TABLE 1.
MICs of posaconazole and MECs of caspofungin based on the CLSI-M38A2 methodologya
| Isolate ID | Disease | Mutation(s)c | Visual reading |
|
|---|---|---|---|---|
| POSA MIC (mg/liter) | CAS MEC (mg/liter) | |||
| v52-35 | Proven invasive aspergillosis | TR34/L98H | 0.5 | 1 |
| v45-07 | Proven invasive aspergillosis | TR34/L98H | 1 | 1 |
| v61-76 | Proven invasive aspergillosis | TR34/L98H | 0.5 | 1 |
| v094-10 | Proven invasive aspergillosis | 46/TR | 0.25 | 0.5 |
| v107-65 | Proven CNS aspergillosis | 46/TR | 1 | 1 |
| v049-29 | Proven Aspergillus osteomyelitis | 53/TR | 0.5 | 1 |
| v059-73 | Clinical isolate (unknown entity) | G54W | >8 | 1 |
| v079-25 | Clinical isolate (unknown entity) | G54W | >8 | 1 |
| 3038 | Proven invasive aspergillosis | M220R | >8 | 0.25 |
| v28-77 | Aspergilloma | M220I | 1 | 1 |
| v59-27 | Allergic pulmonary aspergillosis | M220K | 16 | 1 |
| v13-09 | Probable invasive aspergillosis | M220V | 1 | 1 |
| v59-72 | Aspergilloma | G138C | >8 | 1 |
| AZN 8196 | Proven invasive aspergillosis | — | 0.06 | 0.5 |
| v52-76 | Proven invasive aspergillosis | — | 0.06 | 1 |
| v28-29 | Proven invasive aspergillosis | — | 0.06 | 1 |
| v67-38 (S1)b | Chronic pulmonary aspergillosis | — | 0.06 | 1 |
| v67-37 (S2)b | Chronic pulmonary aspergillosis | — | 0.125 | 1 |
| v67-36 (R1)b | Chronic pulmonary aspergillosis | HapE/P88L | 0.5 | 1 |
| v67-35 (R2)b | Chronic pulmonary aspergillosis | HapE/P88L | 0.5 | 1 |
a
ID, identifier; MEC, minimal effective concentration.
b
These four isolates were cultured consecutively from a single patient (21). Two isolates exhibited a wild-type (WT) susceptibility profile (S1 and S2), while two were azole resistant (R1 and R2). Microsatellite genotyping of all four isolates showed identical genotypes. No cyp51A mutations were found, but a P88L substitution in the CCAAT-binding transcription factor complex subunit HapE seemed to be responsible for the azole-resistant profile (22).
c
—, no mutations in cyp51A and/or hapE.