Cytokine production and outcome in MDR versus non-MDR gram-negative bacteraemia and sepsis

Abstract

Background

Sepsis represents a life-threatening syndrome characterized by a cytokine storm. Whether cytokine levels are related to the susceptibility pattern of invasive micro-organism remains a matter of debate. The purpose of this study is to investigate the immune response in multidrug resistant (MDR) and non-MDR sepsis patients by measuring cytokine levels, compare the outcome and determine predictors of mortality.

Materials and methods

A total of 128 septic patients, treated in intensive care unit (ICU) were enrolled in the study. Epidemiological and ICU data were recorded. Plasma concentrations of angiopoietin-2 (Ang-2), interleukin (IL)-6, IL-10, tumour necrosis factor-α (TNF-α) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were measured on admission.

Results

A total of 90 patients suffered from non-MDR and 38 from MDR gram-negative sepsis. Levels of TNF-α were significantly higher (p = .017) in non-MDR sepsis patients. All pro-inflammatory cytokines were significantly increased in severely ill patients compared to patients with lower acute physiology and chronic health evaluation (APACHE) II score. MDR positive patients had a significantly lower 28-d survival (p = .008). Factors that were independently associated with higher 28-d mortality were carbapenem resistance (OR 5.38 [1.032 − 28.12], p = .046), male gender (OR 2.76 [1.156 − 6.588], p = .022), APACHE II score (OR 1.126 [1.048 − 1.21], p = .001) and Ang-2 (OR 1.025 [1.001 − 20.1], p = .048).

Conclusions

Sepsis evolution and outcome are influenced by multiple factors. Although MDR pathogens induced a weaker immune response characterized by lower TNF-α levels this was not accompanied by better survival. Increased Ang-2 levels, APACHE II score and carbapenem resistance are important factors associated with higher mortality.

Keywords:

• Sepsis
• cytokines
• tumour necrosis factor-a
• angiopoietin-2
• multidrug resistance
• carbapenem resistance

Disclosure statement

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Acknowledgements

Part of this work was presented at 29th European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) that was held in the Netherlands in April 2019.

Additional information

Funding

This work was funded by the Hellenic Institute for the study of sepsis.