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Fungal Infections in the oncology patient

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Shared care information

Patients with suspected fungal infection should be discussed with the paediatric oncologist on call as they will usually need treatment in an oncology unit.

Risk factors

The two most commonly diagnosed fungal infections are candidiasis and aspergillosis. Patients most at risk of systemic fungal infection are those with prolonged severe neutropenia on broad-spectrum antibiotics.

Clinical features

These depend on the site of infection.

  • Fever (this may be the only clinical sign)
  • Cough, hypoxia
  • Sinus pain and/or discharge which may be clear or purulent
  • CNS signs (fungal space occupying lesion)
  • Hepatic transaminitis and/or abdominal pain
  • Renal dysfunction (renal fungal balls)

Patient risk stratification

Low risk

PBSC autologous transplant
Childhood ALL 

Intermediate risk

Low Neuts 0.1-0.5 x 109/L for <3 weeks; lymphs <0.5 x 109/L on AB e.g., cotrimoxazole
CVC 
High     Colonised at >1 site or heavily at 1 site, neuts 0.1-0.5 x 109/L for 3-5 weeks 
AML
TBI 
Allogeneic matched sibling SCT 
Very High         Neuts <0.1 x 109/L for >3 weeks 
Colonised by candida tropicalis 
Allogeneic MUD or mis-matched SCT 
GVHD 
Neuts < 0.5 x 109/L for >5 weeks 
Pred >1 mg/kg (or equivalent) and neuts <1 x 109/L for >1 week 
Pred >2 mg/kg (or equivalent) for >2 weeks 
High dose cytarabine (Ara-C) 
Fludarabine (uncertain) 

Investigations

This is generally done during investigations for persistent or recurrent PUO while on broad spectrum Abs:

  • CT scan - high resolution chest looking for specific (halo sign) or non specific (pneumonitis, nodules) features.
  • CT scan - head, sinuses, abdomen (hepatosplenic lesions) and pelvis.
  • Biopsies - if the patient is relatively well and BAL/biopsy (open or CT guided) can be arranged rapidly it is ideal to do this before starting antifungal therapy.
  • Non-culture based rapid diagnostic tests. There is some evidence for using Galactomannan as a screening test with reasonable specificity in adults. This section will be updated when there is further experience with these tests.

Aspergillus Species

Aspergillus is the most common mould causing invasive fungal infections. It is inherently resistant to fluconazole. The risk of infection is markedly reduced (but not entirely avoided) by nursing high-risk patients in filtered, positive pressure air. Rates of infection are increased in units where there are building works nearby.

Clinical features

  • pulmonary infiltration (best seen on CT scan)
  • sinus infiltration
  • occasionally focal CNS signs.

Investigations

As above

Management

There is insufficient data from paediatric trials to guide treatment of invasive aspergillus. Extrapolation from adult trials suggests that voriconazole may be superior to conventional amphotericin B but there were differences in treatment durations between the 2 arms of this trial and there are no head to head studies with liposomal amphotericin.

Treatment options are:

  • Voriconazole 6 mg/kg/dose bd with liposomal amphotericin 3 mg/kg/dose which can be stopped when therapeutic voriconazole levels are achieved. Therapeutic drug monitoring is required as some children may require up to 12 mg/kg/dose bd to achieve therapeutic levels.
  • Liposomal amphotericin 3 mg/kg daily
  • Caspofungin 50 mg/m2 daily as a second line agent.

Candida Albicans and Other Candida Species

There are several different types of Candida which have different susceptibility patterns(1). Currently:

Patterns of susceptibility to licensed antifungal agents among the major Candida species (*).

- Amphotericin B Caspofungin Fluconazole Voriconazole
C. albicans S S S S
C. glabrata S S S-DD to R S to I
C. krusei S S R S to I
C. parapsilosis S S (**) S S
C. tropicalis S S S S

Table adapted from Ostrosky-Zeichner and Pappas, 2006.

(*) Patterns of susceptibility are based on results of > 75% of clinical isolates.

(**) Intermediate susceptibility is rarely reported.

Clinical Features

These are variable and include:

  • skin and/or mucosal infection
  • severe oesophagitis
  • hepato-splenic syndrome with fever, mild jaundice and raised liver enzymes, and increasing hepatomegaly and sometimes splenomegaly.
  • systemic disease with fever, jaundice and pulmonary infiltrates.

Management(1)(2)

Most of the trials in children have been done in predominantly non-neutropenic patients. There are no adequately powered studies in neutropenic children with invasive candida. There is no evidence that any one agent is more effective than another.

  • Previous therapy should be considered (prior use of fluconazole selects for fluconazole resistant organisms)
  • The antifungal used should be chosen depending on the candidal species isolated until sensitivities are available (if required)
  • Fluconazole (6 mg/kg PO or IV daily for non-invasive and superficial infection, and 12mg/kg IV or PO daily for invasive disease) remains the treatment of choice for proven candidal infection in non-neutropenic patients unless there is local epidemiological data suggesting high rates of resistant species.
  • In neutropenic patients with proven candida a fungicidal agent (an echinocandin or polyene) is suggested.
  • Caspofungin 70 mg/m2 loading for the first dose, followed by 50 mg/m2 daily
  • Ambisome 1-3 mg/kg/day

Therapy should continue for at least 14 days after the last positive culture, 4 weeks for meningitis and > 6 weeks for chronic disseminated candida, endocarditis, endopthalmitis and osteomyelitis(2).

Other Fungi

While candida and aspergillus species are the commonest fungi that cause invasive infections, outbreaks of other fungi are not uncommon.

  • Yeasts: Cryptococcus
  • Zygomycetes (black mould): Mucor, rhizomucor
  • Hyphomycetes: Fusarium, Scedosporium

Investigations

As for other fungi except for Cryptococcus. This requires samples from:

  • Urine
  • Blood
  • Sputum
  • CSF

As well as CT head

Management

Discuss all these cases with Infectious Diseases as soon as possible.

  • Cryptococcus
    Treatment with amphotercin is required but this should be discussed with oncology unit and infectious diseases.
  • Zygomycetes
    • Liposomal amphotericin 5 mg/kg/day (resistant to voriconazole but susceptible to posaconazole)
    • Aggressive surgical debridement
  • Scedosporium
  • Optimal treatment is unknown. Azoles are probably superior to polyenes (amphotericin) but some species are resistant to all antifungals
  • Fusarium
    Amphotericin, voriconazole or posaconazole may all be effective but sensitivities vary so susceptibility testing is recommended.

References

  1. Thursky et al. Recommendations for the treatment of established fungal infections. IMJ;2008;38(6b):496-520.
  2. Blyth CC, Palasanthiran P, O'Brien TA. Antifungal therapy in children with invasive fungal infections:a systematic review. Pediatric; 2007;119(4):772-784.References
  3. Slavin M, Introduction to the updated Australian and New Zealand consensus guidelines for the use of antifungal agents in the haematology/oncology setting, 2008. IMJ 2008;38:457-467

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Document Control

  • Date last published: 03 March 2014
  • Document type: Clinical Guideline
  • Services responsible: National Child Cancer Network