Etiology of Febrile Neutropenia

Bacterial Pathogens

Bacterial pathogens are responsible for approximately 60-70% of microbiologically documented infections in febrile neutropenia, while fungi account for approximately 6-10% and viruses are occasional initial pathogens 1, 2
Gram-negative bacteria remain prominent causes of infection in febrile neutropenia, particularly as initial pathogens early in the course of fever and neutropenia 1, 2
Pseudomonas aeruginosa is a particularly concerning gram-negative pathogen due to high associated mortality 3, 4
Viridans group streptococci are common gram-positive pathogens in febrile neutropenia 1, 3
Enterococci, including vancomycin-resistant strains, are also common gram-positive pathogens 3, 5

Fungal infections typically occur later in the course of neutropenia, particularly after prolonged neutropenia and broad-spectrum antibiotic use 1, 2
Candida species are common fungal pathogens, particularly as a consequence of gastrointestinal mucositis 1
Aspergillus species and other filamentous fungi are important causes of morbidity and mortality in patients with severe and prolonged neutropenia 1, 2
Increasing numbers of infections with fluconazole-resistant Candida strains are being reported 5

Viruses are occasionally initial pathogens in febrile neutropenia 1, 2
Herpes simplex virus (HSV) is a common viral pathogen in febrile neutropenia 2, 6
Respiratory syncytial virus (RSV), parainfluenza virus, influenza A and B, and varicella zoster virus (VZV) are also common viral pathogens 1, 2, 6

Approximately 50-60% of patients who become febrile during neutropenia have an established or occult infection 1, 2
Roughly 10-20% of patients with neutrophil counts less than 100/mcL will develop a bloodstream infection 1, 2
Primary sites of infection are the alimentary tract, sinuses, lungs, and skin 1, 2
Mortality rates vary by pathogen, with gram-negative bacteremia associated with higher mortality (18%) compared to gram-positive bacteremia (5%) 5

Local epidemiology and resistance patterns should guide empiric antibiotic choices 5
The risk of infections is inversely proportional to the neutrophil count, with greatest risk when neutrophil count is less than 100/mcL 1, 2
Duration of neutropenia is a critical factor in determining infection risk and outcomes 1, 2
Chemotherapy-related gastrointestinal mucositis predisposes patients to bloodstream infections by viridans group streptococci, gram-negative rods, and Candida species 1