Aetiology
Fever in a neutropenic patient may be caused by a bacterial, viral, or fungal infection. Bloodstream infections are the most important and most commonly identified cause of fever in patients with febrile neutropenia.[14] However, a pathogen is only identified in approximately one third of patients. Host endogenous flora is often the primary source of causative pathogens.
Data indicate that gram-negative organisms are isolated at least as frequently, if not more so, as gram-positive organisms at many institutions, likely due to increasing antibiotic resistance.[15][16] The most common gram-negative organisms in this setting are Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa. The most common gram-positive organisms are coagulase-negative staphylococci, Staphylococcus aureus, viridans group streptococci, and Enterococcus species. Anaerobes are found in <5% of cases, but with the advent of advanced molecular techniques for microbial identification, it is anticipated that there will be an increase in reporting of microbiologically defined anaerobic bloodstream infections.
Fungi (predominantly Candida and Aspergillus species) are found in 2% to 10% of at-risk patients, particularly in those with concomitant corticosteroid use, those who are older, and those with relapsed or refractory haematological malignancy.[1][17] Importantly, the use of antifungal prophylaxis during the neutropenic period in certain high-risk populations has had a significant impact on reducing risk for fungal infection.[18]
Pathophysiology
Patients receiving cytotoxic chemotherapy may develop neutropenia as an adverse effect of treatment, which predisposes to infection.[19] Chemotherapy-induced myelosuppression is often the main mechanism causing neutropenia. Radiotherapy can also cause neutropenia by direct radiation damage to dividing myeloid stem and progenitor cells.
Mucosal breaches are an important route of entry for bacteria. This may occur due to damage of the endothelial lining caused by chemotherapy or radiotherapy (i.e., mucositis), and subsequent translocation of endogenous flora across the mucosa and into the bloodstream.[20] Bacteria or fungi (e.g., Candida) may also enter the bloodstream via indwelling catheters or implanted devices that have been colonised by endogenous flora, or from contamination during insertion, manipulation, or implantation.
Patients with haematological malignancies may have immune dysfunction (affecting both innate and adaptive immunity), allowing infections to progress unopposed. In patients with leukaemia or lymphoma, immune dysfunction may be linked to leukopenia (e.g., resulting from abnormal haematopoiesis and bone marrow dysfunction), hypogammaglobulinaemia, qualitative defects in neutrophil function (e.g., impaired chemotaxis and phagocytosis), or defective cell-mediated immunity. The degree and type of immune defect(s) are predictors of infection, with neutropenia classically a risk for bacterial and/or fungal infection, and concomitant defects in cell-mediated immunity (often related to chemotherapy) representing risk for fungal and/or viral infection.
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