In vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order

M. Arendrup, R. H. Jensen, J. Meletiadis

Abstract: 

Background: The in vitro activity of isavuconazole (ISC), a new broad spectrum azole, has been 
studied using the EUCAST methodology against Candida and Aspergillus, however, data on in vitro
activity against Mucorales isolates is sparse. The purpose of this study was to investigate the in vitro
activity against clinical isolates of the Mucorales order by the EUCAST and CLSI methodologies and 
to compare that with the activity of amphotericin B (AMB), posaconazole (PSC) and voriconazole 
(VRC). 


Materials and Methods: 72 clinical isolates were included: Lichtheimia (L) corymbifera 12, L. ramosa
5, Mucor (M) circinelloides (Group I) 5, M. circinelloides (Group II) 9, Rhizomucor pusillus 9, Rhizopus 
(R) microsporus 26 and R. oryzae 6. Species identification was confirmed by ITS DNA sequencing. 
MICs were read visually day 1 and 2 for EUCAST EDef 9.2 and day 2 for CLSI M38-A2 (no visible 
growth day 1). 


Results: MIC50 (MIC range) (mg/L) determined by EUCAST (day 1), CLSI (day 2) and EUCAST (day 
2) for ISC were: 1 (0.125-16); 1 (0.125-2); 4 (0.5->16) across all isolates with a high agreement 
between the EUCAST day 1 and CLSI day 2 MICs. The similar values for the comparator drugs were: 
PSC 0.25 (≤ 0.03->16); 0.25 (0.06->16); 1 (0.06->16), AMB 0.06 (≤ 0.03-0.5); 0.06 (≤ 0.03-0.25); 
0.125 (≤ 0.03-1) and VRC 16 (2->16); 8 (1->16); >16 (8->16) in agreement with the lack of clinical 
efficacy of VRC against Mucorales. Species dependent ISC activity was observed with the lowest 
MICs for: L. corymbifera 1 (0.5-2); 1 (1-2); 2 (1-4), L. ramosa 0.25 (0.125-0.5); 1 (0.5-2); 2 (0.5-4), 
Rhizomucor pusillus 0.5 (0.5-1); 1 (0.125-1); 2 (1-2), R. microsporus 1 (0.5-4); 0.5 (0.125-1); 4 (1-8), 
and R. oryzae 1 (0.5-4); 1 (0.125-2); 4 (0.5-8). The highest MICs were found for M. circinelloides
Group I 8 (4-8); 4 (2-4) and 16 (2-16) and M. circinelloides Group II 8 (1-16); 8 (1-8); 16 (4->16). This 
pattern was also observed for the in vitro activity of PSC but not for AMB. 


Conclusion: ISC displayed in vitro activity against Mucorales isolates with exception of M. 
circinelloides. The MICs were in general 1-3 steps higher than those for PSC. However, in the clinical 
setting this may be compensated by the higher exposure (AUC ranges: ISC: 100 vs PSC 15-35 
mg.h/mL).

abstract No: 

M-1309
    • ICAAC 54th (2014)