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.

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

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

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

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

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for a range of malignant and nonmalignant disorders. Pre-transplant conditioning transiently ablates circulating granulocytes and monocytes and markedly increases susceptibility to disseminated infections [1, 2]. Mucosal barrier injury is also a complication of allo-HSCT and enables commensal microbes to invade underlying tissues and the bloodstream [3]. As a result, systemic bacterial infections are frequent during the early transplant period [4–6]. Vancomycin-resistant Enterococcus (VRE), viridians-group Streptococcus, and aerobic gram-negative bacteria are the most common causes of bloodstream infection following allo-HSCT [5–8]. Why some patients develop bacteremia while others do not is unclear.

The complex microbial populations colonizing the human intestine provide resistance to infection. The intestinal microbiota also serves as a sanctuary for highly antibiotic-resistant bacteria [9]. Prior studies using in vitro culture methods have characterized microbial populations inhabiting the intestine [10]; more recently, massively parallel pyrosequencing of bacterial 16S ribosomal RNA (rRNA) encoding genes has provided new insights into the composition and complexity of the intestinal microbiota by identifying bacterial taxons that are not readily cultivated in vitro [11–14]. These approaches have demonstrated the compositional changes and resilience of the intestinal microbiota of healthy individuals after antibiotic treatment [12]. Studies with mice demonstrated dramatic changes in the microbiota of the ileum and cecum following antibiotic treatment, and dramatic expansion of antibiotic-resistant microbes such as vancomycin-resistant Enterococcus (VRE) [15]. Intestinal expansion of VRE following antibiotic treatment is also seen in humans, with episodes of VRE domination in patients undergoing allo-HSCT preceding the development of VRE bacteremia in 2 patients [15].

Because the effect of allo-HSCT conditioning, prolonged neutropenia, and antibiotic administration on the gastrointestinal tract microbiota is unknown, we characterized the fecal microbiota of patients undergoing transplant at multiple time points using 454 pyrosequencing of 16S rRNA genes. (Data deposition: 454 pyrosequencing reads have been deposited in the National Center for Biotechnology Information Sequence Read Archive.)

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Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. Methods We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). Results An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, –20 percent; 95 percent confidence interval, –26 to –14 percent; P=0.001). The levofloxacin group had a lower rate of microbiological...

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A. Maria Nosari

Papers

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.