From the Guidelines
Neutropenic fever is primarily caused by infections, particularly bacterial and fungal infections, in patients with neutropenia, and immediate empiric antibiotic therapy is essential to prevent major complications and mortality. The most common causes of neutropenic fever include bacterial infections, such as gram-negative organisms like Escherichia coli, Klebsiella, and Pseudomonas aeruginosa, as well as gram-positive bacteria like Staphylococcus and Streptococcus species 1. Fungal infections, especially Candida and Aspergillus species, become increasingly important in prolonged neutropenia. Viral infections like herpes simplex virus and cytomegalovirus can also trigger neutropenic fever.
Some key factors that contribute to the development of neutropenic fever include:
- The depth and duration of neutropenia, with the greatest risk occurring in patients who experience profound, prolonged neutropenia after chemotherapy 1
- The type of cancer treatment, particularly chemotherapy agents like cyclophosphamide, doxorubicin, and paclitaxel, which can suppress bone marrow function and cause neutropenia
- Hematologic malignancies themselves, which can directly cause neutropenia through bone marrow infiltration
When neutropenic fever occurs, immediate empiric antibiotic therapy is crucial, typically with broad-spectrum antibiotics like piperacillin-tazobactam, cefepime, or meropenem, to prevent major complications, such as hypotension, acute renal, respiratory, or heart failure, which can occur in approximately 25% to 30% of cases, and mortality, which can be as high as 11% 1. Treatment should continue until neutrophil recovery and resolution of symptoms, usually for at least 7 days. The urgency in treating neutropenic fever stems from neutrophils being the body's primary defense against infections, and their deficiency allows rapid progression of infections that can quickly become life-threatening without prompt intervention.
From the Research
Causes of Neutropenic Fever
- Neutropenic fever is a medical emergency that poses a significant morbidity and mortality risk to cancer patients receiving chemotherapy 2.
- Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients, and neutropenic fever may herald a life-threatening infection 3, 4.
- Cancer is associated with a variety of complications, including neutropenic fever, which can result in severe morbidity and mortality 5.
- Neutropenic fever is defined by fever with oral temperature >38.3°C or temperature >38.0°C for 1 hour with an absolute neutrophil count (ANC) < 1000 cells/microL, and patients who have received chemotherapy within 6 weeks of presentation are at high risk for neutropenia 5.
Risk Factors
- Patients with a known solid organ malignancy and a recorded diagnosis of neutropenic fever are at risk 2.
- The most common sites of infection in patients with neutropenic fever are the gastrointestinal tract, blood, skin, lung, and urinary tract 5.
- Physical examination and laboratory or imaging assessment may not display classic signs of infection in patients with neutropenic fever 5.
Importance of Prompt Treatment
- Prompt recognition of patients with neutropenic fever is imperative, and serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients 3, 4.
- Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death 3, 4.
- Rapid assessment and management are vital to improving outcomes in patients with suspected or confirmed neutropenic fever 5.