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

Infect Dis (Lond). 2021 Oct;53(10):764-771. doi: 10.1080/23744235.2021.1925738. Epub 2021 Jun 17.

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; angiopoietin-2; carbapenem resistance; cytokines; multidrug resistance; tumour necrosis factor-a.

MeSH terms

  • Bacteremia* / drug therapy
  • Cytokines
  • Female
  • Humans
  • Male
  • Prognosis
  • Prospective Studies
  • Sepsis* / drug therapy
  • Tumor Necrosis Factor-alpha

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha