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Early antimicrobial prophylaxis in autologous stem cell transplant recipients: Conventional versus an absolute neutrophil count-driven approach.

ABSTRACT:

Background

Autologous hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of developing life-threatening infections. There is discordance in published recommendations for timing of pre- and post-transplant antimicrobial prophylaxis in this patient population, and these recommendations are unsubstantiated by any published comparative analyses.

Methods

An observational, pre- and post-intervention study of consecutive autologous HSCT recipients was conducted over a 2-year period. In the pre-intervention cohort, antimicrobial prophylaxis was initiated on the day prior to transplant. In the post-intervention cohort, antimicrobials were initiated once absolute neutrophil count (ANC) reached ≤500 cells/mm³ . The primary outcome assessed was frequency of febrile occurrences. Secondary outcomes included total days of prophylaxis, positive blood cultures, all-cause mortality, Clostridioides difficile infection rates, and length of stay.

Results

A total of 208 patients were included in the final analysis, with 105 and 103 patients in the pre- and post-intervention cohorts, respectively. The majority of patients included were male. Lower rates of fever occurrences were observed in the post-intervention cohort (83% pre- vs. 69% post-intervention; p = 0.019). A significant reduction in the mean antibacterial days per patient was identified (9.7 vs. 4.6 days; p < 0.001). Other than lower rates of febrile neutropenia in the post-intervention cohort, no differences were identified in secondary outcomes. In multivariable analyses, ANC-driven prophylaxis was independently associated with decreased febrile events.

Conclusions

Delaying prophylaxis until severe neutropenia was not associated with increased febrile events or other secondary clinical outcomes evaluated. This approach is associated with a significant reduction in antimicrobial exposure.

SUBMITTER: Horowitz JG

PROVIDER: S-EPMC9285346 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesInfections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy.SettingThis systematic review included prospective randomised controlled trials and prospective single-arm studies.ParticipantsThe studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018.Primary and secondary outcome measuresPrimary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death.ResultsFrom 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking.ConclusionsOur results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review.Prospero registration numberCRD42017077606.