Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

Abstract

The online version of this article has a Supplementary Appendix. BackgroundGiving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and MethodsThis was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. ResultsEighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. ConclusionsBased on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials. Haematologica 2012;97(3):464-471. doi:10.3324/haematol.2011

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

“…The data were extrapolated from two earlier studies: a prospective cohort study (14) in which PFN episodes were managed following a DDAT approach (12). This DDAT approach included the indication of antifungal therapy following the results of a diagnostic work-up, including clinical signs and/or radiological imaging or microbiological results suggestive of IFI (Fig.…”

“…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 overtreatment and toxic effects, with similar effectiveness to that reported in controlled trials. This approach has been validated prospectively even in a high-risk population (13,14).…”

“…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 overtreatment and toxic effects, with similar effectiveness to that reported in controlled trials. This approach has been validated prospectively even in a high-risk population (13,14).However, although pharmacoeconomic analyses comparing antifungal drugs used in treating PFN have been previously published (15, 16), the cost-effectiveness assessment of new approaches, such as the diagnosis-driven antifungal therapy (DDAT), has not been compared to the standard approach of EAT. Hence, the aim of our study was to evaluate the cost-effectiveness of the DDAT approach in hematological patients with PFN recommended by the SAEI (12) versus the EAT approach recommended by the IDSA guidelines (4).…”

“…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 overtreatment and toxic effects, with similar effectiveness to that reported in controlled trials.…”

The role of antifungal treatment in hematology

“…A prospective study from Spain by Aguilar-Guisado and colleagues challenges this undifferentiated approach. 8 The study established the feasibility of a more tailored diagnostic and therapeutic approach based on clinical criteria other than fever. The strategy had an excellent negative predictive value (correct identification of patients not needing antifungal therapy) for febrile neutropenic patients, resulting in a marked reduction in antifungal consumption without an increase in the overall mortality or fungal-related mortality.…”