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Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients : a randomised controlled trial . BACKGROUND Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis . We compared a standard diagnostic strategy ( culture and histology ) with a rapid biomarker-based diagnostic strategy ( aspergillus galactomannan and PCR ) for directing the use of antifungal treatment in this group of patients . METHODS In this open-label , parallel-group , randomised controlled trial , eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia , with no history of invasive fungal disease . Enrolled patients were randomly assigned ( 1:1 ) by a computer-generated schedule to follow either a standard diagnostic strategy ( based on culture and histology ) or a biomarker-based diagnostic strategy ( aspergillus galactomannan and PCR ) to direct treatment with antifungal drugs . Patients , were followed up for 26 weeks or until death . Masking of the use of different diagnostic tests was not possible for patients , treating physicians , or investigators . The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment ( for the biomarker-based diagnostic strategy , a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis , so treatment in this context was classified as empirical ) . This outcome was assessed by an independent data review committee from which the study allocations were masked . Analyses were by intention to treat and included all enrolled patients . This study is registered with ClinicalTrial.gov , number NCT00163722 . FINDINGS 240 eligible patients were recruited from six Australian centres between Sept 30 , 2005 , and Nov 19 , 2009 . 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy . 39 patients ( 32 % ) in the standard diagnosis group and 18 ( 15 % ) in the biomarker diagnosis group received empirical antifungal treatment ( difference 17 % , 95 % CI 4-26 ; p=0·002 ) . The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups ( hepatotoxic effects : 21 [ 17 % ] vs 12 [ 10 % ] , p=0·11 ; nephrotoxic effects : 52 [ 43 % ] vs 60 [ 51 % ] , p=0·20 ) . INTERPRETATION Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment . This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients . FUNDING Australian National Health and Medical Research Council , Cancer Council New South Wales , Pfizer , Merck , Gilead Sciences .
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Intervention_Pharmacological
Galactomannan
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Intervention_Pharmacological
PCR
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Intervention_Pharmacological
chemotherapy
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Intervention_Psychological
standard diagnostic strategy
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Intervention_Pharmacological
biomarker-based diagnostic strategy
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Intervention_Physical
(
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Intervention_Pharmacological
aspergillus galactomannan
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Intervention_Physical
and
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Intervention_Pharmacological
PCR
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Intervention_Physical
)
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Outcome_Other
empirical treatment
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Outcome_Physical
with
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Outcome_Other
antifungal drugs