Burn patients are at high risk of infections due to severe impairment of immunity and loss of skin barrier function. We aimed to describe the epidemiology, incidence and risk factors for infection in a cohort of burns patients. Two hundred patients were retrospectively enrolled and subdivided into infected (N = 81) and uninfected groups (N = 119). The cumulative prevalence of infections was 27% on day 7 and 43.8% on day 28. Skin and soft tissue infections (32%) were the most frequent. Carbapenem-resistant Acinetobacter baumannii (28%), Pseudomonas aeruginosa (26%) and methicillin-resistant Staphylococcus aureus (25%) infections were most prevalent. An indwelling central venous catheter (CVC; sub-hazard ratio [SHR] 7.41, 95% confidence interval [CI] 3.78–14.62) and revised Baux score (RBS; SHR 2.08, 95% CI 0.98–4.42) were associated with higher incremental infection rate while surgical treatment resulted in a protective factor (SHR 0.45, 95% CI 0.29–0.75). RBS may be useful to stratify the infection risk: a strict collaboration between surgeons and infectious disease specialists is needed to implement source control and antimicrobial surveillance.

Coupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients. In this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group). We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose). 39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0-56.0 years; mean burn size 48.0% TBSA, range 35.0-60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221-3.326; p < 0.004) in the multivariate analysis logistic model. CPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT.

Infections caused by multidrug-resistant Gram-negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapy in burn patients in whom pathophysiological changes strongly influence pharmacokinetic (PK) parameters. This study aimed to describe the PK parameters of meropenem in a population of burn patients. Blood samples were collected immediately before and 2 h and 5 h after the start of intravenous drug administration. Plasma meropenem concentrations were determined using an ultra-performance liquid chromatography-photodiode array method. Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for infections byPseudomonas aeruginosa or Acinetobacter baumannii isolated from blood or wounds. Mean Cmax, Cmin, AUC0-24, half-life, drug clearance and volume of distribution were 28.9 mg/L, 3.7 mg/L, 280.2 mg h/L, 2.0 h, 19.0 L/h and 44.4 L, respectively. Six patients (35%) achieved a Cmin ≥3.3 mg/L and seven patients (41%) achieved a Cmax ≥ 28.4 mg/L, whilst nine patients (53%) achieved an AUC0-24 of >226 mg h/L. Given a minimum inhibitory concentration (MIC) of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises to 2 mg/L (the ECOFF), only five patients reached the desired AUC/MIC. Regarding fT>MIC at an MIC of 2 mg/L with a 2-h infusion time, 13 patients (76%) achieved the PK target (>75%). These data suggest that a combined 2-h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.

Sepsis is the leading cause of mortality in patients with burn injuries and it may represent, in these patients, a real diagnostic challenge. Here we studied the profile of miRNAs contained in extracellular vesicles (EVs) (EV-miRNAs) isolated from plasma from burn patients complicated by sepsis at admission and 7 days later. We enrolled 28 burn patients, 18 with (Burn Septic Patients—BSPs) and 10 without (Burn non-Septic Patients—BnSPs) sepsis. Ten healthy subjects (HSs) were used as additional controls. After EV isolation by charge precipitation and miRNA extraction, we proceeded with a two-phase approach. Through a first screening phase, we identified 178 miRNAs differentially expressed in BSPs compared to HSs. Among these, by a validation phase based on qRT-PCR, we found that miR-483-5p, miR-193a-5p, and miR-188-3p were increased in the BSPs compared to the BnSPs and HSs. Upon ROC analysis, all three miRNAs showed a good accuracy in differentiating BSPs from BnSPs, especially miR-483-5p (AUC = 0.955, p-value = 0.001). Moreover, we found 173 miRNAs differentially expressed in BSPs after 7 days from enrollment compared to T0, among whose miR-1-3p, miR-34a-3p, and miR-193a-5p decreased in BSPs after 7 days, in parallel with a decrease in SOFA scores. Finally, the other two miRNAs, miR-34a-3p and miR-193a-5p, positively correlated with the SOFA score. In conclusion, we identified several miRNAs—namely miR-483-5p, miR-193a-5p, and miR-188-3p—with potential clinical utility as diagnostic biomarkers in a heterogeneous population of burn patients at high risk of developing sepsis. Moreover, we found some miRNAs (miR-1-3p, miR-34a-3p, and miR-193a-5p) that vary according to the course of sepsis and others (miR-34a-3p and miR-193a-5p) that are associated with its clinical severity.

Background/Objectives: Quorum Sensing (QS) refers to the communication mechanism in bacterial cells, which occurs through the production and detection of small signaling molecules to coordinate activities and monitor population size. In Gram-negative bacteria, QS is typically mediated by N-acyl-homoserine lactones (HSLs) and 2-alkyl-4(1H)-quinolone metabolites (AQ). The present study aims to develop and validate an LC-MS/MS method for detecting QS molecules and apply it to the analysis of plasma samples from burn patients with septic shock caused by Acinetobacter baumannii. Methods: The LC-MS/MS method was developed and fully validated for the quantitative, simultaneous determination of five HSLs and four AQ molecules, ultimately derived from the plasma of three patients with septic shock, with samples collected over three consecutive days. Results: The developed method proved to be both specific and selective, demonstrating a good fit and linearity over the entire range of interest. Trueness and accuracy were satisfactory. The method showed excellent intra-assay precision (CV% was lower than 15%) and limits of quantification (LOQ) ranging from 0.02 to 0.79 ng/mL. In the patients’ samples, the concentration of 3-OH-C12-HSL peaked at 1.5 ng/mL on the first day, and C7-PQS, C9-PQS, HHQ, and HQNO ranged from 0.5 to 1.5 ng/mL, peaking at 5 ng/mL in one patient on the third day. Conclusions: A method for the simultaneous determination of nine QS molecules by LC-MS/MS was developed and validated. When applied, it showed good performance for the analysis of plasma samples and could be a useful tool for an improvement in the diagnosis, prognosis, or treatment monitoring of infections in burn patients caused by Acinetobacter baumannii.

Objectives: The multidrug-resistant gram-negative (MDRGN) bacterial infections remain the leading cause of mortality in burn patients which are c |