Objectives: Here we describe first clinical case of a caspofungin resistant C. glabrata infection. The patient was a 43 year old male withAML.He received amatched unrelatedHSCT, 9 months prior to his death. He had a complicated hospital coursewhich included C. glabrata sepsis. C. glabrata was cultured from his stool, from the time of transplant to death. Initial blood culture isolateswere azole resistant andAmphotericin Bwas started. Thiswas stopped due to renal insufficiency and caspofunginwas started (MIC 0.12 lg/ml). He had a prolonged duration of therapy which comprised of alternating courses of IV voriconazole and caspofungin. Four months after initial fungaemia C. glabrata was cultured which wasboth caspofungin resistant (MIC > 8lg/ml) and azole resistant. Despite the addition of amphotericin B the patient died 8 weeks later. C. glabrata was isolated from the bone marrow at autopsy. Methods: The series of patient isolates, from time of transplant to death, had susceptibilities performed as per NCCLS document M27-A. The isolates were typed using Cg6 probe and MLST. Results: he susceptibilities demonstrated caspofungin resistance in the blood isolate ( > 8 lg/ml) and azole resistance in all but a few of the initial stool isolates. All the isolates were shown to be identical by Cg6 and were determined to be MLST group 1, which has previously been shown to be the most prevalent clade of C. glabrata worldwide. Discussion: This describes the first caspofungin resistant clinical isolate of C. glabrata. It has been recently reported in C. albicans. This data details an isolate that has developed resistance in the presence of therapy. Resistance to caspofungin is not common and is thought to be due tomutations in the beta-13-glucan synthase (FKS) gene. There are 3 FKS genes in C. glabrata. Preliminary sequencing data of one of these genes has so far revealed no non-conservative mutations. The 2 remaining genes are yet to be sequenced and the presence of other mechanisms cannot be ruled out.
Full conference title:
- ECCMID 15th (2005)