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2015 ; 59
(12
): 7735-42
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In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of
the Mucorales Order
#MMPMID26438494
Arendrup MC
; Jensen RH
; Meletiadis J
Antimicrob Agents Chemother
2015[Dec]; 59
(12
): 7735-42
PMID26438494
show ga
The in vitro activity of isavuconazole against Mucorales isolates measured by
EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison
with those of amphotericin B, posaconazole, and voriconazole. Seventy-two
isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5
of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus,
26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was
confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read
on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2
(CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and
EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively,
across all isolates. The similar values for comparator drugs were as follows:
posaconazole, 0.25 (? 0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16);
amphotericin, 0.06 (? 0.03 to 0.5), 0.06 (? 0.03 to 0.25), and 0.125 (? 0.03 to
1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively.
Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2),
1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to
2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2
(1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8);
and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8),
respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to
8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1
to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole.
The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%).
Isavuconazole displayed in vitro activity against Mucorales isolates with the
exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher
than those for posaconazole. However, in the clinical setting this may be
compensated for by the higher exposure at standard dosing.
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