Treatment of Aspergillus terreus infections: a clinical problem not yet resolved

Despite the use of recommended therapies, invasive infections by Aspergillus terreus show a poor response. For years, investigative studies on the failure of therapy of fungal infections have focused on in vitro susceptibility data. However, it is well known that low minimum inhibitory concentrations (MICs) are not always predictive of response to therapy despite a correct dosage schedule. Many experimental and clinical studies have tried to establish a relationship between MICs and outcome in serious fungal infections but have come to contradictory and even surprising conclusions. The success or failure of treatment is determined by many factors, including the in vitro susceptibility of the causative fungal isolate, the pharmacokinetics/pharmacodynamics of the drug used for treatment, pharmacokinetic variability in the population, and the underlying disease that patients suffer. To try to understand this poor response to treatment, available data on the in vitro susceptibility of A. terreus, the experimental and clinical response to amphotericin B, triazoles and echinocandins, and the pharmacokinetics/pharmacodynamics of these antifungals have been reviewed. Of special interest are the fungistatic activites of these drugs against A. terreus and the high interpatient variability of serum drug levels observed in therapy based on triazoles, which make monitoring of infected patients necessary.