Chapter 47. Approach to Infection in Patients Receiving Cytotoxic Chemotherapy for Malignancy

• Risk of infection increases as the circulating absolute neutrophil count (ANC) declines below 1.0 × 109/L. The greatest risk of bacteremic infection occurs when the ANC is <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 is <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 (101°F) or more in the absence of other noninfectious causes of fever such as administration of blood products or pyrogenic drugs (e.g., cytotoxic therapy or 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 agents such as cotrimoxazole, norfloxacin, or ciprofloxacin 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 given acyclovir prophylaxis.
• Empiric antimicrobial therapy for suspected infection in the febrile neutropenic patient usually is composed of a broad-spectrum antibacterial regimen of an anti-pseudomonal penicillin or carbapenem administered as a single agent (monotherapy). Aminoglycoside-based combinations do not add to the efficacy of the single agent, but do add toxicity.
• Neutropenic patients responding to empiric antibacterial therapy generally require at least 5 days for the response to be observed in half the cases. Patients remaining febrile at 5 days should be systematically re-evaluated, while consideration of modification of the antimicrobial regimen can be made at day 7 or 8 unless clinical deterioration is evident. Glycopeptides administered as second-line empiric therapy for persistent fever after 3 to 5 days do not influence time to defervescence or febrile episode-related mortality.

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 immune deficiency syndromes such as congenital agammaglobulinemia, are susceptible to ...