ObjectivesInvasive fungal infections (IFIs) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for haematological malignancies. The present study investigates the overall survival (OS), infection-related mortality and changes in treatment of IFIs in our department from 1995 until 2006.MethodsOutcomes of all chemotherapy courses were retrospectively evaluated using a standard questionnaire. Modified EORTC/MSG criteria for IFIs were applied: a positive PCR result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI.ResultsIn total, 1693 chemotherapy courses in 592 patients were evaluated. Sixty-three percent of chemotherapy courses were given to treat acute myeloid leukaemia, with the rest for acute lymphoblastic leukaemia or aggressive lymphoma. IFIs were observed in 139/592 patients [23.5%, 95% confidence interval (CI) 20%–27%] and in 149/1693 courses (8.8%, 95% CI 8%–10%). IFI-related mortality was 56.9% in 1995–2001 and 28.6% in 2002–06, P < 0.001. Accordingly, median OS in patients with IFI increased: 54 days (95% CI 26–82 days) in 1995–2001 versus 229 days (95% CI 35–423 days) in 2002–06, P = 0.001. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy [hazard ratio (HR) 0.228, P < 0.001], possible IFI (in contrast to proven/probable IFI, HR 0.537, P = 0.005), age <60 years (HR 0.583, P = 0.008), time period 2002–06 (HR 0.612, P = 0.021) and use of novel antifungals (HR 0.589, P = 0.033).ConclusionsCompared with 1995–2001, IFI-related mortality decreased and OS in patients with IFI increased significantly in recent years. Improved OS was associated with controlled haematological disease, certainty of IFI diagnosis (possible), younger age, time period 2002–06 and the use of novel antifungals.
The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.
Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis.
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