Anti-fungal policy (hamatology/oncology)

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Objectives

This guideline has been written to assist specialists in the prophylaxis and management of invasive fungal infection in children being treated for haematological malignancies. 

Scope

This guideline should be used by specialists caring for children with haematological malignancies and at risk of invasive fungal infections. 

1. Introduction

Invasive fungal infections (IFI) are an important cause of morbidity and mortality in patients with haematological malignancies, in particular those with prolonged and severe neutropenia. Treatment of invasive fungal infection with antifungal medicines is complicated in haemato-oncology patients due to the need for other potentially nephrotoxic or hepatotoxic medicines e.g. aminoglycosides, ciclosporin, tacrolimus and concomitant or potential nephrotoxic/hepatotoxic chemotherapy regimens.

2. Related resources

See the 'related guidelines' section at the bottom of this guideline

3. Authorised personnel/specific staff competencies

3.1 The diagnosis and management of fungal disease will be directed by the Consultant/Associate Specialist or a senior member of the medical team.

3.2 The Medical/Nursing team will be responsible for monitoring & investigation.

4. Equipment/materials

4.1 Blood culture bottles

4.2 Bacteriology swabs

4.3 Universal container

4.4 Stool sample container

5. Procedure

5.1 High Risk Group:

Patients with the following risk factors are at high risk of developing IFI:

  • Acute leukaemia
  • Neutrophil count of <0.5 x 10^9 /L for more than 2 weeks
  • Patients receiving high steroids
  • Recipients of allogeneic haematopoietic stem cell transplants
  • GvHD • Treatment with Fludarabine
  • Treatment with Campath
  • Previous fungal infection
  • Fluconazole resistant colonisation
  • Colonisation of more than one site plus neutropenia (neutrophils <1.0 x 109 /L)
  • Total body irradiation autograft

 

5.2 Diagnosis:

It is imperative that patients are regularly assessed for clinical features of IFI i.e:

  • Daily physical examination
  • Weekly bacterial screen including fungal screen(all patients who are neutropenic-neutrophils <1.0 x 109 /L)
    • Throat swab
    • Urine culture
    • Stool enteric pathogens
    • Central line swab
  • Early radiological imaging following persistent pyrexia for more than 72-96 hours i.e. preferably before, but definitely within 48-72 hours of commencing antifungal therapy.
  • In the first instance ultrasound of the liver and spleen. Consider early CT scanning of chest/sinuses if high suspicion. EORTC (European Organization for Research and Treatment of Cancer) criteria are helpful in determining the likelihood of proven/probable IFI

 

5.3 Monitoring of Renal Function:

Many antifungal medicines are nephrotoxic or hepatotoxic. Monitor serum creatinine daily and LFTs regularly during treatment.

 

5.4 Prophylaxis:

All haemopoietic stem cell transplant (HSCT) patients are commenced on IV Ambisome on the day of admission. It is prescribed on Mondays, Wednesdays and Fridays (dose: 2mg/kg/day).

When engraftment is established and there are no signs of IFI Ambisome will be substituted with oral itraconazole or posaconazole. Discuss with HSCT consultant or HSCT associate specialist prior to commencing anti-fungal prophylaxis. For doses see YBMT-CLIN-006 SOP.

If not tolerating oral medicines or high risk for IFI:

  • Ambisome 1mg/kg/day or 2mg/kg/day on Mondays, Wednesdays and Fridays.

If documented allergy to Ambisome:

  • Caspofungin 50mg/m2 on alternate days

 

5.5 Empirical/Possible IFI Therapy:

Patients eligible for empirical therapy should either:

  • Be in a high risk group with a pyrexia unresponsive to broad spectrum antibiotics for more than 96 hours

or

  • fulfill the EORTC Criteria for Possible IFI
POSSIBLE INVASIVE INFECTION
At least 1 host criterion
AND
EITHER 1 microbiological criterion
OR 1 major OR 2 minor clinical criteria

Ambisome 3mg/kg/day (doses can be increased to 10mg/kg/day) in proven infections.

If allergic to Ambisome or impaired renal function:

Caspofungin: 70mg/m2 on D1, then 50mg/m2 once daily

 

5.6 Proven/Probable IFI Therapy:

PROBABLE INVASIVE INFECTION
At least 1 host criterion
AND 1 microbiological criterion
AND 1 major OR 2 minor clinical criteria


Treatment drugs and doses as for empirical therapy (see section 5.5)

Voriconazole (by intravenous infusion):

  • Child 2-12 yrs (and child 12-15 years if body weight under 50 kg): 9mg/kg every 12 hours for 2 doses then 8mg/kg every 12 hours (reduced in steps of 1m/kg if not tolerated; increased in steps of 1mg/kg if inadequate response) for maximum 6 months.
  • Child 15- 18 years (body weight over 50kg): 6mg/kg every 12 hours for 2 doses then 4mg/kg every 12 (reduced to 3mg/kg if not tolerated) for maximum 6 months.

N.B: For individuals with evidence of intracerebral infection intravenous voriconazole is the drug of choice due to excellent penetration of the blood brain barrier

 

5.7 Alternative Agents:

Posaconazole can be used to treat invasive aspergillosis which is unresponsive to Ambisome, or in patients intolerant to Ambisome, voriconazole or fluconazole (see YMBT-CLIN-0006 SOP for dosing and side-effects).

 

5.8 Additional Agents:

The addition of the following agents to antifungal therapy can be considered depending on the patients’ clinical condition.

G-CSF - Lenograstim 5mcg/kg equivalent dose, can be doubled to 10mcg/kg equivalent dose if required.

6. Audit & review process

6.1 This SOP will be reviewed every two years.

6.2 Identify how the procedure/process within the SOP will be audited

7. Further information/exceptions

For further information contact:

Haemopoietic Stem Cell Transplant Team

Ext: 81880 / 81879 / 89304

References
Editorial Information

Last reviewed: 01 March 2015

Next review: 01 March 2017

Author(s): Dr A M Ewins

Approved By: Clinical Effectiveness