In the skin, aging is associated with overall epidermal thinning, decreased barrier function, and gradual deterioration of the epidermal immune response. However, the presence and role of cytokines, chemokines, and biologic analytes (CCBAs) in immunosenescence are not known. Here we identified age-related changes in skin properties and CCBAs from stratum corneum of healthy human subjects, providing a means to utilize CCBAs as benchmarks for aging skin health. Transepidermal water loss and a(*) (skin redness) decreased in an age-dependent manner, and were significantly lower (p < 0.05) in Groups 2 (56.6 ± 4.6 years) and 3 (72.9 ± 3.0 years) vs. Group 1 (24.3 ± 2.8 years). In skin wash fluid, 48 CCBAs were detected; seven were significantly lower (p < 0.05) in Groups 2 and 3: EGF, FGF-2, IFNα2, IL-1RA, HSA, keratin-6, and involucrin; cortisol was significantly higher (p < 0.05) in Groups 2 and 3. Our results correspond with the pro-inflammatory shift that occurs with immunosenescence and also provides basis for understanding the inflammatory changes in normal aging skin.

Background Bloodstream infections (BSI) are a leading cause of morbidity and mortality in hospitalized patients. The IOAS (Improving Outcomes and Antimicrobial Stewardship) study seeks to evaluate the impact of the Accelerate PhenoTest® BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. Methods This multicenter, quasi-experimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX testing, to evaluate the impact this technology has on patients with BSI. Laboratory and clinical data from hospitalized patients with BSI (excluding contaminants) were compared between two arms, one that underwent testing on AXDX (post-AXDX) and one that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) within 96 hours of blood culture positivity and 30-day mortality. Results A total of 854 patients with BSI (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared to the pre-AXDX arm (40.9 hours; P&lt;0.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 versus 13.9 hours; P&lt;0.0001) and first antimicrobial de-escalation (36.0 versus 27.2 hours; P=0.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX versus 6.0% post-AXDX), length of stay (7.0 pre-AXDX versus 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 versus 6.4 days; P=0.03) among patients with Gram-negative bacteremia. Conclusions For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial de-escalation.

Background Days of Therapy (DOT), the most widely used benchmarking metric for antibiotic consumption, may not fully measure stewardship efforts to promote use of narrow-spectrum agents and may inadvertently discourage the use of combination regimens when single-agent alternatives have greater adverse effects. To overcome DOT’s limitations, we developed a novel metric, Days of Antibiotic Spectrum Coverage (DASC), and compared hospitals’ performances using this novel metric with DOT. Methods We evaluated 77 antibiotics in 16 categories of antibacterial activity to develop our spectrum scoring system. DASC was then calculated as cumulative daily spectrum scores. To compare hospital benchmarking using DOT and DASC, we conducted a retrospective cohort study of adult patients admitted to acute care units within the Veterans Health Administration system in 2018. Antibiotic administration data were aggregated to calculate each hospital’s DOT and DASC per 1,000 days present (DP) for ranking. Results The spectrum score for each antibiotic ranged from 2 to 15. There was little correlation between DOT per 1,000 DP and DASC per DOT, indicating that lower antibiotic consumption at a hospital does not necessarily mean more frequent use of narrow-spectrum antibiotics. The differences in each hospital’s ranking between DOT and DASC per 1,000 DP ranged from -29.0% to 25.0%, respectively, with 27 (21.8%) hospitals having differences &gt;10%. Conclusions We propose a novel composite metric for antibiotic stewardship, DASC, that combines consumption and spectrum as a potential replacement for DOT. Further studies are needed to evaluate whether benchmarking using the DASC will improve evaluations of stewardship.

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