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

In a prospective randomized study, 90 granulocytopenic febrile patients presenting with a localized infection were treated empirically with ceftazidime alone or in combination with amikacin (1.5 g/day). Two thirds had received selective oral antimicrobial prophylaxis before therapy. The treatment groups were comparable in terms of the depth and duration of granulocytopenia as well the distribution of the infection categories and rate of bacteremia. There was no difference with respect to the final response: 53% for the monotherapy group versus 48% for the combination group, and both regimens appeared to be equally safe. The duration of fever, clinical symptoms, antibiotic therapy, and granulocytopenia were comparable for both treatment groups, and approximately 90% of patients survived the infection. Only one patient given monotherapy required amikacin. It is concluded that aminoglycosides are not necessary for the empiric treatment of infectious complications in granulocytopenic patients if antibacterial prophylaxis has been given before-hand.

Ceftazidime with or without amikacin for the empiric treatment of localized infections in febrile, granulocytopenic patients.

Empiric therapy is necessary for febrile, neutropenic patients in order to minimise morbidity and mortality. Certain agents are now available for monotherapy which offcrcomparable success to combinations of either an aminoglycoside with a β-lactam or two β-lactams. However, no regimen offers complete treatment under all circumstances in all patients. It is also apparent that febrile, neutropenic patients comprise a more heterogeneous group than just those with bacteraemia, clinically apparent infection and unexplained fever. Localized infections occur in just under a third of cases at the onset of fever and a similar number will develop during the course of fever. Mortality is higher in infections that are accompanied by bacteraemia and also those that develop subsequently, especially when related to the lung. The aetiological agent also differs with each type of infection as does the duration of fever and symptoms. Consequently modifications are required more often. The length of treatment may also diffe...

Empiric treatment of localized infections in the febrile neutropenic patient with monotherapy.

In a randomized study comparing cotrimoxazole plus colistin with ciprofloxacin, each in combination with nonabsorbable antimycotics, the incidence of major infections in terms of septicemias and pneumonias as well as of minor infections and episodes of unexplained fever (FUO) was higher in patients treated with ciprofloxacin. In cases of microbiologically documented infections, gram-positive cocci dominated by far. In surveillance cultures of oral washings and of feces, gram-negative enterobacteria were only rarely detected; however, large numbers of cultures were positive for Acinetobacter species. There were four cases of documented Pneumocystis carinii pneumonia in patients not receiving cotrimoxazole. The incidence of documented mycotic infections as well as the detection of fungi in surveillance cultures was similar in both treatment groups. A decrease in the number of adverse events, especially of allergic reactions, could not be achieved by the administration of ciprofloxacin. In conclusion, cotrimoxazole plus colistin in combination with nonabsorbable antimycotics remains the standard regimen for prevention of infection in patients with acute leukemia undergoing aggressive remission induction therapy. A detailed analysis of study II will be prepared for publication.

Prevention of infection in acute leukemia.

Blennow and Mattsson1 recently concluded in a reply to Meije et al.2 that standardization of Aspergillus PCR diagnosis is needed. We agree with this, which is why we set up a Working Group of the International Society of Human and Animal Mycology, known as the European Aspergillus PCR initiative (EAPCRI) (http://www.eapcri.eu). This group has forged ahead, developing the necessary framework for establishing standards.3

J.P. Donnelly

Papers

Ceftazidime with or without amikacin for the empiric treatment of localized infections in febrile, granulocytopenic patients.

Empiric treatment of localized infections in the febrile neutropenic patient with monotherapy.

Prevention of infection in acute leukemia.

Standardization of Aspergillus PCR diagnosis

Aspergillus fumigatus Pneumonia in Neutropenic Patients During Therapy with Fluconazole for Infection Due to Candida Species