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Neutropenic fever

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Febrile neutropaenia

  • Increased susceptibility to infection when neutrophil count <1 x 106 /L

  • Below that level frequency and severity inversely related to neutrophil count

Clinical features

  • Features of inflammation may be minimal or absent in the severely neutropaenic patient, especially if anaemic. Patient may have cutaneous infection without typical cellulites, pulmonary infection without CXR infiltrates, meningitis without CSF pleocytosis and UTI without pyuria

  • Commonest sites of infection:

    • Periodontium

    • Pharynx

    • Lower oesophagus

    • Lung

    • Perineum and anus

    • Fundus of the eye

    • Skin

    • Bone marrow aspiration sites

    • Vascular access sites

    • Periungual tissue


  • Selection of antibiotics should be tailored to local microbiological flora and antibiotic susceptibility patterns

  • Vascular access devices may be left in place even if local entry site infection or catheter related bloodstream infection is diagnosed under certain circumstances. The catheter should be removed for:

    • Recurrent infection

    • Lack of response to antibiotics within 2-3 days

    • Evidence of subcutaneous tunnel infection or periport infection

    • Septic emboli

    • Hypotension associated with catheter use

    • Non patent catheter

    • Atypical mycobacterium infection (removal should be combined with generous debridement of infected tissue)

    • Bacillus species, P. aeruginosa, Stenotrophomonas maltophilia, C. jeikeium, vancomycin resistant enterococcus, Candida, Acinetobacter catheter related bloodstream infection

  • No marked difference in efficacy between monotherapy and dual therapy for uncomplicated episodes of neutropaenic fever although dual therapy has potential benefits of synergistic effects against some Gm –ves and minimal emergence of resistant organisms during therapy. A recent meta-analysis demonstrated a lower incidence of treatment failure and adverse effects in patients treated with a broad-spectrum beta-lactam compared with a beta-lactam plus aminoglycoside. There was no statistically significant difference in survival.

  • Quinolone plus beta-lactam or glycopeptide is an option for initial therapy in patients who have not received prophylaxis with quinolones

  • In general it is desirable to continue antibiotics until neutrophil count ³0.5 106 /L but if neutropaenia is prolonged, the patient has received at least 7 days of treatment, the causative organism has been eradicated and there are no clinical features of infection then it may be reasonable to stop treatment before this target is reached

  • Fever for >3 days, infected site, no organism identified, consider:

    • Non-bacterial infection

    • Bacterial infection

      • Resistant to antibiotics

      • Slow to respond to antibiotics

      • Inadequate serum or tissue concentrations of antibiotic

      • Avascular site (eg abscess or catheter)

      • Cell wall-deficient bacteria

      • Second infection

    •   Drug fever

  • Use and timing of antifungal therapy controversial but most clinicians believe that patients who remain febrile and profoundly neutropaenic for ³5 days despite adequate doses of broad spectrum antibiotics should be given antifungal therapy. However, if the neutrophil count is expected to recover in a few days, fungi have not been isolated from any site and the patient is not profoundly unwell then it may be appropriate to withhold antifungal therapy.

  • Antifungal therapy usually consists of amphotericin B but fluconazole is an acceptable alternative in institutions in which mold infections (eg Aspergillus) and fluconazole resistant Candida species (Candida krusei and some Candida glabrata) are uncommon. Click here for more details

Duration of therapy

  • Patients who are afebrile within 3-5 days but remain profoundly neutropaenic (<0.1 x 106/L), have mucous membrane lesions of mouth or GI tract or unstable vital signs: consider admininstration of antibiotics throughout the neutropaenic period

  • Patients who remain febrile after recovery of neutrophil count to >0.5 x 106/L despite broad spectrum antibacterial therapy:

    • Reassess patient with particular attention to fungal, mycobacterial or viral infections

    • Antibiotic therapy can generally be stopped despite fever 4-5 days after neutrophil count exceeds 0.5 x 106/L if no infectious lesions are detected

  • Patients who remain febrile and whose neutrophil count remains <0.5 x 106/L

    • Continue antibiotics for 2 weeks. Reassess. If no site of infection has been identified stop antibiotics and monitor carefully.

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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