Clinical Characteristics and Optimization of Empirical Antimicrobial Therapy for Febrile Neutropenia in Patients With Hematologic Malignancies.

Abstract

Purpose: Since the publication of the 2011 Infectious Diseases Society of America (IDSA) guidelines for empirical treatment of febrile neutropenia (FN), there have been significant shifts in pathogen profiles and emerging challenges in treatment. These include increased prevalence of multidrug-resistant (MDR) bacteria and changes in the distribution of Gram-negative or Gram-positive bacteria (GPB). The study aims to update and optimize empirical treatment strategies for hematological malignancy (HM) patients, a population particularly vulnerable to these evolving threats.

Methods: A literature review was conducted on studies published between January 2010 and December 2023 regarding empirical treatment of FN in HM patients, focusing on pathogen characteristics, treatment regimens, and duration of therapy.

Results: Approximately one-third of HM patients with FN experience fever of unknown origin (FUO), while 40-50% have clinically documented infections (CDI), and 10-30% present with microbiologically documented infections (MDI), with a predominance of Gram-negative bacteria (GNB). Factors such as prolonged neutropenia, prior broad-spectrum antibiotic use, and previous infections with drug-resistant bacteria are associated with MDR infections. Cefepime, piperacillin/tazobactam (PTZ), and carbapenem are viable empirical treatments for high-risk HM patients, though cefepime monotherapy's advantage remains uncertain. In cases of pneumonia, shock, or suspected carbapenem-resistant infections, combination therapy, tigecycline, and newer antibiotics like ceftazidime/avibactam (CAZ/AVI) are often used. Empirical broad-spectrum antibiotics can be safely discontinued in FUO patients after 48 hours of clinical stability and apyrexia.

Conclusion: Proper selection of empirical antibiotics and determining optimal treatment duration are essential for reducing antibiotic resistance and improving outcomes in HM patients with FN. These findings underscore the need for updated clinical guidelines that address evolving pathogen profiles and the growing challenge of MDR infections.