A cohort study on breakthrough invasive fungal infections in high-risk patients receiving antifungal prophylaxis.
Antifungal prophylaxis is recommended for haematological patients at high risk of invasive fungal infections (IFIs). Incidence, optimal therapeutic management and outcome of breakthrough IFIs (bIFIs) are largely unknown.



To assess bIFI incidence, treatment and outcomes, data on patients undergoing AML remission-induction and consolidation chemotherapy and from allogeneic HSCT recipients on antifungal prophylaxis with itraconazole, micafungin or posaconazole were extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut). bIFIs were classified according to revised EORTC/MSG criteria.



From January 2004 to April 2013, 250 AML patients with 329 hospitalizations and 409 HSCT patients with 496 hospitalizations were identified. In AML patients, there were 16 (6.4%) proven or probable bIFIs and 44 (17.6%) possible bIFIs. In HSCT patients, there were 14 (3.4%) proven or probable bIFIs and 37 (9.0%) possible bIFIs. Proven cases included five candidaemias, two mucormycoses, three aspergilloses and one fusariosis. The most frequent choice for bIFI treatment was liposomal amphotericin B in AML patients (21/60; 35.0%) and continuation of posaconazole prophylaxis in HSCT patients (16/51; 31.4%). In HSCT recipients, survival on day 365 was significantly lower in bIFI patients (AML, 63.3% versus 70.0%; P = 0.297; HSCT, 49.0% versus 66.8%; P = 0.012). Comparison of continuation of prophylaxis versus switch of antifungal class as first-line treatment showed no significant difference regarding response to treatment and survival.



Rates of bIFIs observed in our population were comparable to previous data. There was no clear shift towards rare species, as previously reported. A high variety of treatment approaches was observed.
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany German Centre for Infection Research, partner site Bonn-Cologne, Germany.
Lena M
LM
Biehl
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany German Centre for Infection Research, partner site Bonn-Cologne, Germany.
J Janne
JJ
Vehreschild
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Blasius
B
Liss
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Bernd
B
Franke
Institute for Pathology, University Hospital of Cologne, Cologne, Germany.
Birgid
B
Markiefka
Department of Radiology, University Hospital of Cologne, Cologne, Germany.
Thorsten
T
Persigehl
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Vanessa
V
Bücker
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Hilmar
H
Wisplinghoff
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Christof
C
Scheid
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany German Centre for Infection Research, partner site Bonn-Cologne, Germany Center for Integrated Oncology, CIO KölnBonn, University of Cologne, Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Oliver A
OA
Cornely
Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany German Centre for Infection Research, partner site Bonn-Cologne, Germany maria.vehreschild@uk-koeln.de.
Maria J G T
MJ
Vehreschild
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D015331:Cohort Studies; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000150:complications; D006801:Humans; D015994:Incidence; D000072742:Invasive Fungal Infections / Q000453:epidemiology* / Q000517:prevention & control*; D017964:Itraconazole / Q000627:therapeutic use; D055666:Lipopeptides / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D014230:Triazoles / Q000627:therapeutic use; D055815:Young Adult
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D000077551:Micafungin