Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Infect Dis. Aug 25, 2016; 6(3): 37-60
Published online Aug 25, 2016. doi: 10.5495/wjcid.v6.i3.37
Clinical research in febrile neutropenia in cancer patients: Past achievements and perspectives for the future
Jean Klastersky, Marianne Paesmans, Michel Aoun, Aspasia Georgala, Angela Loizidou, Yassine Lalami, Lissandra Dal Lago
Jean Klastersky, Marianne Paesmans, Michel Aoun, Aspasia Georgala, Angela Loizidou, Yassine Lalami, Lissandra Dal Lago, Institut Jules Bordet, Service de Médecine, Centre des Tumeurs de l’Université Libre de Bruxelles, 1000 Brussels, Belgium
Author contributions: Klastersky J contributed to historical background and introduction; Paesmans M contributed to risk prediction for complications and death; Klastersky J contributed to prevention according to risk; Aoun M contributed to empiric therapy according to risk; Georgala A contributed to emergence of resistant strains; Loizidou A contributed to persisting febrile neutropenia; Lalami Y contributed to cost issues; Dal Lago L contributed to febrile neutropenia at the extreme of age; Klastersky J and Aoun M contributed to conclusion.
Conflict-of-interest statement: None of the authors has any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Jean Klastersky, MD, PhD, Institut Jules Bordet, Service de Médecine, Centre des Tumeurs de l’Université Libre de Bruxelles, 1, rue Héger-Bordet, 1000 Brussels, Belgium.
Telephone: +32-2-5417396 Fax: +32-2-5380858
Received: June 30, 2015
Peer-review started: July 6, 2015
First decision: September 30, 2015
Revised: April 25, 2016
Accepted: June 1, 2016
Article in press: June 3, 2016
Published online: August 25, 2016

Febrile neutropenia (FN) is responsible for significant morbidity and mortality. It can also be the reason for delaying or changing potentially effective treatments and generates substantial costs. It has been recognized for more than 50 years that empirical administration of broad spectrum antibiotics to patients with FN was associated with much improved outcomes; that has become a paradigm of management. Increase in the incidence of microorganisms resistant to many antibiotics represents a challenge for the empirical antimicrobial treatment and is a reason why antibiotics should not be used for the prevention of neutropenia. Prevention of neutropenia is best performed with the use of granulocyte colony-stimulating factors (G-CSFs). Prophylactic administration of G-CSFs significantly reduces the risk of developing FN and consequently the complications linked to that condition; moreover, the administration of G-CSF is associated with few complications, most of which are not severe. The most common reason for not using G-CSF as a prophylaxis of FN is the relatively high cost. If FN occurs, in spite of prophylaxis, empirical therapy with broad spectrum antibiotics is mandatory. However it should be adjusted to the risk of complications as established by reliable predictive instruments such as the Multinational Association for Supportive Care in Cancer. Patients predicted at a low level of risk of serious complications, can generally be treated with orally administered antibiotics and as out-patients. Patients with a high risk of complications should be hospitalized and treated intravenously. A short period of time between the onset of FN and beginning of empirical therapy is crucial in those patients. Persisting fever in spite of antimicrobial therapy in neutropenic patients requires a special diagnostic attention, since invasive fungal infection is a possible cause for it and might require the use of empirical antifungal therapy.

Keywords: Fever, Neutropenia, Prophylaxis, Algorithm, Cancer

Core tip: The overall presentation of febrile neutropenia has considerably changed over the last 50 years. Prevention is now feasible with the use of granulocyte colony stimulating factors. If fever appears in a neutropenic patient, empirical therapy with broad spectrum antibiotics is mandatory; it should be adapted to the risk of severe complications that can be now predicted in individual patients using a reliable scoring system. Special situations such as persisting fever in neutropenic patients, the risk of invasive fungal infection and the management of older patients are crucial questions that are discussed as well as the issues linked to the high cost of prophylaxis and therapy.