietic stem cell transplant recipients given total parenteral nutrition.

A cohort of 439 haematopoietic SCT recipients was analysed to determine the incidence of Gram-positive coccal bacteraemia and thromboembolic events associated with the use of central venous catheters (CVCs) and to determine risk factors for these complications. The incidences of persistent coagulase-negative staphylococcal (CoNS) bacteraemia, symptomatic thrombosis and thrombophlebitis were 25%, 9.6% and 6.6%, respectively. Duration of neutropenia (in days, odds ratio (OR) 1.02; P=0.04) and left-sided placement of the CVCs (OR 1.73; P=0.03) were independent risk factors for the occurrence of persistent CoNS bacteraemia, whereas the use of less mucotoxic conditioning regimens was associated with a lower risk (high-dose melphalan (HDM)/BEAM vs other regimens, OR 0.24; P<0.001). Use of TBI, persistent CoNS bacteraemia and tip colonisation were all significantly associated with an increased risk of symptomatic thrombosis (OR 6.03, 3.36 and 2.80, respectively; P0.02). The risk factors found in this cohort of SCT recipients differed from those found in the general cancer population, showing an important role for persisting bacteraemia in the pathogenesis of CVC-associated thrombosis. Therefore, we constructed a new algorithm in order to improve catheter management and prevent these CVC-related complications.

Incidence of and risk factors for persistent gram-positive bacteraemia and catheter-related thrombosis in haematopoietic stem cell transplantation

/pdf/pneumocystis-jirovecii-pneumonia-still-a-concern-in-patients-2qcqz2m83j.pdf

J.P. Donnelly

Papers

Aspergillus galactomannan antigen levels in allogeneic haematopoietic stem cell transplant recipients given total parenteral nutrition.

Incidence of and risk factors for persistent gram-positive bacteraemia and catheter-related thrombosis in haematopoietic stem cell transplantation

Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients-authors' response.

Aspergillus infections: problems in diagnosis and treatment

Triggers for driving treatment of at-risk patients with invasive fungal disease.