Volume 15, Number 7—July 2009
Research
Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure1
Table 3
Cyp51A amino acid substitutions and associated cross-resistance patterns in azole-resistant RMLM Aspergillus fumigatus isolates*
| Cyp51A codon | No. patients | No. isolates | Amino acid substitutions | MIC, mg/L† |
||
|---|---|---|---|---|---|---|
| Itraconazole | Voriconazole | Posaconazole | ||||
| F46‡ | 3 | 4‡ | Y | >8 | 2–4 | 0.125–0.5 |
| G54 | 4 | 5 | E, R, V | >8 | 0.125–1 | 1–>8 |
| L98+TR | 2 | 2 | H | >8 | 8 | 1–2 |
| G138 | 1 | 10 | C | >8 | 8–>8 | 2–>8 |
| H147§ | 1 | 1§ | Y | >8 | >8 | 0.5 |
| M172‡ | 3 | 4‡ | V | >8 | 2–4 | 0.125–0.5 |
| P216 | 1 | 1 | L | >8 | 1 | 1 |
| M220 | 3 | 4 | K, T | >8 | 1–4 | 0.5–>8 |
| N248‡ | 1 | 1 | T | >8 | 2 | 0.25 |
| D255‡ | 1 | 1 | E | >8 | 2 | 0.25 |
| E427‡ | 4 | 5‡ | G, K | >8 | 2–4 | 0.125–0.5 |
| Y431 | 1 | 1 | C | >8 | 4 | 1 |
| G434 | 1 | 1 | C | >8 | 4 | 1 |
| G448 | 2 | 2 | S | >8 | >8 | 0.5–1 |
| No substitutions | 2 | 3 | NA | >8 | 2–8 | 0.25–1 |
*RMLM, Regional Mycology Laboratory Manchester; TR, tandem repeat in cyp51A promoter; NA, not applicable. Synonymous mutations not shown. Some mutations are associated with resistance but may not be causal (see text).
†Putative cut-off values for resistance are itraconazole and voriconazole >2 mg/L and posaconazole >0.5 mg/L.
‡F46Y found with M172V and E427K in 4 isolates along with 3 silent mutations. E427G seen alone in 1 isolate. N248 and D255 found in combination with 46/172/427 in 1 isolate.
§Found with G448S in 1 of 2 isolates.
1These data were presented in part at the 2nd Advances Against Aspergillosis meeting, February 22–26, 2006, Athens, Greece; and 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 27–30, 2006, San Francisco, CA, USA.