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The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model

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Abstract

Introduction

This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB).

Materials and methods

BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay.

Results

Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h.

Conclusion

In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

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Funding

The Erciyes University Scientific Research Project Unit provided funding for this study (Project No: TTU-2021-10624)

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Authors and Affiliations

Authors

Contributions

Fİ, ZT, GD, EE, AHY, DB, and ZBG performed the analysis, collect the data, and prepare material; Fİ, ZT, and GK: collect the patient data; Fİ and ZT wrote the paper; Fİ, ZT, GD, GKÜ, BA, and OY made the critical reviews. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zeynep Ture.

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This study was approved by the Ethical Committee of the University of Erciyes; all subject provided written informed consent (03.06.2020- 20/089).

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All the authors reviewed and approved the final version of the manuscript.

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The authors declare no competing interests.

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İzci, F., Ture, Z., Dinc, G. et al. The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model. Eur J Clin Microbiol Infect Dis 42, 1365–1372 (2023). https://doi.org/10.1007/s10096-023-04674-x

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