Evaluation of empiric antibiotic de-escalation in febrile neutropenia

Kroll, Amanda; Corrigan, Patricia; Patel, Shejal; Hawks, Kelly G.

doi:10.1177/1078155215597558

Cited by 26 publications

(31 citation statements)

References 5 publications

(17 reference statements)

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“…On the contrary, Micol et al [16] prematurely interrupted their study in neutropenic patients with acute myeloid leukemia and fever of unknown origin because 3 of 7 patients demonstrated fever relapse within 3 days from antibiotic discontinuation and 1 developed septic shock. However, these results are in contrast with a retrospective study in neutropenic patients and our experience, in which 19% and 17.5% of patients needed subsequent escalation of antibiotics but no case of severe infection (severe sepsis or shock) or death occurred [13]. More importantly, the recent RCT on discontinuation also found no differences in the number of days with fever, severe adverse event, or death noted between the 2 study arms [9].…”

Section: Discussioncontrasting

confidence: 90%

“…Almost all studies have been performed in intensive care units (ICUs), and definitions and timing of de-escalation varied significantly [10]. In addition, only few studies and 1 recent randomized trial have focused on neutropenic cancer patients [9,[11][12][13][14], but very limited data are currently available on the pre-engraftment period in HSCT. The safety of discontinuation of empirical treatment before the resolution of neutropenia has also been a source of debate [15,16].…”

Section: Introductionmentioning

confidence: 99%

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De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

Gustinetti

Raiola

Varaldo

et al. 2018

Biology of Blood and Marrow Transplantation

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To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n = 58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n = 24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n = 26) and mostly consisted of reducing the spectrum of β-lactams (n = 11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n = 31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n = 57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT.

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Section: Discussioncontrasting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

Gustinetti

Raiola

Varaldo

et al. 2018

Biology of Blood and Marrow Transplantation

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“…3), though these events were too infrequent to draw definitive conclusions. Kroll et al also retrospectively looked at BSA de-escalation in patients who remained neutropenic after HSCT, but patients could not be de-escalated until after they had already received 14 days of BSA, bringing into question whether this was truly a de-escalation strategy [19].…”

Section: Discussionmentioning

confidence: 99%

De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia

et al. 2020

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Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early deescalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.

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“…The primary end point was rate of recurrent fever within 72 hours of antimicrobial de-escalation. A 72-hour time frame was chosen as it has been previously utilized in an effort to minimize inclusion of any fever or antimicrobial re-escalation secondary to new infectious and/or noninfectious causes [ 21 ]. This period occurred at a different time point for every individual patient.…”

Section: Outcomes and Trial Designmentioning

confidence: 99%

“…A commonly cited rationale for this is the theoretical concern that stopping broad-spectrum therapy early may increase the potential for recurrent infection and subsequent need for re-escalation of antimicrobials, as cited in an early work by Pizzo and colleagues [ 12 ]. However, these concerns have been demonstrated to be unfounded in several subsequent studies [ 21–23 ].…”

mentioning

confidence: 99%

Early Antimicrobial De-escalation and Stewardship in Adult Hematopoietic Stem Cell Transplantation Recipients: Retrospective Review

Snyder

Pasikhova

Baluch

2017

Open Forum Infectious Diseases

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BackgroundAntimicrobial stewardship in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients remains underutilized in North America. European guidelines advise de-escalation of broad-spectrum therapy after 72 hours in select patients with neutropenic fever of unknown origin. This is not commonplace in the United States, as current guidelines recommend broad-spectrum therapy until neutrophil engraftment. If de-escalating after at least 5 days of broad-spectrum therapy and defervescence in neutropenic allo-HSCT recipients does not predispose them to recurrent fever or infection, the practice could afford several benefits.MethodsThe primary end point was rate of recurrent fever. Secondary outcomes included Clostridium difficile–associated infections, length of stay, intensive care unit (ICU) admission incidence, in-hospital mortality rate, need for re-escalation of therapy, rate of positive blood cultures for patients who had recurrent fevers, overall antimicrobial utilization from neutropenic fever onset, and pharmacoeconomic impact.ResultsA total of 120 patients were assessed in 2 groups as cohort 1 (n = 46), which received early de-escalation, and cohort 2 (n = 74), which did not. The primary end point met criteria for noninferiority, as 7 patients (15%) in cohort 1 had recurrent fever within the specified time frame compared with 14 (19%) in cohort 2 (90% CI, –0.0878 to 0.1629, P = .026). Patients in cohort 1 received significantly less gram-positive broad-spectrum antimicrobials, with trends toward lower use of broad-spectrum gram-negative agents and lower associated costs and no differences in length of stay, ICU admission incidence, need for re-escalation of therapy, rate of culture-positive bacteremia after de-escalation or discontinuation of broad-spectrum therapy, or in-hospital mortality rate.ConclusionsDe-escalating after at least 5 days of broad-spectrum therapy and defervescence did not appear to affect the rate of recurrent fever. This allowed for significant reductions in gram-positive broad-spectrum antimicrobial utilization, with trends toward lower use of broad-spectrum gram-negative agents and associated costs and no difference in clinical outcomes compared with those continuing such therapy until neutrophil engraftment.

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Evaluation of empiric antibiotic de-escalation in febrile neutropenia

Abstract: Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.

Cited by 26 publications

References 5 publications

De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia

Early Antimicrobial De-escalation and Stewardship in Adult Hematopoietic Stem Cell Transplantation Recipients: Retrospective Review

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