Antimicrobial Stewardship (AMS)

• Blood cultures
  • Fever, chills or rigors not associated with blood product infusion, draw aerobic and anaerobic blood cultures as follows:
    • 2 sets of blood cultures from separate venipunctures should be sent if no central venous catheter (CVC) is present
    • If CVC present, collect one set from central line AND one set from a peripheral vein
      • If peripheral specimen cannot be drawn, collect 2 sets from 2 different lumens of CVC
  • Blood cultures may be repeated in 48 to 72 hours if fever persists despite empiric antibiotic therapy. Otherwise, further blood cultures are not needed unless there is a worsening in clinical status.
• Microbiological testing from other sites of suspected infection should be obtained as clinically indicated, examples include:
  • Urine culture
  • If respiratory symptoms are present:
    • Sputum for bacterial and Legionella culture if productive cough
    • NP swab for COVID-19, influenza, RSV, and Extended respiratory panel (MRVP)
    • Legionella urinary antigen
  • C. difficile stool sample if diarrhea present
  • Note: many people have oropharyngeal colonization with Candida. Oropharyngeal candidiasis (thrush) is a clinical diagnosis. Swabs are rarely indicated but may be done if uncertainty of diagnosis or if refractory to nystatin or fluconazole.
• Chest radiograph (CXR)
  • A chest CT should be done if persistent fever of unclear cause, unexplained respiratory symptoms, or abnormal CXR requiring diagnostic clarification

Last reviewed July 2025

• Consider recent culture results and antimicrobial history when selecting empiric therapy.
• Administer antimicrobials as soon as possible (ideally after blood cultures collected) and within 1 hour of presentation if septic

FIRST LINE THERAPY:

• Piperacillin-tazobactam* 4.5 g IV q6h

*requires renal dose adjustment

• Consider the ADDITION of the following antimicrobials to empiric first line therapy in the following situations:
  • Azithromycin 500 mg PO/IV q24h:
    • suspected community acquired pneumonia
  • Vancomycin:
    • Septic shock OR
    • Prior colonization or infection with MRSA OR
    • Suspected catheter-related infection (chills/rigors with infusion through catheter or cellulitis around catheter exit site) OR
    • Skin and soft-tissue infection
  • Tobramycin:
    • Additional Gram-negative bacteria coverage in patients with signs of septic shock (while awaiting culture results) AND
      • Recent history (past 90 days) of receiving broad-spectrum antimicrobials (i.e. piperacillin-tazobactam or carbapenem)
      • OR
      • Recent infection/history of colonization with multidrug resistant Gram-negative bacteria

• Antifungal (e.g. fluconazole, caspofungin, voriconazole) not recommended in early undifferentiated febrile neutropenia

Last reviewed July 2025

Re-evaluate initial empiric antimicrobial therapy within 48-72 hours for escalation or de-escalation based on clinical status and microbiological data.

ESCALATION:

• Consider intensification of antimicrobial therapy for a deteriorating patient with worsening clinical status despite 48 hours of empiric therapy and no obvious cause
  • Fever alone is not a criterion to automatically escalate therapy, and requires reassessment and work-up

• Carefully assess for the source of infection including fungal, viral, and bacterial causes:
  • Repeat blood cultures
  • Urine culture
  • If respiratory symptoms are present:
    • Sputum for bacterial and Legionella culture if productive cough
    • NP swab for COVID-19, influenza, RSV, and Extended respiratory panel (MRVP)
    • Consider Legionella urinary antigen if not yet done
    • Imaging
      • A chest CT should be done if persistent fever of unclear cause, unexplained respiratory symptoms, or abnormal CXR requiring diagnostic clarification
    • Early bronchoscopy if unexplained pulmonary symptoms / CT findings to assess for mold infections including Aspergillosis, Mucor, and Pneumocystis pneumonia
  • Abdominal CT if concern of neutropenic enterocolitis, hepatosplenic candidiasis abdominal/pelvic/ischiorectal abscess
  • C. difficile stool sample if diarrhea present
  • Assess skin, mouth, and IV sites for lesions and infection
  • Non-infectious causes of fever should be considered such as drug reaction, blood product reaction, cancer mediated fever, thrombosis, graft-versus-host disease

ESCALATION OF ANTIMICROBIAL THERAPY

• Add tobramycin for additional Gram-negative bacterial coverage if the patient has signs of septic shock while awaiting culture results AND
  • Recent history (past 90 days) of receiving broad-spectrum antimicrobials (i.e. piperacillin-tazobactam or carbapenem) OR
  • Recent infection/history of colonization with multidrug resistant Gram-negative bacteria OR
  • Gram-negative bacilli or Pseudomonas in aerobic culture vials pending susceptibilities.

• Add vancomycin if:
  • Gram-positive cocci in blood culture Gram stain pending identification OR
  • Septic shock OR
  • Prior colonization or infection with MRSA OR
  • Suspected catheter-related infection (chills/rigors with infusion through catheter or cellulitis around catheter exit site) OR
  • Skin and soft-tissue infection

• Add antifungal coverage with caspofungin if:
  • Septic shock while receiving broad spectrum empiric antibiotics OR
  • Ongoing neutropenia and persistent fever of unknown cause for 5 days or more

Last reviewed July 2025

Re-evaluate initial empiric antimicrobial therapy within 48-72 hours for escalation or de-escalation based on clinical status and microbiological data.

DE-ESCALATION

Consider de-escalating the initial empiric antimicrobial regimen in the following situations:

• Infectious cause of fever is identified:
  • Microbiologically defined infection:
    • After 72 hours of empiric therapy: treat according to the clinical syndrome and susceptibility results with a narrow spectrum antimicrobial targeting the identified pathogen(s) if the patient is stable and afebrile.
    • S. aureus and Candida bloodstream infections require ID consultation and 14 days minimum of therapy from negative blood cultures.
  • Clinically documented infection:
    • If no pathogen is isolated but a focus of infection is identified, such as cellulitis or pneumonia, treat according to the syndrome.
  • Generally, antimicrobials are continued until all clinical signs of infection are resolved: 7-14 days for most syndromes

• De-escalation to appropriate oral therapy can be considered on a case-by-case basis.

• Unexplained fever (Infectious cause of fever is not identified):
  • Microbiology results are often negative, and patients usually improve with empiric therapy. In such cases, antimicrobials can be narrowed or discontinued as outlined below:
    • If vancomycin was started, it should be stopped after 48-72 hours if there is no indication such as MRSA, E. faecium, or CoNS infection
    • If tobramycin was started, it should be stopped after 48-72 hours if there is no indication such as a multidrug resistant Gram-negative infection
  • Stop ALL antimicrobials REGARDLESS of ANC recovery after 3-5 days if ALL of the following criteria are met:
    • patient is not a stem cell recipient AND
    • afebrile for at least 48hrs AND
    • negative blood cultures after 72h incubation AND
    • no severe mucositis AND
    • no localizing signs or symptoms of infection AND
    • no septic shock at onset
      • RCT of patients with hematological malignancies and profound neutropenia showed less antibiotic use and no safety issues compared with continuing antibiotics until ANC above 500 cells/microL
      • Supported by the 2011 4th European Conference on Infections in Leukemia and multiple observational trials^1,2,5
  • If fever recurs, perform cultures and restart empiric antimicrobials

Last reviewed July 2025

Last reviewed July 2025

Last reviewed July 2025