Spiralling empiricism



Clinical studies on antifungal treatment (AFT) in immunocompromised hosts are hampered by the lack of standardized case definitions, the difficulty to establish the proof of an invasive fungal infection (IFI) ante mortem, and the heterogeneity of criteria used for response assessment. Since AFT must be started as early as possible in order to improve prognosis, and isolation of pathogenic fungi from otherwise sterile body sites may indicate an already far advanced IFI, trials showing favorable results of AFT frequently are based upon possible, but unproven IFI. This may cause an overestimation of AFT efficacy. However, even highly effective AFT is unlikely to achieve complete resolution of IFI while patients are still profoundly immunosuppressed, e.g. neutropenic. This inversely may result in an underestimation of AFT efficacy. This dilemma results in the paradigm of very early institution of pre-emptive AFT in high-risk febrile neutropenic patients, i.e. those with lung infiltrates and those not promptly responding to empirical broad-spectrum antibacterial treatment. Taking into account the substantial toxicity of amphotericin B deoxycholate, the extreme expenses associated with less toxic amphotericin lipid compounds, and the yet undefined efficacy of new azoles and candins in invasive aspergillosis, the introduction and validation of new diagnostic techniques for early identification of IFI as well as standardization of case definitions and of criteria for response assessment in patients with IFI appears essential.

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11th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 11th (2001)