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High-Risk Febrile Neutropenia Guideline

Single oral temperature of 38.3°C or sustained oral temperature of ≥ 38.0°C for > 1 h
AND: ANC ≤ 0.5 x 109/L

Severe beta-lactam allergy

Clindamycin 600 mg IV q8h
AND: Tobramycin 7 mg/kg IV q24h
(order tobramycin peak level and random 8-12h level)

If pneumonia suspected:
Meropenem 500 mg IV q6h
(dose adjustment required in renal dysfunction)
AND: Azithromycin 500 mg po q24h

Consider Infectious Diseases referral for allergy assessment and testing

No allergy

Start Piperacillin/tazobactam 4.5 g IV q6h *
(dose adjustment required in renal dysfunction)

* Meropenem (500 mg IV q6h) may be used as an alternative in the setting of a suspected ESBL infection (known colonization with ESBLs) or septic shock

† Add azithromycin 500 mg po q24hif pneumonia suspected

Consider the addition of IV vancomycin* in the following situations:

  • Hemodynamic instability
  • Suspected catheter-related sepsis or Staphylococcus aureus bacteremia pending susceptibility
  • Colonization with MRSA

Consider the addition of tobramycin* in the following situations:

  • Hemodynamic instability
  • Suspected Pseudomonas sepsis pending susceptibilities to piperacillin-tazobactam

Suspected or documented C. difficile infection:

  • Add vancomycin 125 mg po QID

*NOTE: Re-assessment within 24-48 hours based on clinical status and culture results

Re-evaluate therapy on Day 3

If Afebrile x48 hours

No Infectious etiology identified

If initial fever thought to be leukemia-related, may consider discontinuing antimicrobial therapy

Otherwise: Consider oral therapy in patients who are clinically well

Options:

Cephalexin 500mg po QID
AND: Ciprofloxacin 750mg po BID*

OR

Amoxicillin/clavulanate 875/125mg po BID
AND: Ciprofloxacin 750mg po BID*

*dose adjustment required in renal dysfunction

Duration of therapy dependant on ANC

If ANC < 0.5, treat for 7-14 days based on clinician discretion

If ANC ≥ 0.5 if ANC ≥ 0.5 and patient afebrile for 2 days, consider discontinuing antibiotics

Infectious etiology identified

If ANC < 0.5:

Maintain broad-spectrum coverage while patient remains neutropenic (ANC < 0.5).

Once ANC > 0.5 x 2 consecutive days: Narrow antibiotic selection to target the specific diagnosed infection.

Route and total duration of therapy should be based on site/type of infection and clinical status of patient.


If ANC ≥ 0.5 x 2 consecutive days:

Narrow antibiotic selection to target the specific diagnosed infection.

Route and total duration of therapy should be based on site/type of infection and clinical status of patient.

If Persistent Fever

Patient is clinically unstable or demonstrating signs of clinical deterioration (e.g. evidence of poor perfusion –hypotension, oliguria, impaired consciousness)

Consider broadening antimicrobial therapy
Consult Infectious Diseases

Patient is clinically stable

An unexplained persistent fever in a patient whose condition is otherwise stable does not require an empirical change to the initial antibiotic regimen.

Continue empiric therapy
The need for adjunctive antibiotic therapies should be re-assessed based on culture results

Re-evaluate therapy on day 4-5

Afebrile x 48 hours 

Duration of therapy dependant on ANC

ANC < 0.5 (and no new infections identified):
Treat for 7-14 days based on clinician discretion in the absence of a documented infection that may require a longer duration.

May consider oral step down if patient is clinically well, but maintain broad-spectrum coverage while patient is neutropenic (ANC <0.5).

ANC ≥ 0.5:

If ANC ≥ 0.5 x 2 consecutive days and patient is afebrile x 2 days, may discontinue antibiotics in the absence of a documented infection that may require a longer duration.

Persistent Fever 

Consult Infectious Diseases

Empiric antifungal therapy is rarely required before day 7 of febrile neutropenia

*Visit the Renal adjustment page for more information.

SB Febrile Neutropenia Guideline 2019 (November 11, 2019) PDF 

Last updated: November 11, 2019

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