TABLE 1.

Clinical characteristics of patients with Candida breakthrough infection receiving micafungin at DUMC, February 2006 to May 2008a

PtAge (yr)SexUnderlying disease in hostIndication for micafunginBreakthrough Candida spp.Time from transplant to breakthrough infectionb (days)Contiguous micafungin exposure (days)Total micafungin exposurec (days)Site(s) of cultureLikely source of infectionBreakthrough infection treatment/outcomePatient outcome (days postbreakthrough)
147MMM s/p auto-HSCTFN C. parapsilosis; C. krusei 1655BloodAbdomen or CVCFailed ABLC (5 d) and CVC removalDied (9): Pseudomonas/Candida sepsis
220MDBA s/p allo-HSCT w/GVHDFN C. parapsilosis 412222BloodCVCFailed various combination antifungals including LAMB, FLU, VORI, and MCF and CVC removalDied (22): C. parapsilosis/VRE sepsis
321MNHL, CTCL s/p allo-HSCT w/GVHDProphylaxis C. glabrata 246165165BloodCVCSuccess w/VOR (14 d) and CVC removalDied (19): VZV encephalitis, recurrent CTCL
418FALL/MDS s/p 2nd allo-HSCT w/GVHDTreatment for C. parapsilosis-infected lung hematoma C. parapsilosis 28414104BloodCVCSuccess w/LAMB (8 wks) and CVC removal (continued as prophylaxis)Died (73): MOF; respiratory failure with parainfluenza virus
525FMLD s/p allo- HSCT w/GVHDTreatment for C. glabrata vaginitis C. glabrata 1902043BloodVagina or CVCSuccess w/LAMB (8 d) and CVC removal after failing combination FLU/VOR + MCF for 44 dDied (62): MOF, progressive MLD
645MOLT w/primary graft failureProphylaxis C. glabrata 732143BloodAbdomenDied prior to knowledge of breakthrough infectionDied (1): graft failure, C. glabrata sepsis
749MOLT #3 w/primary graft failureEmpirical for sepsis, continued as prophylaxis C. glabrata; C. parapsilosis 2822Ascites; abdominal fasciaAbdomenSuccess w/53 d of ABLCDied (115): graft failure, VRE/Pseudomonas sepsis
860MOLT #2 w/primary graft failureEmpirical for sepsis, continued as prophylaxis C. parapsilosis; C. glabrata d 7; 2119; 019; 22Blood/biliary fluid; bloodAbdomenFailed combination LAMB + FLUDied (12): graft failure, C. glabrata sepsis
954FBOLTProphylaxis C. parapsilosis 2520e 20BloodCVC or infected clotSuccess w/21 d of LAMB after failing 15 d of VOR and CVC removalDied (62): MOF, VRE sepsis
1064MBOLTTreatment for C. albicans and C glabrata fungemia C. albicans; unspecified yeast342828Pleural fluid; lung tissuef Pleural space/lungSuccess w/MCF (150 mg/d) + inhaled ABLC followed by 150 d FLUSurvived; alive and well at day 480
1165FBOLTEmpirical for sepsis after prior treatment for IC C. dubliniensis; C. tropicalis 1021056Pleural fluid; blood/pleural fluidPleural spaceDied after only 1 dose of ABLCDied (2): disseminated candidiasis
1245FVentral hernia infectionProphylaxis C. tropicalis NA3737BloodAbdomen or CVCSuccess w/ABLC (14 d) and CVC removalDied (24): polymicrobial (bacterial) sepsis
  • a ABLC, amphotericin B lipid complex; ALL, acute lymphoblastic leukemia; allo, allogeneic; AML, acute myelogenous leukemia; ANF, anidulafungin; auto, autologous; BOLT, bilateral orthotopic lung transplant; CAS, caspofungin; CTCL. cutaneous T-cell lymphoma; CVC, central venous catheter; d, day(s); DBA, diamond-blackfan anemia; F, female; FN, febrile neutropenia; GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; IC, invasive candidiasis; LAMB, liposomal amphotericin B; M, male; MCF, micafungin; MDS, myelodysplastic syndrome; MLD, metachromatic leukodystrophy; MM, multiple myeloma; MOF, multiorgan failure; NA, not applicable; NHL, non-Hodgkin lymphoma; OLT, orthotopic liver transplant; Pt, patient number; s/p, status post; VRE, vancomycin-resistant enterococcus; VZV, varicella-zoster virus; w/, with.

  • b For patients that received >1 transplant, the date of the most recent transplant was used. In all cases involving multiple Candida species except case 8, isolates were recovered within 2 days of each other.

  • c Total micafungin exposure over the 6 months prior to breakthrough IC.

  • d For patient 8, C. glabrata isolates were recovered 14 days after the initial C. parapsilosis breakthrough infection; this occurred after MCF was discontinued in favor of LAMB plus FLU combination therapy. The C. glabrata isolates are not included in the analysis of days from transplant to breakthrough infection or duration of contiguous micafungin exposure. MLST of both C. glabrata isolates revealed ST3, a common global C. glabrata strain type. The isolates also had identical FKS gene sequences and echinocandin MICs but different morphology types and disparate azole MICs (fluconazole and voriconazole MICs [μg/ml] for the 1st isolate were 16 and 0.75, while MICs for the 2nd isolate were >256 and >32, respectively). Thus, each isolate is presented individually.

  • e For patient 9, the first 10 days of echinocandin therapy were with anidulafungin, followed by 10 days of micafungin.

  • f Patient 10 had C. albicans recovered from pleural fluid and intra-alveolar yeast visualized on histopathology of lung tissue.