Infectious Disease· Topic 7.13 Bacteremia, sepsis, and occult deep-seated infection· 7.13.5

Neutropenic fever

Neutropenic fever is an oncologic emergency defined as a single oral temperature of 38.3 C or higher, or 38.0 C sustained for 1 hour, with an ANC of 500/microL or lower, most often during the chemotherapy nadir. Management is empiric antipseudomonal beta-lactam therapy within 60 minutes, with vancomycin, antifungal therapy, and growth factors added only for specific indications.

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What this article covers

  • Overview

    Definition: neutropenic fever is a fever in a patient with a dangerously low ANC, signaling that the barrier against invading organisms has failed and infection can progress to sepsis within hours.

  • Epidemiology

    Chemotherapy is the dominant cause: most episodes follow cytotoxic chemotherapy for a hematologic malignancy or solid tumor, with risk depending on regimen intensity.

  • Risk factors

    Depth and duration of neutropenia: ANC at or below 100/microL and anticipated neutropenia longer than 7 days (typical of leukemia/lymphoma induction) confer the highest infection risk and are contraindications to outpatient management.

  • Pathophysiology

    Loss of the neutrophil barrier: chemotherapy-induced myelosuppression removes the primary cellular defense against bacterial and fungal invasion, so contained organisms can proliferate and disseminate.

  • Clinical features

    Fever as the presenting and often only sign: because neutrophils cannot generate a normal inflammatory response, patients may lack localizing pain, purulence, or swelling even with an established…

  • Differential diagnosis

    Progressive or uncontrolled underlying malignancy (tumor fever): fever from the malignancy itself; a diagnosis of exclusion made only after a thorough infectious workup is negative and the patient remains stable off antibiotics.

  • Diagnosis

    Establish the diagnosis by definition, not by a test: a single oral temperature of 38.3 C (101 F) or higher on one occasion, or 38.0 C (100.4 F) or higher sustained for at least 1 hour (or on two…

  • Management

    Start empiric broad-spectrum antipseudomonal antibiotics within 60 minutes, before a source is identified, because morbidity and mortality rise with delay and many episodes are already bacteremic.

  • Complications

    Septic shock and multiorgan failure: the principal cause of death, driven by delayed antibiotics or inadequate source control.

  • Prognosis

    Outcome depends on treatment speed: prompt empiric antibiotics within 60 minutes and risk stratification are the strongest modifiable determinants of survival.

  • Prevention

    Primary or secondary prophylaxis with filgrastim 5 mcg/kg subcutaneously daily, started 24 to 72 hours after chemotherapy and continued until ANC recovery, for a high-risk regimen or any prior episode.

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