Summary:
A blinded prospective study was performed to determine whether screening of whole blood using a real-time, panfungal polymerase chain reaction (PCR) technique could predict the development of invasive fungal infection (IFI) in immunocompromised haemato-oncology patients. In all, 78 patients (125 treatment episodes) were screened twice weekly by real-time panfungal PCR using LightCyclerâ„¢ technology. IFI was documented in 19 treatment episodes (five proven, three probable and 11 possible), and in 12, PCR was sequentially positive. PCR positivity occurred in: 4/5 proven; 2/3 probable; 6/11 possible; and 29/106 with no IFI. In 8/12 with IFI and sequentially positive PCR results, PCR positivity occurred before (median 19.5 days) and in 4/12 (median 10.5 days) after the initiation of empirical antifungal therapy. Based on sequential positive results for proven/probable IFI sensitivity, specificity, positive predictive value and negative predictive value were 75, 70, 15 and 98%, respectively. Real-time panfungal PCR is a sensitive tool for the early diagnosis of IFI in immunocompromised haemato-oncology patients. It may be most useful as a screening method in high-risk patients, either to direct early pre-emptive antifungal therapy or to determine when empirical antifungal therapy can be withheld in patients with antibiotic--resistant neutropenic fever. However, these strategies require further assessment in comparative clinical trials.
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Acknowledgements
We are grateful to Dr M Leach, Dr B Hogg, Dr E Fitzsimons, Dr R Soutar, Dr N Lucie, Dr J Davies, Professor I Franklin and Dr G McQuaker for encouraging recruitment of patients to the study and to Dr P Donnelly for critical review of the manuscript. We also thank Dr L Mitchell and Ms C Nugent for consenting patients and collecting samples. We are indebted to Dr J Loeffler and Dr H Hebart at Tuebingen University for advice on establishing the PCR technique at our institution and to Dr E Ellis at Strathclyde University for providing technical support. Support for this work was provided by a grant from the Chief Scientists Office, Scotland. Educational grants (unrestricted) were provided by Wyeth Healthcare and Gilead Sciences.
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Jordanides, N., Allan, E., McLintock, L. et al. A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients. Bone Marrow Transplant 35, 389–395 (2005). https://doi.org/10.1038/sj.bmt.1704768
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DOI: https://doi.org/10.1038/sj.bmt.1704768
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