Alessandro C Pasqualotto Post-doctoral Reseacrh Associate, and Senior Lecturer in Medicine and Medical Mycology, University of Manchester , David W Denning Post-doctoral Reseacrh Associate, and Senior Lecturer in Medicine and Medical Mycology, University of Manchester

Originally printed in:
» European Oncology Review 2005 - July 2005

Despite the availability of new antifungal drugs, the overall survival for immunocompromised patients with invasive fungal infections remains too low, with large variations according to underlying disease.^1–15 Although early diagnosis and subsequent early initiation of therapy improves outcome,^16–19 diagnosing invasive fungal infections can be difficult. The purpose of this article is to review the available armamentaria for the diagnosis of invasive fungal infections. A brief summary of the main clinical and epidemiological data for these infections is shown in Table ^{1.3–7,12–15,20–56}
Diagnosis of Invasive Fungal Infection

Conventional Methods (Direct Microscopy, Culture and Histopathology)

All fungi obtained from sterile sites should be identified to species level by referral to a specialist laboratory. All bronchoscopy fluids from patients suspected of infection should be examined microscopically for hyphae and cultured on specialised media, and all clinical isolates of Aspergillus should be identified to species level.57

Current ‘conventional methods’ are very limited for the diagnosis of invasive fungal infections. Blood cultures have a low sensitivity for the diagnosis of candidaemia (~50%),^58,59 and cultures other than blood are non-specific and can take too long to became positive. Antifungal treatment is recommended following recovery of even one positive blood culture for Candida.⁵ Identification of Candida spp. by culture requires the presence of viable organisms in blood or body fluids. In addition, several days may be required for blood cultures to become positive and, for non-Albicans spp. of Candida, additional subculturing is required to obtain pure cultures for use in subsequent phenotypic identification systems.⁵⁹

Although the lungs are frequently involved in disseminated candosis, primary Candida pneumonia is a rare condition,^60,61 and benign colonisation of the airway with Candida spp. and/or contamination of the respiratory secretions with oropharyngeal material is much more common than true Candida pneumonia. Thus, diagnoses of Candida pneumonia that are based solely on microbiological data are often incorrect. In addition, debate persists about the significance of the isolation of Candida in the peritoneal fluid,⁶² and the presence of Candida in the urine usually represents colonisation, despite its presence in 9% of hospitalised patients in the US.⁶³

For the diagnosis of invasive aspergillosis, cultures of the respiratory tract secretions lack sensitivity. Aspergillus is grown from sputum in only 8% to 34%, and from broncho-alveolar lavage (BAL) in 45% to 62% of patients with invasive aspergillosis.64 Aspergillus recovery from the respiratory tract usually represents colonisation in immunocompetent patients but may strongly suggest invasive disease in the immunocompromised host.^65,66 While confirmation of the diagnosis of invasive aspergillosis has typically required histopathologic evaluation, profound neutropaenia and thrombocytopaenia often preclude the pursuit of biopsies. Transbronchial biopsy or brushings are too often false negative. Biopsies of endobronchial lesions have been useful when such lesions are encountered. Blood, cerebrospinal fluid (CSF) and bone marrow specimens rarely yield Aspergillus spp.³³

In contrast to disseminated aspergillosis, disseminated fusariosis can be diagnosed by blood cultures in 40% of patients.^12,15 The rate of positive blood cultures increases to 60% in the presence of disseminated skin lesions.¹⁴ Microscopically, the hyphae of Fusarium in tissue resemble those of Aspergillus; the filaments are hyaline, septate and 3–8µm in diameter. They typically branch at acute or right angles. The production of both fusoid macroconidia and microconidia are characteristic of the genus Fusarium.¹³ Skin lesions should be submitted to biopsy.