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Risk Prediction and Prognosis of Invasive Fungal Disease in Hematological Malignancies Patients Complicated with Bloodstream Infections.

ABSTRACT: Purpose:In patients with hematologic malignancies (HM), bloodstream infections (BSI) and invasive fungal disease (IFD) remain important complications causing considerable mortality and morbidity. At present, the morbidity of IFD and the strategies to initiate antifungal treatment in HM patients with BSI remain unclear. Patients and Methods:Patient characteristics, infection-related variables, and therapy-related features of 1374 HM patients with proven BSI from three hospitals were reviewed to investigate the epidemiology, risk factors and prognosis of IFD. Results:The morbidity of proven and probable IFD in HM patients with BSI was 11.2%, and the mortality of those patients was 40.5%. Existing IFD risk scores were not accurate enough in distinguishing these patients benefiting from antifungal prophylaxis. Multivariate logistic regression identified age >45 years, profound neutropenia, hypoproteinemia, and use of vasopressors as independent variables associated with IFD morbidity in HM patients with BSI. In patients with proven and probable IFD patients, age >45 years, Pitt bacteremia score >3, use of vasopressors, abnormal blood coagulation, and initiation of antifungal therapy within 72 hrs after the onset of fever were independent prognostic factors. The mortality was significantly reduced in patients with high-risk factors of IFD if they initiate antifungal treatment within 72 hrs after the onset of fever compared to the patients not. Conclusion:The morbidity and mortality of IFD increase significantly in HM patients with BSI. Early antifungal therapy may improve prognosis in HM patients with BSI complicated with IFD risk factors.

SUBMITTER: Xiao H

PROVIDER: S-EPMC7102877 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Risk Prediction and Prognosis of Invasive Fungal Disease in Hematological Malignancies Patients Complicated with Bloodstream Infections.

Xiao Han H Tang Yishu Y Cheng Qian Q Liu Jing J Li Xin X

Cancer management and research 20200324

<h4>Purpose</h4>In patients with hematologic malignancies (HM), bloodstream infections (BSI) and invasive fungal disease (IFD) remain important complications causing considerable mortality and morbidity. At present, the morbidity of IFD and the strategies to initiate antifungal treatment in HM patients with BSI remain unclear.<h4>Patients and methods</h4>Patient characteristics, infection-related variables, and therapy-related features of 1374 HM patients with proven BSI from three hospitals wer ...[more]

PMID: 32273756

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Project description:BackgroundPosaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective.MethodsA hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses.ResultsIn the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces.ConclusionsPosaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China.

Project description:BACKGROUND:Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. METHODS:We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. RESULTS:Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28-84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. CONCLUSIONS:Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies.

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Risk Prediction and Prognosis of Invasive Fungal Disease in Hematological Malignancies Patients Complicated with Bloodstream Infections.

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Risk Prediction and Prognosis of Invasive Fungal Disease in Hematological Malignancies Patients Complicated with Bloodstream Infections.

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