Posaconazole resistance Sample Clauses

Posaconazole resistance. Although the use of azole monotherapy is precluded in most patients with azole- resistant Aspergillus disease, a modest role of azole therapy may remain in infections caused by isolates with low-level azole resistance. If the azole MIC is close to the resistance breakpoint, dose escalation might be a feasible strategy provided that drug toxicity is avoided. The posaconazole MICs of azole-resistant A. fumigatus often remain close to the wild-type MIC distribution (i.e. MIC ≤0.5 to 1 mg/L) [115, 116]. Preclinical studies indicated that isolates with a posaconazole MIC of 0.5 mg/L can be treated successfully with increased exposure [7, 9]. The required AUC/MIC in patients to treat isolates with increased posaconazole MICs was calculated based on these experiments and bridged to human infections. Thus for each posaconazole MIC the required exposure was calculated. As the posaconazole AUC is linearly correlated with Cmin, target Cmin values could be extracted from this correlation [97]. Thus, it is postulated that these isolates with relatively low MICs (but classified as resistant based on the EUCAST breakpoint) may be treated with augmented posaconazole dosing in order to achieve high drug concentrations [23]. One should bear in mind that clinical evidence on the efficacy of this strategy is absent. A major concern of a strategy using augmented dosing is the revelation of adverse events (AEs). One study evaluated the AE in patients with posaconazole high dosing regimen and incidental high posaconazole serum concentrations. This study concluded that the number of AEs in these groups were comparable to previous reports on standard dosing. A direct comparison between high dosing and standard dosing has not been reported [23].