Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury.

Intestine barrier disruption and bacterial translocation can contribute to sepsis and multiple organ failure, leading causes of mortality in burn-injured patients. In addition, findings suggest that ethanol (alcohol) intoxication at the time of injury worsens symptoms associated with burn injury. We have previously shown that interleukin-22 (IL-22) protects from intestinal leakiness and prevents overgrowth of gram-negative bacteria following ethanol and burn injury, but how IL-22 mediates these effects has not been established. Here, utilizing a mouse model of ethanol and burn injury, we show that the combined insult results in a significant loss of proliferating cells within small intestine crypts and increases Enterobacteriaceae copies, despite elevated levels of the antimicrobial peptide lipocalin-2. IL-22 administration restored numbers of proliferating cells within crypts, significantly increased Reg3ß, Reg3γ, lipocalin-2 AMP transcript levels in intestine epithelial cells, and resulted in complete reduction of Enterobacteriaceae in the small intestine. Knockout of signal transducer and activator of transcription factor-3 (STAT3) in intestine epithelial cells resulted in complete loss of IL-22 protection, demonstrating that STAT3 is required for intestine barrier protection following ethanol combined with injury. Together, these findings suggest that IL-22/STAT3 signaling is critical to gut barrier integrity and targeting this pathway may be of beneficial clinical relevance following burn injury.

Multiple-Drug Resistance in Burn Patients: A Retrospective Study on the Impact of Antibiotic Resistance on Survival and Length of Stay.

Despite improvements in early treatment, survival following burn injury remains challenged by sepsis and multiple organ dysfunction syndrome (MODS). Additionally, susceptibility to infections and growing antibiotic resistance places burn patients at increased risk for infections with multiple-drug resistant organisms (MDROs). We therefore aimed to evaluate the impact of MDRO infections on survival and hospital length of stay, as well as examine the role of these organisms in the development of complications, such as acute kidney injury, sepsis, and MODS. To study this, we included all burn patients with infections, admitted between January 1, 2012, and December 31, 2013. Patients were divided into two groups: patients with infections caused by MDROs and patients with infections caused by susceptible organisms. Data were collected on all available cultures, as well as demographic, injury, and treatment-related variables from the medical record. The number of operative procedures (median: 2 vs 1, P < .0001), ventilator days (21 vs 0 days, P < .0001), total antibiotic days (21 vs 7days, P < .0001), and length of hospitalization (39 vs 14 days, P < .0001) were significantly different in the MDRO group vs the nonresistant group. While MDRO infection was not associated with patient mortality, univariable logistic regression analyses demonstrated >20% TBSA (odds ratio [OR] = 4.30, 95% confidence interval [CI]: 1.14-16.29, P = .03), acute kidney injury (OR = 10.93, 95% CI: 2.74-43.57, P = .001), sepsis (OR = 19.20, 95% CI: 3.79-97.27, P < .001), and MODS (OR = 85.49, 95% CI: 12.97-563.28, P < .0001) significantly increased the odds of patient mortality. These findings suggest that infections with MDROs are associated with a greater number of surgical procedures, longer duration of mechanical ventilation, more antibiotic days, and longer hospitalization.