What are the most common microorganisms causing febrile neutropenia?

Most Common Microorganisms Causing Febrile Neutropenia

Gram-positive bacteria now account for 60-70% of microbiologically documented infections in febrile neutropenia, representing a shift from historical patterns, though gram-negative bacteria remain critically important due to their association with fulminant infections and high mortality. 1

Gram-Positive Pathogens (Most Common Overall)

The gram-positive organisms dominating current febrile neutropenia cases include:

• Coagulase-negative staphylococci are the most frequently isolated gram-positive pathogen, though these typically cause more indolent infections 1
• Staphylococcus aureus (including methicillin-resistant strains) causes potentially fulminant infections requiring prompt treatment 1
• Viridans group streptococci can cause severe, life-threatening infections particularly in patients with chemotherapy-induced mucositis 1
• Enterococcus species (including vancomycin-resistant strains) account for >50% of resistant isolates in some centers 1
• Streptococcus pneumoniae and Streptococcus pyogenes are less common but clinically significant 1

Critical Clinical Distinction

While gram-positive bacteria are numerically more common, many cause indolent infections (coagulase-negative staphylococci, vancomycin-resistant enterococci, Corynebacterium jeikeium) where a few days' delay in specific therapy may not be detrimental, though hospitalization may be prolonged. 1 However, S. aureus, viridans streptococci, and pneumococci can cause fulminant infections resulting in serious complications or death if not treated promptly. 1

Gram-Negative Pathogens (Highest Mortality Risk)

Despite being less common overall, gram-negative bacteria remain prominent causes requiring immediate empirical coverage:

• Escherichia coli is the most common gram-negative isolate and remains a prominent cause of bloodstream infection 1, 2
• Pseudomonas aeruginosa is particularly concerning due to high associated mortality and must be covered empirically 1, 2
• Klebsiella species are frequent pathogens, with increasing carbapenemase-producing strains reported 1
• Enterobacter species, Acinetobacter species, Stenotrophomonas maltophilia, and Citrobacter species are also documented causes 1

The rate of gram-negative infections is increasing in some centers, reversing the previous trend toward gram-positive predominance. 1

Fungal Pathogens (Late-Onset)

Fungi are rarely the cause of initial fever but emerge as important pathogens with specific timing:

• Candida species (primarily yeasts) typically appear after the first week of prolonged neutropenia and empirical antibiotic therapy, entering through chemotherapy-induced mucositis 1, 2
• Aspergillus species and other molds cause life-threatening infections of sinuses and lungs, typically after >2 weeks of neutropenia 1, 2

Viral Pathogens

• Herpes simplex virus (HSV) is a common viral pathogen 2
• Respiratory viruses including RSV, parainfluenza, and influenza A and B can cause neutropenic fever 2

Critical Context for Empirical Management

The majority of patients (50-60%) who develop fever during neutropenia have no identifiable site of infection and no positive culture results, yet empirical antibiotic therapy must be administered urgently (within 2 hours) because infection can progress rapidly. 1, 2

Common Pitfalls to Avoid

• Do not delay empirical antibiotics waiting for culture results—bacterial progression can be fulminant, particularly with gram-negative organisms 1
• Do not assume gram-positive coverage alone is sufficient despite their numerical predominance—gram-negative bacteria (especially P. aeruginosa) carry higher mortality risk and require immediate coverage 1
• Consider local antibiograms when selecting empirical regimens, as resistance patterns vary significantly by institution 1
• Recognize timing patterns: bacterial infections dominate early presentation, while fungal infections emerge after prolonged neutropenia (>7-14 days) 1, 2