Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study

Tan, Ban Hock; Low, Jenny Guek Hong; Chlebicka, Nidhi Loomba; Kurup, Asok; Cheah, Foong Koon; Lin, Raymond Tzer Pin; Goh, Yeow Tee; Wong, Gee Chuan

doi:10.1016/j.ijid.2011.01.011

Cited by 55 publications

(50 citation statements)

References 29 publications

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“…Invasive fungal infections (IFIs) are an important complication in immunocompromised individuals, particularly in neutropenic patients with hematological malignancies 1 . Over the last decades, this group of patients has presented severe infections, which has been the cause of high mortality rate 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Invasive fungal infection in patients with hematologic disorders in a Brazilian tertiary care hospital

Junior

Silva

Arantes

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction: Invasive fungal infections (IFIs) are an important complication in immunocompromised individuals, particularly neutropenic patients with hematological malignancies. In this study, we aimed to verify the epidemiology and diagnosis of IFIs in patients with hematologic problems at a tertiary hospital in Goiânia-GO, Brazil. Methods: Data from 117 patients, involving 19 cases of IFIs, were collected. The collected data included diagnosis methods, demographics, clinical characteristics, and in vitro susceptibility to different antifungal agents. Among the 19 cases, 12 were classified as proven IFI and 7 as probable invasive aspergillosis with detection of galactomannan in blood and presence of lung infiltrates in radiographic images. Logistic regression analysis showed that the proven and probable IFIs were associated with increased risk of death. Statistical analysis demonstrated that age, sex, and underlying disease were not independently associated with risk of death in IFI patients. Results: Most bloodstream isolates of Candida spp. exhibited low minimum inhibitory concentrations (MICs) to all antifungal agents tested. Voriconazole and amphotericin had the lowest MICs for Aspergillus spp. and Fusarium spp., but Fusarium spp. showed the least susceptibility to all antifungals tested. Amphotericin B, fluconazole, and itraconazole were found to be inactive in vitro against Acremonium kiliense; but this fungus was sensitive to voriconazole. Conclusions: Considering the high number of IFI cases, with crude mortality rate of 6%, we could conclude that IFIs remain a common infection in patients with hematological malignancies and underdiagnosed ante mortem. Thus, IFIs should be monitored closely.

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Section: Introductionmentioning

confidence: 99%

Invasive fungal infection in patients with hematologic disorders in a Brazilian tertiary care hospital

Junior

Silva

Arantes

et al. 2017

Rev. Soc. Bras. Med. Trop.

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“…To date, several studies have been compared the cost-effectiveness of different antifungals used in the EAT approach in patients with PFN (15,(27)(28)(29)(30). However, although new approaches have been proposed for the management of this syndrome (8,11,31), none of these studies compared the cost-effectiveness of these new approaches to the standard approach of EAT.…”

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia

Martín-Peña¹,

Gil-Navarro²,

Aguilar‐Guisado³

et al. 2013

Antimicrob Agents Chemother

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e New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and €5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of €32,671 versus €52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more costeffective than the EAT approach in the management of PFN in hematological patients. Invasive fungal infection (IFI) is a serious health problem in hematological patients and hematopoietic stem cell transplant (HSCT) recipients, resulting in a significant morbidity and mortality rate (1-3). Persistent febrile neutropenia (PFN) is a common clinical presentation of IFI in hematological patients. For this reason, during the last 3 decades, the standard approach recommended by the Infectious Diseases Society of America (IDSA) and other international societies for the management of persistent fever in neutropenic hematological patients has been indicating empirical antifungal therapy (EAT) in every patient, with the main objective of improving the outcome of IFI by prompt therapy (4, 5). However, the relatively low incidence of IFI in the whole hematological population, the risk of overtreatment with expensive drugs, and the potential appearance of adverse effects and antifungal resistance selection (6, 7) have made IFIs a safety and economic problem since the optimization of the health care budget is a major priority for all health care systems. Furthermore, the improvement of diagnostic procedures and the efficacy of new antifungal drugs have changed dramatically over the years (8, 9), allowing for new approaches for the management of this syndrome (8,(10)(11)(12)(13)(14), and even updated guidelines consider acceptable other more rational antifungal therapy approaches in a subset of high risk patients, although it is still considered as an experimental practice (4). The Andalusian Society of Infectious Diseases (SAEI) (12) proposed a diagnostic and therapeutic approach based on risk profile and driven by clinical criteria for selecting those patients with PFN who do not need antifungal therapy, avoiding ove...

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“…Finally, Tan et al in a study in 52 episodes in high-risk hematological patients concluded that a preemptive approach may reduce empirical antifungal use without differences in twelve-week survival rates in persistently febrile neutropenic patients, but this work did not include children [71] . We rarely use preemptive therapy because of the high false positive rate of GM and Aspergillus PCR.…”

Section: Preemptive Treatmentmentioning

confidence: 99%

Invasive fungal diseases in children with hematological malignancies and stem cell transplant recipients

et al. 2012

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Invasive Fungal Disease (IFD) remains a major cause of morbidity and mortality in patients with hematological malignancies or undergoing stem cell transplantation. New surrogate markers of IFD -galactomannan antigen, β-D-glucan, fungal polymerase chain reaction…-and the availability of modern antifungal drugs have changed the management of this serious complication, but both have limitations in children. There are still some unclear issues, particularly in pediatric patients, regardless of the medical and economic possibilities of hospitals: IFD remains difficult to diagnose in a timely way, stem cell transplant recipients have different risk of IFD, antifungal drugs are not free from adverse effects and prospective studies in children are scarce. In this sense, diagnosis criteria have to be assessed, risk stratification should be redefined and the different types of prophylaxis/treatment -prophylaxis, preemptive, empiric and targeted treatment-must be used correctly. We consider low risk for IFD children undergoing autologous stem cell transplantation and children with acute lymphoblastic leukemia; both should receive fluconazole as primary prophylaxis and empiric therapy with an agent with activity against mold. In those who undergoing allogeneic stem cell transplantation or chemotherapy for acute myeloid leukemia, prophylaxis should be performed with a mold active agent -triazoles priority-. We rarely use preemptive therapy because of a high false positive rate of galactomannan. In proven and probable IFD we use targeted therapy, selecting a drug based on the type of infection, sensitivity to the drug in our hospital and prior antifungal prophylaxis/treatment. In selected patients, antifungal combination therapy should be a valid option. Despite great advances, there are still thought provoking questions on the diagnosis and management of IFD in children with hematological diseases.

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Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study

Abstract: A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

Cited by 55 publications

References 29 publications

Invasive fungal infection in patients with hematologic disorders in a Brazilian tertiary care hospital

Invasive fungal infection in patients with hematologic disorders in a Brazilian tertiary care hospital

Cost-Effectiveness Analysis Comparing Two Approaches for Empirical Antifungal Therapy in Hematological Patients with Persistent Febrile Neutropenia

Invasive fungal diseases in children with hematological malignancies and stem cell transplant recipients

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