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

Walter T. Hughes, Donald Armstrong, Gerald P. Bodey, Eric J. Bow, Arthur E. Brown, Thierry Calandra, Ronald Feld, Philip A. Pizzo, Kenneth V. I. Rolston, Jerry L. Shenep, and Lowell S. Young St. Jude Children’s Research Hospital, Memphis, Tennessee; Memorial Sloan-Kettering Cancer Center, New York, New York; University of Texas M. D. Anderson Cancer Center, Houston; Harvard Medical School, Boston, Massachusetts; Stanford University School of Medicine, Palo Alto, and Kuzell Institute for Arthritis, San Francisco, California; University of Manitoba, Winnipeg, and Princess Margaret Hospital, Toronto, Canada; and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

/pdf/2002-guidelines-for-the-use-of-antimicrobial-agents-in-2br60wthls.pdf

2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer

Background Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections. Methods In this randomized, multicenter study involving evaluators who were unaware of treatment assignments, we compared the efficacy and safety of posaconazole with those of fluconazole or itraconazole as prophylaxis for patients with prolonged neutropenia. Patients received prophylaxis with each cycle of chemotherapy until recovery from neutropenia and complete remission, until occurrence of an invasive fungal infection, or for up to 12 weeks, whichever came first. We compared the incidence of proven or probable invasive fungal infections during treatment (the primary end point) between the posaconazole and fluconazole or itraconazole groups; death from any cause and time to death were secondary end points. Results A total of 304 patients were randomly assigned to receive posaconazole, and 298 ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa061094

Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia

https://www.uphs.upenn.edu/bugdrug/antibiotic_manual/oipreventidsacdcstemcell2009.pdf

Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective.

Peter G. Pappas, John H. Rex, Jack D. Sobel, Scott G. Filler, William E. Dismukes, Thomas J. Walsh, and John E. Edwards Division of Infectious Diseases, University of Alabama at Birmingham, Alabama; AstraZeneca Pharmaceuticals, Manchester, Great Britain; Wayne State University School of Medicine, Detroit, Michigan; Harbor–University of California-Los Angeles Medical Center, Torrance, California; and Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland

/pdf/guidelines-for-treatment-of-candidiasis-4yqbm9hcop.pdf

Guidelines for Treatment of Candidiasis

Background and Methods. Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. Results. By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P<0.001). Systemic fungal in...

https://www.nejm.org/doi/pdf/10.1056/NEJM199203263261301

A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation

OBJECTIVE To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.

Fluconazole prophylaxis of fungal infections in patients with acute leukemia: Results of a randomized placebo-controlled, double-blind, multicenter trial

Jeffrey L. Silber

Papers

A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation

Fluconazole prophylaxis of fungal infections in patients with acute leukemia: Results of a randomized placebo-controlled, double-blind, multicenter trial

Delayed consequences of therapy for childhood cancer.