Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13–0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38–0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.
Background: Posaconazole prophylaxis in patients with acute myeloid leukaemia (AML) changed the paradigm of fungal infections (FI). Aims: Description of FI and analysis of factors that might predispose to this type of infection in non-allotransplant AML patients in the posaconazole era.Methods: Retrospective analysis of 144 consecutive non-M3 AML patients diagnosed between January 2012 and June 2018 in a tertiary center and treated with intensive chemotherapy regimens with posaconazole prophylaxis, including autologous transplantation when performed in these patients. Multivariate regression analysis was performed to identify characteristics related to FI. Results: Median age at diagnosis was 52 years [19;71], 52% were females and 90% had an age-adjusted Charlson score ≤3. Genetic risk group according to the European Leukemia Net 2017 classification was favourable in 28%, intermediate in 41% and adverse in 22%. Fourteen percent of patients (n = 20) had secondary AML. Patients were included since diagnosis and if completed remission-induction intensive therapy up to transplant referral, the latter which occurred in 52% of patients (n = 75), with a median follow-up of 7 months [1;81]. Only 7 patients had 1 episode of prophylaxis interruption, 3 due to mucositis and 4 out of our protocol. Median time of neutropenia per cycle was 26 days [5;180] and 10% of patients had >2 episodes of prolonged neutropenia (defined as ≥28 consecutive days of <500 neutrophils/microliter). Fungal infections were identified in 25 patients (17.4%) and classified according to EORTC criteria, with 5 proven, 13 probable and 7 possible infections. In 32% of patients FI occurred during remission-induction (n = 8) of which 3 were diagnosed in the first week of neutropenia, 20% during consolidation treatment in first remission and 48% during relapse treatment. Of the confirmed infections, 3 were aspergillosis and 2 candidemia. Probable infections had pulmonary origin with no microbiology isolate or serologic positivity but identified by typical radiologic evidence; of these, broncho-alveolar lavage and/or pulmonary biopsy was performed in 4 patients (31%) with negative results. For possible infections, antifungal therapy was initiated in a pre-emptive manner for high risk patients with persistent fever despite large spectrum antibiotics. In a multivariate analysis, patients with FI had a higher odds of having relapsed AML and >2 episodes of prolonged neutropenia during treatment (p = 0.049 and p = 0.011, respectively). There was no mortality related to FI in this cohort of patients. Summary/Conclusion: Despite posaconazole prophylaxis, FI is still prevalent in AML patients. Infection during salvage treatment for relapsed disease and >2 previous periods of neutropenia exceeding 4 weeks should raise awareness for an increased risk of FI.
Background:Heart failure is associated with activation of thrombin‐related pathways, which predicts a poor prognosis, this activation may contribute to disease progression by inducing inflammation, endothelial dysfunction, and arterial and venous thrombosis. Besides, Atrial Fibrillation, one of the most important indications of anticoagulant treatment appears frecuently in patients with heart failure.Aims:To analyse the influence of the previous treatment with oral anticoagulants in the early mortality in patients with acute heart failure.Methods:Multicenter, prospective cohort study of consecutive inclusion of patients with acute heart failure (AHF) attended in Spanish SUH. The diagnosis of AHF was made based on criteria of the European Society of Cardiology. They were divided according to whether they were receiving home treatment with oral anticoagulants (ANTICAGULATED group) or not (CONTROL group). The dependent variable was mortality at 30 days and a year. Variables: Age and sex, systolic blood pressure (PAS), cardiac and respiratory frequencies and oxygen basal arterial saturation, cardiovascular risk factors and previous cardiovascular diseases, basal NHYA and episode, clinical episode data, Analytical and ECG parameters, Troponins, natriuretic peptides, hospital admission and CHADS‐Vasc.Statistical analysis: Comparison of proportions by Chi‐square, averages by T‐student and multivariate analysis by logistic regression and survival through the Cox method and pairing through a propensity score between the two groups of Treatment, adjusting by the variables with p < 0.05 in the Bivariate analysis and controlling the reference hospital.Results:13366 patients with AHF were included, in treatment with oral anticoagulants 5471 (39.7%). In the ANTICOAGULATED‐group there are more comorbility (hypertension, diabetes, ischemic cardiopathy, valvular cardiopathy, atrial fibrillation, cerebro‐vascular disease and previous heart failure). They have poor functional status to disnea (NYHA III‐IV) and more frailty.The clinical data of the acute episode were less severe in the anticoagulated group and had lower values of NT‐ProBNP and Troponins. OR (IC95%) Crude and adjusted mortality to 30 days is 0.64 (IC95% 0.54–0.77) and 0.69 (IC95% 0.54–0.89) and for the annual mortality 0.78 (IC95% 0.69–0.87) and 0.71 (IC95% 0.60–0.84) crude and adjusted respectively. After the propensity Score matching 2330 patients were matched without any difference between them in the analyzed variables. The Hazard Ratio (HR) (IC95%) For the 30‐day mortality of oral anticoagulant therapy is 0.66 (IC95% 0.50–0.85) and for annual mortality 0.79 (IC95% 0.68–0.92).Summary/Conclusion:Treatment with oral anticoagulants in patients with AHF is related to a lower early and annual mortality independently of the differences between the two groups of patients. This may be due to the effect of this treatment on the state of hypercoagulation described in patients with this pathology.
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