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Febrile Neutropenia

  • Notes

    • Infection is a significant cause of morbidity and mortality in oncology patients.
    • Febrile neutropenia in an oncology patient may be the only indication of severe infection, because symptoms and signs of inflammation are typically attenuated.
    • Fever is defined as a single tympanic temperature >= 38.5°C or a sustained temperature >= 38.0°C over 1 hour.
    • Neutropenia is defined as an absolute neutrophil count < 500/mm3 OR < 1000/mm3 with predicted decline to < 500/mm3 over the next 48 hours.
    • In general, febrile neutropenia is an indication for commencing empiric antibiotics after taking appropriate cultures. Severe infection may also occur in the absence of fever or neutropenia in oncology patients.
    • The administration of antibiotics should not be delayed.  If the antibiotics recommended in this guideline are unavailable, a combination of aminoglycoside plus beta-lactam antibiotic should be used. The combination of timentin (ticarcillin/clavulanate) AND gentamicin remains appropriate for treatment of febrile neutropenia in many hospitals.

    Clinical assessment

    Full history with particular attention to:

    • New symptoms
    • Infection exposures
    • Type of cancer, phase of cancer treatment (ie. ALL in induction) and most recent chemotherapy

    Full examination with particular attention to:

    • Cardiovascular status for signs of dehydration or sepsis
    • Upper respiratory tract for otitis media and sinusitis
    • Oropharynx for dental abscess and mucositis
    • Lower respiratory tract for signs suggestive of Pneumocystis jiroveci (PCP) pneumonia (cough, tachypnoea, hypoxia, interstitial infiltrate on CXR)
    • Abdomen for signs of Clostridium difficle colitis (generalised abdominal tenderness) or typhlitis (tenderness over caecum)
    • Skin for cellulitis or vesicular lesions
    • Perineum and perianal area for anal fissure, cellulitis or abscess
    • Central venous access device (CVAD) for signs of tunnel/exit site infection
    • Signs of anaemia and/or thrombocytopenia

    Investigations:

    Always:

    If indicated:

    Respiratory symptoms:

    • CXR (there may be no changes while neutropenic)
    • NPA, or throat swab if thrombocytopenic, for viral PCR (only if requested by Oncology team after review. Patient placement should NOT be delayed whilst waiting for results) - link to NPA guideline 
    • Sputum for M/C/S in older children

    Diarrhoea:

    • Stool for M/C/S and viral studies
    • Stool for C. difficile toxin assay if recent treatment with antibiotics

    Skin, CVAD site or mouth lesions:

    • Bacterial swab for M/C/S (including Gram stain slide)
    • Viral swab of vesicular lesions and mouth ulcers for viral PCR

    CNS symptoms

    • CT brain and lumbar puncture may be indicated if there are new CNS symptoms or signs. Please discuss with on call Oncologist first.
    • Correction of thrombocytopenia and/or coagulopathy must occur prior to LP.

    Other

    • Cross-match

    Management

    General

    • All febrile oncology patients must be discussed with the Emergency Fellow/Consultant and the Oncology Fellow/Consultant on call.
    • Do not delay antibiotics while waiting for results of laboratory investigations unless advised by the consultant.
    • Arrange urgent admission to the appropriate ward. Patients on high risk treatment protocols should ideally be admitted to 6th floor.
    • Patients with low grade fevers or higher neutrophil counts, who have evidence of viral infection or a clear localised infection, such as otitis media, may be observed carefully or treated with an appropriate oral antibiotic. They should be reviewed by the Oncology team within 24 hr. Patients with persistent fevers may require i.v. antibiotics.
    • Never administer PR medications

    Vascular access

    Central venous access devices, if present, should be accessed by appropriately trained nursing staff from Emergency Department for blood sampling and administration of antibiotics. Please contact the 6th Floor Nurse Unit Manager if assistance is required.

    Initial antibiotics

    Patients admitted to RCH

    For antibiotic doses, refer to table below.

    Patients with double lumen CVAD should have antibiotics divided and administered down both lumens.

    Patients admitted to hospitals other than RCH

    • The choice of empiric antibiotics for febrile neutropenia should be based on local antibiotic susceptibility data.
    • Patients who receive cancer treatment at RCH should be managed according to RCH febrile neutropenia guidelines.
    • Other patients may be managed according to either RCH or to local febrile neutropenia guidelines. This may include monotherapy with an anti-pseudomonal beta-lactam antibiotic or combination therapy with an aminoglycoside plus beta-lactam antibiotic. The combination of timentin (ticarcillin/clavulanate) AND gentamicin remains appropriate for treatment of febrile neutropenia in many hospitals.

    Indications for Vancomycin

    • Proven Gram positive bacteraemia (vancomycin should be ceased if susceptibilities indicate an alternative agent can be used)
    • Severe sepsis
    • Known MRSA colonisation
    • Suspected catheter related infection including
      • Onset of fever and/or sepsis directly related to CVAD access
      • Exit site or tunnel infection

    Prolonged fever in a clinically stable patient is NOT an indication to commence vancomycin.

    Specific therapy

    • Initial empiric antibiotics may need adjusting depending on clinical assessment and culture results
    • Please discuss all changes to empiric therapy with oncology consultant on call

    Antibiotic table

    Antibiotic1  Dose Troughtarget 
    (dose adjustment may be required)
    Amikacin  22.5 (18 if >10y) mg/kg (max 1.5 g) iv 24H< 2 mg/L (pre 3rd dose)
    Gentamicin  7.5 (6 if >10y) mg/kg (max 360 mg) iv 24H 
     < 1 mg/L (pre 3rd dose)
    Piperacillin-tazobactam2 100 mg/kg (max 4 g) iv 6H  Not applicable
    Ticarcillin-clavulanate3 (Timentin®) 50 mg/kg (max 3 g) iv 6H
     Not applicable
    Vancomycin15 mg/kg (max 500 mg) iv 6H 
    10-15 mg/L (pre 5th dose)
    (15-20 mg/L may be indicated for complicated infections)
    1. IV aminoglycoside antibiotics (gentamicin and amikacin) should not be given simultaneously through the same line as IV penicillins including piperacillin-tazobactam and ticarcillin-clavulanate. The line should be flushed well with sodium chloride 0.9%, before and after giving each medication.
    2. Trade names for piperacillin-tazobactam include Tazocin®, Tazopip®, PiperTaz®, and DBL Piperacillin and Tazobactam®. Doses refer to piperacillin component.
    3. Doses refer to ticarcillin component.

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