In vitro susceptibilities and genotypes of breakthrough isolatesa

Patient no.Breakthrough Candida speciesSite of cultureMIC (μg/ml)bFksp amino acid substitutionc
1 C. parapsilosis Blood414None
C. krusei Blood0.2510.251: H675H/Qd
2 C. parapsilosis Blood818None
3 C. glabrata Blood8>1681: S629P
4 C. parapsilosis Blood414None
5 C. glabrata Blood4>1642: S663P
6 C. glabrata Blood0.250.250.25None
7 C. parapsilosis Abdominal fascia20.51None
C. glabrata Ascites4442: S663F
8 C. parapsilosis Blood40.54None
C. parapsilosish Biliary fluid
C. glabrata e Blood8>1682: S663P
C. glabrata e Blood4>1642: S663P
9 C. parapsilosis Blood414None
10 C. albicansh Pleural fluid
11 C. dubliniensis Pleural fluid0.060.250.061: L635V + T655Ad
C. tropicalis f Blood4821: S80S/Pg
C. tropicalis f Pleural fluid2421: S80S/Pg
12 C. tropicalis Blood0.120.250.06None
  • a ANF, anidulafungin; CAS, caspofungin; MCF, micafungin.

  • b Susceptibility testing was performed using the M27-A3 broth microdilution method (9).

  • c The number preceding the colon has the following meanings: 1 denotes FKS1, and 2 denotes FKS2. The first letter and following 3-digit number represent the wild-type amino acid for that position in the protein; the last letter denotes the resultant amino acid change from the gene mutation. In cases of diploid organisms, heterozygous mutations are annotated by 2 letters (example, S/P).

  • d Outside the “hot-spot” regions.

  • e Patient 8 C. glabrata breakthrough isolates obtained 14 days after the initial C. parapsilosis breakthrough infection; the patient was receiving liposomal amphotericin B, 5 mg/kg of body weight/day, and FLU, 400 mg/day, at the time of recovery. See Table 1, footnote d, and the primary text for further details.

  • f Patient 11 C. tropicalis was presumptively the same strain isolated from different sites (same FKS gene sequence and MICs to azoles and echinocandins within one dilution, and identical, unusual MLST sequence type [ST6]).

  • g For Fks1p, the C. tropicalis S80S/P amino acid substitution is the C. albicans S645S/P amino acid substitution equivalent.

  • h Breakthrough isolate not available.