Early Antibiotic Discontinuation or De-escalation in High-Risk Patients With AML With Febrile Neutropenia and Prolonged Neutropenia

Abstract

Background: There is minimal data evaluating the safety of antibiotic de-escalation in patients with acute myeloid leukemia (AML) with fever and ongoing neutropenia. Therefore, this study evaluated antibiotic prescribing, infection-related outcomes, and patient outcomes of an antibiotic de-escalation initiative. Patients and Methods: This pre–post quasiexperimental study included adult patients with AML hospitalized with febrile neutropenia. An antibiotic de-escalation guideline was implemented in January 2017, which promoted de-escalation or discontinuation of intravenous antipseudomonal β-lactams. The primary outcome assessment was the incidence of bacterial infection in a historical control group before guideline implementation compared with an intervention group after guideline implementation. Results: A total of 93 patients were included. Antibiotic de-escalation occurred more frequently in the intervention group (71.7% vs 7.5%; P<.001), which resulted in fewer days of therapy for intravenous antipseudomonal β-lactams (14 vs 25 days; P<.001). Thirty-day all-cause mortality and length of hospitalization were not different between groups. However, the intervention group had significantly fewer episodes of Clostridioides difficile colitis (5.7% vs 27.5%; P=.007). Conclusions: Implementation of an antibiotic de-escalation guideline resulted in decreased use of intravenous antipseudomonal β-lactams and fewer episodes of C difficile colitis, without adversely impacting patient outcomes. Additional studies are needed, preferably in the form of randomized controlled trials, to confirm these results.

Approach to fever in patients with neutropenia: a review of diagnosis and management

“… 74 , 75 Within the past 6 years since the ESMO guidelines were published, several studies have been published that shed light on appropriate paths forward for appropriate duration of empiric antibiotic therapy in patients presenting with FN ( Table 2 ). 14 – 24 …”

“…Alegria and colleagues performed a pre–post, quasi-experimental trial evaluating a novel de-escalation guideline for AML patients with FN. 17 Pre-implementation patients received physician-directed durations and post-implementation patients’ empiric antibiotics were either de-escalated to fluoroquinolone prophylaxis or discontinued after 5 days of empiric therapy if the patient was afebrile and stable for 48 h. No difference was observed in suspected or documented infection after antibiotic de-escalation or discontinuation, and a decrease in the incidence of Clostridioides difficile infection (CDI) was seen in the post-intervention group (pre 27.5% vs post 5.7%; p = 0.007).…”

“…Over the past decade, several new studies have examined patients with fever and neutropenia. [14][15][16][17][18][19][20][21][22][23][24] In order to best manage patients today, practitioners should be familiar with the most updated diagnostic and treatment information when considering best practices.…”

“…74,75 Within the past 6 years since the ESMO guidelines were published, several studies have been published that shed light on appropriate paths forward for appropriate duration of empiric antibiotic therapy in patients presenting with FN (Table 2). [14][15][16][17][18][19][20][21][22][23][24] Randomized control trials evaluating antibiotic durations in FN patients Only one randomized control trial (RCT) has been performed comparing the relationship between short courses of therapy for FN and clinical outcomes in patients at a high risk for prolonged neutropenia (Table 2). The How Long study conducted by Aguilar-Guisado and colleagues examined clinical outcomes in 157 patients with hematologic malignancy and hematopoietic stemcell transplant (HSCT) presenting with FN without a microbiologic diagnosis.…”

“…Alegria and colleagues performed a pre-post, quasi-experimental trial evaluating a novel deescalation guideline for AML patients with FN. 17 Pre-implementation patients received physiciandirected durations and post-implementation patients' empiric antibiotics were either de-escalated to fluoroquinolone prophylaxis or discontinued after Eleven new studies, including one RCT, have evaluated early discontinuation or de-escalation of empiric antibiotics for patients presenting with FN. Four of the studies used the ECIL-4 recommendations and rates of mortality and other clinical outcomes were similar between patients with early discontinuation and those who continued antibiotics until neutrophil recovery.…”