Critically ill patients with community-onset intraabdominal infections: Influence of healthcare exposure on resistance rates and mortality.

The concept of healthcare-associated infections (as opposed to hospital-acquired infections) in intraabdominal infections (IAIs) is scarcely supported by data in the literature. The aim of the present study was to analyse community-onset IAIs (non-postoperative/non-nosocomial) in patients admitted to intensive care units (ICUs), to investigate differences in resistance patterns linked to healthcare exposure and mortality-associated factors. A one-year prospective observational study (17 Spanish ICUs) was performed distributing cases as healthcare-associated infections (HCAI), community-acquired infections (CAI) and immunocompromised patients (ICP). Bacteria producing extended-spectrum ß-lactamases (ESBL) and/or carbapenemase (CPE), high-level aminoglycoside- and/or methicillin- and/or vancomycin- resistance were considered antimicrobial resistant (AMR). Mortality-associated factors were identified by regression multivariate analysis. Of 345 patients included (18.8% HCAI, 6.1% ICP, 75.1% CAI), 51.6% presented generalized peritonitis; 32.5% were >75 years (55.4% among HCAI). Overall, 11.0% cases presented AMR (7.0% ESBL- and/or CPE), being significantly higher in HCAI (35.4%) vs. CAI (5.8%) (p<0.001) vs. ICP (0%) (p = 0.003). Overall 30-day mortality was 14.5%: 23.1% for HCAI and 11.6% for CAI (p = 0.016). Mortality (R2 = 0.262, p = 0.021) was positively associated with age >75 years (OR = 6.67, 95%CI = 2.56-17.36,p<0.001), Candida isolation (OR = 3.05, 95%CI = 1.18-7.87,p = 0.022), and SAPS II (per-point, OR = 1.08, 95%CI = 1.05-1.11, p<0.001) and negatively with biliary infections (OR = 0.06, 95%CI = 0.01-0.48,p = 0.008). In this study, the antimicrobial susceptibility pattern of bacteria isolated from patients with healthcare contact was shifted to resistance, suggesting the need for consideration of the healthcare category (not including hospital-acquired infections) for severe IAIs. 30-day mortality was positively related with age >75 years, severity and Candida isolation but not with AMR.

Melatonin, clock genes and mitochondria in sepsis.

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1ß and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.