Key Points
➤ Patients undergoing cytotoxic chemotherapy and hematopoietic stem cell
transplant are at risk for infection, particularly during the period of neutropenia.
➤ The risk of infection increases with the depth and duration of neutropenia, with
the greatest risk occurring in patients who experience profound, prolonged
neutropenia after chemotherapy, which is most likely to occur in the period prior
to engraftment during hematopoietic cell transplantation and following induction
chemotherapy for acute leukemia.
➤ Fever can be an important indicator and is often the only sign or symptom of
infection although clinicians should also be mindful that severely or profoundly
neutropenic patients may present with suspected infection in an afebrile state,
or even hypothermic.
➤ Prevention and appropriate management of febrile neutropenia (FN) is important
because the rate of major complications (e.g. hypotension, acute renal,
respiratory or heart failure) in the context of FN is approximately 25–30%, and
mortality up to 11%. In the setting of severe sepsis or septic shock the hospital
mortality rate may be as high as 50%.
1. Carmona-Bayonas A, Jimenez-Fonseca P, Virizuela Echaburu J, et al: Prediction of serious complications
in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile
Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol 33:465-71, 2015.
2. Kuderer NM, Dale DC, Crawford J, et al: Mortality, morbidity, and cost associated with febrile neutropenia
in adult cancer patients. Cancer 106:2258-66, 2006.
3. Legrand M, Max A, Peigne V, et al: Survival in neutropenic patients with severe sepsis or septic shock.
Crit Care Med 40:43-9, 2012.
Antimicrobial Prophylaxis
➤ Risk of febrile neutropenia should be systematically assessed (in consultation
with infectious disease specialists as needed), including patient-, cancer- and
treatment-related factors (see Table 1). (Strong Recommendation; EB-B-I)
➤ Antibiotic prophylaxis with a fluoroquinolone is recommended for patients who
are at high risk for febrile neutropenia or profound, protracted neutropenia
(e.g. most patients with acute myeloid leukemia/myelodysplastic syndromes
(AML/MDS), or hematopoietic stem cell transplantation (HSCT) treated with
myeloablative conditioning regimens). Antibiotic prophylaxis is not routinely
recommended for patients with solid tumors. (Moderate Recommendation;
EB-B-H)
➤ Antifungal prophylaxis with an oral triazole or parenteral echinocandin is
recommended for patients at risk for profound, protracted neutropenia, such as
most patients with AML/MDS or HSCT. Antifungal prophylaxis is not routinely
recommended for patients with solid tumors. Further distinctions between
recommendations for invasive candidiasis and invasive mold infection are
provided within the full text of the guideline. (Moderate Recommendation;
EB-B-I)
