Risk factors for breakthrough invasive fungal infection during secondary prophylaxis.
BACKGROUND
Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients.


METHODS
From 25 European cancer centres, 166 consecutive patients with acute myelogenous leukaemia (AML) and a recent history of proven or probable pulmonary IFI were included. Patients were followed for recurrence or breakthrough IFI during the subsequent chemotherapy cycle.


RESULTS
Of the 166 patients included, 69 (41.6%) were female, the median age was 53 years (range 2-81) the and 3 (1.8%) were <16 years. Recurrent IFI occurred in 26 patients (15.7%). Multiple logistic regressions yielded predisposing factors: duration of neutropenia [per additional day; odds ratio (OR) 1.043, confidence interval (CI) 1.008-1.078], high-dose cytarabine (OR 3.920, CI 1.120-12.706), number of antibiotics (per antibiotic; OR 1.504, CI 1.089-2.086), partial response as outcome of prior IFI (OR 4.037, CI 1.301-12.524) and newly diagnosed AML (OR 3.823, CI 0.953-15.340). Usage of high efficiency particulate air filter appeared protective (OR 0.198, CI 0.036-1.089).


CONCLUSIONS
Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.
Cornely
Oliver A
OA
Klinik I für Innere Medizin, Klinikum der Universität Köln, 50924 Köln, Germany. oliver.cornely@ctuc.de
Böhme
Angelika
A
Reichert
Dietmar
D
Reuter
Stefan
S
Maschmeyer
Georg
G
Maertens
Johan
J
Buchheidt
Dieter
D
Paluszewska
Monika
M
Arenz
Dorothee
D
Bethe
Ullrich
U
Effelsberg
Jenny
J
Lövenich
Harry
H
Sieniawski
Michal
M
Haas
Antje
A
Einsele
Hermann
H
Eimermacher
Hartmut
H
Martino
Rodrigo
R
Silling
Gerda
G
Hahn
Moritz
M
Wacker
Sidonie
S
Ullmann
Andrew J
AJ
Karthaus
Meinolf
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology* / Q000517:prevention & control*; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
D000935:Antifungal Agents