Febrile neutropenia

Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. It is an oncologic emergency, and is the most common serious complication in patients with hematopoietic cancers or receiving chemotherapy for cancer. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia (bacteria in the bloodstream) is present in approximately 20% of all patients with this condition.

Febrile neutropenia or neutropenic fever is a defined as a single oral temperature value of ≥ 38.3 C (101 F) or a temperature ≥ 38 C (100.4 F) for ≥ 1 hour, with an absolute neutrophil count (ANC) < 1500 cell/microliter. In case of severe neutropenia, the ANC is < 500 cell/microliter. In profoundly severe neutropenia, the ANC is < 100 cells/microliter.

Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication of chemotherapy when it is myelosuppressive (suppresses the bone marrow from producing blood cells).^{[citation needed]} Febrile neutropenia is the most common and serious complication in patients with hematopoietic cancers or receiving chemotherapy for cancer. The condition occurs when a neutropenic patient gets infected by a pathogen. Approximately 50% of patients with febrile neutropenia develop an infection, of which 20% with profound neutropenia will develop bacteremia. Gram-positive bacteria are now the most common pathogens causing febrile neutropenia, with many of these infections resulting from long-term central venous catheters.

In patients with solid tumors, febrile neutropenia (FN) has a clinically identifiable focus in approximately 65% of episodes. However, microbiological documentation is achieved in only 20–30% of cases, and blood cultures are positive in 10–25%. The most frequent etiology is bacterial, involving both Gram-negative bacilli and Gram-positive cocci, with an approximate ratio of 3:2.

The selective pressures that favor Gram-positive infections in hematologic patients—such as central venous catheters, fluoroquinolone prophylaxis, grade 3–4 mucositis, or viral infections—are generally less intense in patients with solid tumors. Anaerobic or polymicrobial infections are uncommon but may occur in special circumstances, such as abscesses or enteritis.

In recent years, infections caused by resistant strains, particularly extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing bacteria, have increased. The risk of resistant microorganisms depends on previous colonization, invasive procedures, prior antibiotic exposure, recent hospitalization, chronic comorbidities, and local resistance patterns.

According to European surveillance data, resistance rates reported in 2015 for Gram-positive pathogens were 10–25% to macrolides among pneumococci, 25–50% resistance to cloxacillin among Staphylococcus aureus, up to 90% in coagulase-negative staphylococci, and 1–5% vancomycin resistance in Enterococcus faecium.

Invasive fungal infections (IFIs) are uncommon in patients with solid tumors (<8%). Risk factors for IFIs include prior antibiotic exposure, multiple lines of chemotherapy, prolonged corticosteroid use (≥20 mg/day prednisone equivalent for ≥4 weeks), extensive mucositis, central venous catheters, and prolonged neutropenia (>7 days). Candida albicans accounts for the majority of candidemia cases, though infections due to fluconazole-resistant species such as Candida krusei and Candida glabrata have become more frequent. Seasonal respiratory viruses are common in exposed contacts, but reactivation of latent viruses or those typically associated with acute leukemia or hematopoietic stem cell transplantation is rare among patients with solid tumors.