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Diagnostic versus empirical


Diagnostic-driven strategy versus empirical treatment: how to save costs?


In this chapter, invasive fungal infection treatment is investigated, with the factors of both lowering costs and reducing resistant organisms and toxicity in mind


Fiona Dignan MBChB MRCP FRCPath MD Consultant Haematologist, Manchester Royal Infirmary, UK


Invasive fungal infection (IFI) remains a concern in high-risk patients including those undergoing treatment for haematological malignancies with chemotherapeutic agents and stem cell transplantation. Historically, treatment has been empirical in nature based on the presence of recurrent or persistent fevers, but more recently pre-emptive or diagnostic-driven strategies have been investigated in an attempt to reduce the use of antifungal agents. These strategies have the potential to reduce the cost of antifungal therapy while also reducing the possibility of resistant organisms and toxicity. This chapter will review the investigations used in diagnostic-driven strategies and recent publications on how these may be adopted in clinical practice.


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Investigations used in diagnostic-driven strategies There are four main components of diagnostic-driven strategies including clinical features, microbiological investigations, biomarkers and radiological tests. Clinical features can include recurrent or persistent fevers and respiratory symptoms including cough, hypoxia, chest pain or sinusitis. Microbiological investigations may include conventional cultures of blood, sputum, broncho-alveolar lavage or tissue specimens. Histopathological assessment of tissue specimens may also play a role.


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“Diagnostic-driven strategies include clinical features, microbiological investigations, biomarkers and radiological tests“


Radiological investigations primarily include chest X-rays and computed tomography (CT) scans of the thorax. More recently, new biomarkers have been introduced including galactomannan, β-D-glucan and polymerase chain reaction (PCR) tests for aspergillus. All aspergillus species release a cell wall component called


galactomannan. An enzyme immunoassay may be used to detect this component in


serum, broncho-alveolar lavage fluid and cerebrospinal fluid. Galactomannan positivity has been included in the European Organisation for Research and Treatment of Cancer (EORTC) definitions of invasive fungal infections.1


The role of


PCR particularly in pre-emptive strategies remains investigative.2


β-D-glucan is a


cell wall component of a number of fungal species including candida and aspergillus that has been found to be more sensitive


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