What percentage of febrile neutropenia cases are caused by bacteria, fungi, and viruses respectively?

Etiology of Febrile Neutropenia: Bacterial, Fungal, and Viral Causes

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

Bacterial Pathogens (60-70%)

Gram-Negative Bacteria (50-70% of bacterial infections)

• Gram-negative bacteria remain prominent causes of infection in febrile neutropenia, particularly as initial pathogens early in the course of fever and neutropenia 1
• Common gram-negative pathogens include:
  • Escherichia coli (most common gram-negative isolate in many studies) 2, 3
  • Klebsiella species 1, 2
  • Pseudomonas aeruginosa (particularly concerning due to high associated mortality) 1
  • Enterobacter species 1
  • Acinetobacter species 4
  • Stenotrophomonas maltophilia 1

Gram-Positive Bacteria (30-50% of bacterial infections)

• There has been a shift toward gram-positive infections over the past decades, likely due to long-dwelling intravascular devices, fluoroquinolone prophylaxis, and high-dose chemotherapy-induced mucositis 5
• Common gram-positive pathogens include:
  • Coagulase-negative staphylococci (most common gram-positive isolate) 4, 6
  • Staphylococcus aureus 1, 4
  • Viridans group streptococci 1
  • Enterococci, including vancomycin-resistant strains 1
  • Streptococcus pneumoniae 1

Fungal Pathogens (6-10%)

• Fungal infections typically occur later in the course of neutropenia, particularly after prolonged neutropenia and broad-spectrum antibiotic use 1
• Common fungal pathogens include:
  • Candida species (particularly as a consequence of gastrointestinal mucositis) 1, 3
  • Aspergillus species and other filamentous fungi (important cause of morbidity and mortality in patients with severe and prolonged neutropenia) 1
  • Increasing numbers of infections with fluconazole-resistant Candida strains (e.g., Candida krusei and Candida glabrata) 1

Viral Pathogens (Occasional)

• Viruses are occasionally initial pathogens in febrile neutropenia 1
• Common viral pathogens include:
  • Herpes simplex virus (HSV) 1
  • Respiratory syncytial virus (RSV) 1
  • Parainfluenza virus 1
  • Influenza A and B 1
  • Varicella zoster virus (VZV) 1

Changing Epidemiology

• The epidemiology of infections in febrile neutropenia has changed over time:
  • Twenty years ago, gram-negative bacteria caused approximately 70% of bloodstream infections 5
  • In some centers today, gram-positive cocci account for approximately 70% of bacteremic isolates 5
  • However, recent studies suggest a possible shift back toward gram-negative predominance in some regions 2, 3

Clinical Implications

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

Important Considerations

• Local epidemiology and resistance patterns should guide empiric antibiotic choices 1, 4
• The risk of infections is inversely proportional to the neutrophil count, with greatest risk when neutrophil count is less than 100/mcL 1
• Duration of neutropenia is a critical factor in determining infection risk and outcomes 1
• Chemotherapy-related gastrointestinal mucositis predisposes patients to bloodstream infections by viridans group streptococci, gram-negative rods, and Candida species 1