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  • Risk of infection increases as the circulating absolute neutrophil count (ANC) declines below 1.0 and 0.5 × 109/L. The greatest risk of bacteremic infection occurs when the ANC < 0.1 × 109/L.

  • Cytotoxic therapy for remission-induction therapy for acute myeloid leukemia or conditioning therapy for bone marrow transplantation (high-risk patients) is associated with periods when the ANC < 0.1 × 109/L for 14 to 21 days. The time to marrow recovery (ANC > 0.5 × 109/L) can vary from 21 to 42 days.

  • Intermittent administration of cytotoxic therapy for solid tissue malignancies or lymphoreticular malignancies (low-risk patients) is often associated with a neutrophil nadir at 10 to 14 days from beginning treatment and with periods of neutropenia (ANC < 0.5 × 109/L) of less than 5 to 7 days. This pattern of neutrophil recovery influences the natural history of febrile neutropenic episodes.

  • Febrile episodes during neutropenia are defined by an oral temperature of ≥38.3°C (100°F) in the absence of other noninfectious causes of fever such as administration of blood products or pyrogenic drugs (eg, cytotoxic therapy, amphotericin B), the underlying disease, thromboembolic or thrombophlebitic events, or hemorrhagic events.

  • A single neutropenic episode may be characterized by one or more febrile episodes, of which one or more may represent infections.

  • Body sites most often associated with infection in the neutropenic patient are those associated with integumental surfaces (skin, upper and lower respiratory tract, and upper and lower gastrointestinal tract).

  • Antibacterial prophylaxis with oral fluoroquinolone agents such as ciprofloxacin or levofloxacin can reduce the frequency of febrile episodes and bacteremic events in patients with protracted neutropenia.

  • Patients undergoing remission-induction for acute myeloid leukemia or bone marrow transplantation with a history of herpetic stomatitis or who are IgG-seropositive for herpes simplex virus (HSV) are at risk for severe herpetic mucositis. Such patients should be considered for oral nucleoside analogue-based acyclovir antiviral prophylaxis.

  • The recommended initial empirical antibacterial therapy for suspected infection in the febrile neutropenic patient is a broad-spectrum antibacterial regimen of an antipseudomonal penicillin or carbapenem administered as a single agent (monotherapy). Additional initial antibacterial agents such as the aminoglycosides, fluoroquinolones, or vancomycin may be indicated for the initial management of severe sepsis/septic shock, pneumonia, or where antimicrobial resistance is suspected.

  • The median time-to-defervescence for febrile neutropenic patients at low and high risk for medical complications is 3 and 5 days, respectively. Immune augmenting anticancer therapies such as chimeric antigen receptor T-cells (CAR-T) or the checkpoint inhibitors may generate T-lymphocyte-mediated sepsis-like syndromes that require immune suppression to control. Infection risk is enhanced by the immune suppressive therapy.


Critical care physicians are often called on to provide metabolic, hemodynamic, and respiratory support for patients with various inherited or acquired defects in host defense that render them susceptible to potentially lethal infections. Patients with single host defense system defects, such as those with inherited ...

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