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Key Features

  • In patients with neutropenia, infection is a medical emergency

  • Fever

    • Defined as a single temperature of > 38.3°C (101°F) or a temperature of > 38°C (100.4°F) for > 1 hour

    • Although sometimes attributable to other causes, must be assumed to be due to an infection

  • The bacterial organisms accounting for the majority of infections in cancer patients include

    • Gram-positive bacteria (coagulase-negative Staphylococcus, Staphylococcus aureus, Streptococcus pneumoniae, Corynebacterium, and streptococci)

    • Gram-negative bacteria (Escherichia coli, Klebsiella, Pseudomonas, Enterobacter)

  • Gram-positive organism infections are more common but gram-negative infections are more serious and life-threatening

  • The risk of bacterial infections rises when the neutrophil count is < 500/mcL (0.5 × 109/L); the risk markedly increases when the count falls below 100/mcL (0.1 × 109/L) or when there is a prolonged duration of neutropenia, typically > 7 days

Clinical Findings

  • Fever (not always found in patients taking corticosteroids)

  • Shaking chills

  • Hypotension

  • Breathing difficulties

Diagnosis

  • Routine digital rectal examinations are generally avoided unless symptoms suggest a rectal abscess or prostatitis

  • If a rectal examination is necessary, antibiotics should be administered first

  • Appropriate cultures (eg, blood, sputum, urine, cerebrospinal fluid) should always be obtained

  • Two sets of blood cultures should be drawn before starting antibiotics

  • If the patient has an indwelling catheter, one of the cultures should be drawn from the line

  • Chest radiograph should also be obtained

Treatment

  • Initiate therapy immediately in the febrile, neutropenic patient

  • The choice of antibiotics depends on the patient's clinical status and any localizing source of infection

  • If the patient is clinically well despite the fever, monotherapy with an intravenous β-lactam with anti-Pseudomonas activity should be started

    • Cefepime

    • Ceftazidime

    • Imipenem/cilastatin

    • Piperacillin/tazobactam

  • If the patient is clinically ill with hypotension or hypoxia in addition to the fever, an intravenous aminoglycoside or fluoroquinolone should be added

  • If there is a strong suspicion of a gram-positive organism, such as from S aureus catheter infection, vancomycin can be given

  • The Infectious Disease Society of America (IDSA) has published recommendations for oral antibiotic use in low-risk febrile patients with neutropenia

    • Patients must have an expected neutropenic timeframe of 7 days or less

    • Patients must not have comorbidities or signs of

      • Hemodynamic instability

      • Gastrointestinal dysfunction

      • Altered mental status

      • Pulmonary problems (infiltrate, hypoxia, or underlying chronic obstructive pulmonary disease)

      • Liver or kidney disease or impairment

    • Antibiotics should be continued until the neutrophil count is rising and > 500/mcL (> 0.5 × 109/L) for at least 1 day and the patient has been afebrile for 2 days

    • For the neutropenic patient who is persistently febrile despite broad-spectrum antibiotics, an antifungal drug should be added (amphotericin B, caspofungin, itraconazole, voriconazole, or liposomal amphotericin B)

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