Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation

ABSTRACT

Introduction: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and microbiologically or clinically documented infections. Optimal duration of antimicrobial treatment is still unclear in these patients.

Areas covered: We provide an overview on the management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.

Expert opinion: Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam. Several clinical studies support the assumption that the primary antibiotic regimen might be safely discontinued prior to neutrophil reconstitution if the patient is afebrile for several days and all infection-related symptoms have been resolved. Primary empirical treatment with carbapenems or antibiotic combinations should commonly only be considered in selected patient subgroups, such as patients with severe neutropenic sepsis or colonization with multidrug-resistant bacteria. Preemptive antifungal treatment guided by lung imaging and other parameters (e.g. serial Aspergillus galactomannan antigen screening) might reduce the consumption of antifungals compared to the classical empirical approach.

Multidrug-resistant pathogens are emerging, and novel anti-infective agents under development are scarce. Therefore, a rational use of antimicrobials based on the principles of antibiotic stewardship is crucial.

KEYWORDS:

• Antibiotic stewardship
• de-escalation
• empirical treatment
• febrile neutropenia
• preemptive antifungal treatment

Article highlights

• Awareness of infections is crucial in patients with hematological and oncological diseases since symptoms might be masked and mimicked.

• Treatment delay may increase mortality. Thus, timely initiation of appropriate diagnostic measures and antimicrobial therapy is of utmost importance.

• A rational use of antimicrobials is urgently required to minimize the emergence of MDR bacteria and to reduce costs and side effects of these drugs.

• Single-agent anti-pseudomonal beta-lactam is the standard of care for high-risk FN. Selected patients with standard-risk FN might be treated on an outpatient basis if defined standard-risk criteria are fulfilled.

• Antimicrobial de-escalation and discontinuation should be considered whenever possible. Discontinuation of the primary antibiotic regimen prior to neutrophil reconstitution is considered to be safe if the patient is afebrile for several days and all clinical symptoms of infection have been resolved.

• The preemptive approach of antifungal therapy is adequate for clinically stable patients on mold-active antifungal prophylaxis. Clinically unstable patients not responding to first-line antibacterial treatment within a maximum of 72–96 h should be treated empirically with a mold-active antifungal.

Declaration of interest

M Schmidt-Hieber: received travel support by the AGIHO/DGHO. D Teschner: received honoraria for lectures from Gilead Sciences GmbH, MSD Sharp & Dohme GmbH, Pfizer Deutschland GmbH and travel support from the DGHO, Astellas Pharma GmbH, Celgene GmbH, Gilead Sciences GmbH, Jazz Pharmaceuticals Germany and MSD Sharp & Dohme GmbH, and has been an adviser to Gilead Sciences GmbH, MSD Sharp & Dohme GmbH, and Pfizer Deutschland GmbH. G Maschmeyer: received honoraria for lectures from Gilead Sciences GmbH, Pfizer Deutschland GmbH, Basilea Pharmaceutica and Astellas Pharma, Inc., and has been an adviser to Gilead Sciences GmbH. E Schalk: received travel support by the AGIHO/DGHO.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have a role in ongoing academic guidelines and reviews on de-escalation, and has acted as a lecturer for MSD and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.