Modelling and Simulation of the Effect of Targeted Decolonisation on Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections in Haematological Patients

Stefanie Döbele; Fulvia Mazzaferri; Tamara Dichter; Gerolf de Boer; Alex Friedrich; Evelina Tacconelli

doi:10.1007/s40121-021-00550-3

Modelling and Simulation of the Effect of Targeted Decolonisation on Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Bloodstream Infections in Haematological Patients

Infect Dis Ther. 2022 Feb;11(1):129-143. doi: 10.1007/s40121-021-00550-3. Epub 2021 Oct 19.

Authors

Stefanie Döbele^#¹, Fulvia Mazzaferri^#², Tamara Dichter¹, Gerolf de Boer³, Alex Friedrich³, Evelina Tacconelli^{1

4}

Affiliations

¹ Department of Internal Medicine I, DZIF Partner Site, Tübingen University Hospital, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
² Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. fulvia.mazzaferri@univr.it.
³ Department of Medical Microbiology and Infection Control, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
⁴ Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy.

^# Contributed equally.

Abstract

Introduction: Haematological patients are at higher risk of bloodstream infections (BSI) after chemotherapy. The aim of this study was to develop a simulation model assessing the impact of selective digestive decontamination (SDD) of haematological patients colonised with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) on the incidence of ESBL-E BSI after chemotherapy.

Methods: A patient population was created by a stochastic simulation model mimicking the patients' states of colonisation with ESBL-E during hospitalisation. A systematic literature search was performed to inform the model. All ESBL-E carriers were randomised (1:1) to either the intervention (targeted SDD) or the control group (placebo). ESBL-E BSI incidence was the outcome of the model. Sensitivity analyses were performed by prevalence of ESBL-E carriage at hospital admission (low: < 10%, medium: 10-25%, high: > 25%), duration of neutropenia after receiving chemotherapy, administration of antibiotic prophylaxis with quinolones, and time interval between SDD and chemotherapy.

Results: The model estimated that the administration of targeted SDD before chemotherapy reduces the incidence of ESBL-E BSI in the hospitalised haematological population up to 27%. The greatest benefit was estimated in high-prevalence settings, regardless of the duration of neutropenia, the time interval before chemotherapy, and the administration of antibiotic prophylaxis with quinolones (p < 0.05). In medium-prevalence settings, SDD was effective in patients receiving quinolone prophylaxis, with either 1-day time interval before chemotherapy and a neutropenia duration > 6 days (p < 0.05) or 7-day time interval before chemotherapy and a neutropenia duration > 9 days (p < 0.05). No benefit was observed in low-prevalence settings.

Conclusions: Our model suggests that targeted SDD could decrease the rate of ESBL-E BSI in haematological carriers before chemotherapy in the setting of high ESBL-E prevalence at hospital admission. These estimates require confirmation by well-designed multicentre RCTs, including the assessment of the impact on resistance/disruption patterns of gut microbiome.

Keywords: Bloodstream infection; Decolonisation; Enterobacterales; Extended spectrum beta lactamases (ESBLs); Haematological malignancies; Infection control; Modelling; Neutropenia.