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

Abstract

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.

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

“…In the case of neutropenia in the absence of septic shock, studies using modern broad-spectrum antibiotics consistently suggest that, while multidrug therapy to broaden pathogen coverage (e.g., to include Candida species) may be useful, combination therapy using a β-lactam and an aminoglycoside for purposes of accelerating pathogen clearance is not beneficial for less severely ill "low-risk" patients [187]. Combination therapy of this sort for even "high-risk" neutropenic patients (inclusive of hemodynamic instability and organ failure) with sepsis is inconsistently supported by several international expert groups [106,188]. This position against combination therapy for a single pathogen in any form of neutropenic infection emphatically does not preclude the use of multidrug therapy for the purpose of broadening the spectrum of antimicrobial treatment.…”

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

“…Antifungal prophylaxis has been adopted as a viable approach to prevent IFI and is currently recommended in high-risk patients [4][5][6]. In the current study, voriconazole for primary IFI prophylaxis demonstrated efficacy with a low rate of proven (2.4%) or probable (4.2%) episodes of IFI.…”

“…An episode of voriconazole prophylaxis was defined as voriconazole administration to a patient experiencing chemotherapy-induced neutropenia. Patients were considered to have neutropenia when laboratory values indicated an ANC less than 500 cells/ml [4,21]. Neutrophil recovery was defined as an ANC greater than 500 cells/ml for two consecutive days and progressing in an upward direction toward 1000 cells/ml of blood [4,21].…”

“…Individuals with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are at high-risk for developing an IFI following induction chemotherapy that results in prolonged and profound neutropenia [1][2][3]. Guidelines from the Infectious Diseases Society of America and National Comprehensive Care Network recommend consideration of antifungal prophylaxis against Aspergillus infection in patients >13 years of age who are undergoing intensive chemotherapy for AML or MDS [4][5][6].…”

“…A recent randomized, doubleblind trial demonstrated safety and efficacy of voriconazole prophylaxis in allogeneic hematopoietic cell transplant recipients; however, fungal-free survival, overall IFI, and invasive aspergillosis rates were similar to the comparator group managed with a preemptive screening strategy while receiving fluconazole prophylaxis [20]. The benefit of voriconazole prophylaxis in the non-stem cell transplant setting has not been established through randomized studies and remains controversial [4].…”