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Emergencies >> Neutropenic fever

(Leukocytes <1000/ul or neutrophils <500/ul)

Background:

Leukopenia, especially neutropenia increases the risk of bacterial or fungal infections. There are 3 risk groups:

Low riskEstimated duration of neutropenia up to 5 days (e. g. for CHOP)
Intermediate riskEstimated duration of neutropenia up to 6-9 days (e. g. for Ifosfamide/doxorubicin)
High riskEstimated duration of neutropenia over 10 days (all induction/consolidation therapies for leukemia and high-dose chemotherapies)

Symptoms:

Fever over 38°C, chills, pallor or greyness of skin, fatigue

Diagnostics in case of initial fever:

Obligatory

  • Physical examination (infectious focus)
  • Complete laboratory work-up with CRP (ev. procalcitonin), lactate and alkaline phosphatase
  • Blood culture (aerob, anaerob), from 2 different locations, e. g. from central venous line and from arm BEFORE start of antibiotics
  • Chest-X-ray
  • Ultrasound of abdomen
  • Urine analysis, stool sample (incl. Clostridium difficile in case of diarrhea)
  • Daily laboratory with CRP and physical examination

Optional or in case of symptoms

  • Samples from wounds or other lesions
  • Echocardiography
  • Removal of central venous line (if erythema, tenderness)
  • Aspergillus antigen
  • Bronchoalveolar lavage in case of suspected invasive fungal infection, PCP, tuberculosis or others
  • Spinal tap in case of neurologic symptoms

Diagnostics in case of persistent fever (despite antibiotics) after 72 hours:

  • Repeat blood cultures
  • High-resolution computed tomography of the thorax for the exclusion of an invasive fungal infection
  • Sonography or CT of the liver and alkaline phosphatase in case of suspected invasive fungal infection of spleen and liver.

Therapy:

  • The therapy has to be started immediately!
  • Fluids (if renal function is not impaired >2 l / day)
  • Antibiotics can be discontinued after 3 non-neutropenic fever-free days or after 7 neutropenic fever-free days.

Low risk

  • Quinolone orally (mono or) in combination with amoxicillin/clavulanic acid
  • In case of risk factors (low PS, concomittant disorders, old age, sepsis, shock, compliance problems), the patient should be admitted for closer monitoring!

Intermediate risk

Combination therapy: cephalosporin of class 3 or 4 + aminoglycoside (e. g. ceftriaxon 2 g/d + gentamicine 5 mg/kg – CAVE creatinine) OR acylaminopenicillin + aminoglycoside

Monotherapy: piperacillin/tazobactam OR ceftazidim OR cefepime OR imipenem/cilastatin OR meropenem

If the patient worsens under therapy, the antibiotics must be switched.

After 72 hours of persistent fever: infectious diseases consult, diagnostics (as described above) and change of therapy plus antifungal systemic treatment. If bacteria are found in the blood culture, consider checking sensitivities.

Fever after further 72 hours: Possible escalation with a glycopeptide (vancomycin, teicoplanin)

High risk

Combination therapy: cephalosporin of class 3 or 4 + aminoglycoside (e. g. ceftriaxon 2 g/d + gentamicine 5 mg/kg – CAVE creatinine) OR acylaminopenicillin + aminoglycoside

Monotherapy: piperacillin/tazobactam OR ceftazidim OR cefepime OR imipenem/cilastatin OR meropenem

If the patient worsens under therapy, the antibiotics have to be switched.

After 72 hours of persistent fever: infectious diseases consult, diagnostics (as described above) and change of therapy plus antifungal systemic treatment. If bacteria are found in the blood culture, consider checking sensitivies.

Fever after further 72 hours: Possible escalation with a glycopeptide (vancomycin, teicoplanin)

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