Impact of reduced antibiotic treatment duration on antimicrobial resistance in critically ill patients in the randomized controlled SAPS-trial

Arezoo Shajiei; Matthijs S Berends; Christian F Luz; Jos A van Oers; Hermie J M Harmsen; Piet Vos; Rob Klont; Bert G Loef; Auke C Reidinga; Laura Bormans-Russell; Kitty Linsen; Tom Dormans; Martine Otten; Akke van der Bij; Albertus Beishuizen; Dylan W de Lange; Evelien de Jong; Maarten W Nijsten

doi:10.3389/fmed.2023.1080007

Impact of reduced antibiotic treatment duration on antimicrobial resistance in critically ill patients in the randomized controlled SAPS-trial

Front Med (Lausanne). 2023 Feb 2:10:1080007. doi: 10.3389/fmed.2023.1080007. eCollection 2023.

Authors

Arezoo Shajiei^{1

2}, Matthijs S Berends^{2

3}, Christian F Luz², Jos A van Oers⁴, Hermie J M Harmsen², Piet Vos⁴, Rob Klont⁵, Bert G Loef⁶, Auke C Reidinga⁶, Laura Bormans-Russell⁷, Kitty Linsen⁷, Tom Dormans⁷, Martine Otten⁸, Akke van der Bij⁹, Albertus Beishuizen¹⁰, Dylan W de Lange¹¹, Evelien de Jong^{12

13}, Maarten W Nijsten¹

Affiliations

¹ Department of Critical Care, University Medical Center Groningen, Groningen, Netherlands.
² Department of Medical Microbiology, University Medical Center Groningen, Groningen, Netherlands.
³ Department of Medical Epidemiology, Certe Foundation, Groningen, Netherlands.
⁴ Department of Intensive Care, Elisabeth-Tweesteden Ziekenhuis, Tilburg, Netherlands.
⁵ Laboratorium Microbiologie Twente Achterhoek, Hengelo, Netherlands.
⁶ Department of Intensive Care, Martini Hospital Groningen, Groningen, Netherlands.
⁷ Department of Intensive Care, Zuyderland Medical Center, Heerlen, Netherlands.
⁸ Department of Intensive Care, Diakonessenhuis Utrecht, Utrecht, Netherlands.
⁹ Department of Microbiology and Immunology, Diakonessenhuis Utrecht, Utrecht, Netherlands.
¹⁰ Intensive Care Center, Medisch Spectrum Twente, Enschede, Netherlands.
¹¹ Department of Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands.
¹² Department of Intensive Care, Beverwijk Hospital, Beverwijk, Netherlands.
¹³ Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, Netherlands.

Abstract

Background: In the previously reported SAPS trial (https://clinicaltrials.gov/ct2/show/NCT01139489), procalcitonin-guidance safely reduced the duration of antibiotic treatment in critically ill patients. We assessed the impact of shorter antibiotic treatment on antimicrobial resistance development in SAPS patients.

Materials and methods: Cultures were assessed for the presence of multi-drug resistant (MDR) or highly resistant organisms (HRMO) and compared between PCT-guided and control patients. Baseline isolates from 30 days before to 5 days after randomization were compared with those from 5 to 30 days post-randomization. The primary endpoint was the incidence of new MDR/HRMO positive patients.

Results: In total, 8,113 cultures with 96,515 antibiotic test results were evaluated for 439 and 482 patients randomized to the PCT and control groups, respectively. Disease severity at admission was similar for both groups. Median (IQR) durations of the first course of antibiotics were 6 days (4-10) and 7 days (5-11), respectively (p = 0.0001). Antibiotic-free days were 7 days (IQR 0-14) and 6 days (0-13; p = 0.05). Of all isolates assessed, 13% were MDR/HRMO positive and at baseline 186 (20%) patients were MDR/HMRO-positive. The incidence of new MDR/HRMO was 39 (8.9%) and 45 (9.3%) in PCT and control patients, respectively (p = 0.82). The time courses for MDR/HRMO development were also similar for both groups (p = 0.33).

Conclusions: In the 921 randomized patients studied, the small but statistically significant reduction in antibiotic treatment in the PCT-group did not translate into a detectable change in antimicrobial resistance. Studies with larger differences in antibiotic treatment duration, larger study populations or populations with higher MDR/HRMO incidences might detect such differences.

Keywords: antibiotics; antimicrobial resistance; culture; procalcitonin; randomized trial; treatment duration.

Associated data

ClinicalTrials.gov/NCT01139489

Grants and funding

Thermo Fisher Scientific was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. AS and CL were funded by CEC MSCA-ITN grant 713660 (Pronkjewail).