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.

Background Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia. Patients and methods This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality. Results A total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9–56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5–36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes. Conclusions Implementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.

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OBJECTIVE Vancomycin is often empirically used in the management of head and neck infections (HNIs) in children. The objective of this study was to determine the utility of Staphylococcus aureus (SA) nasal PCR to facilitate de-escalation of vancomycin for pediatric HNIs. METHODS This was a single-center, retrospective cohort study of pediatric patients who received empiric intravenous vancomycin for a diagnosis of HNIs between January 2010 and December 2019. Subjects were excluded if they met any of the following: confirmed/suspected coinfection of another site, dialysis, immunocompromised status, admission to the NICU, alternative diagnosis that did not require antibiotics, or readmission for HNIs within 30 days of previous admission. The primary outcome was time to de-escalation of vancomycin. Total duration of antibiotics, treatment failure, hospital length of stay (LOS), and incidence of acute kidney injury (AKI) were also assessed. RESULTS Of the 575 patients identified, 124 patients received an SA nasal PCR. The median time to de-escalation was 39.5 hours in those patients compared with 53.7 hours in patients who did not have a SA nasal PCR (p = 0.002). No difference was noted in total duration of all methicillin-resistant Staphylococcus aureus antibiotics, hospital LOS, treatment failure, and AKI. CONCLUSIONS In a large cohort of pediatric patients with HNIs, those who underwent testing with an SA nasal PCR spent less time receiving intravenous vancomycin, although their LOS was not significantly reduced. Further investigation is needed to better define the role of SA nasal PCRs in determining antibiotic therapy for HNIs.

Background:The consequences of inappropriate antimicrobial use including resistance are increasingly recognized as a global public health threat and many steps have been taken over the last few decades to advance antimicrobial stewardship initiatives with most organ transplant centers currently part of institutions with active antimicrobial stewardship programs.Methods: A review of the literature was conducted and articles were categorized according to the topic and relevance in the judgment of the two authors.Results: A summary review of the currently available literature was created with a focus on periprocedural and outpatient antimicrobial stewardship. Limitations in the data were significant and discussed in the review. Conclusion:The principles of antimicrobial stewardship remain important throughout all phases starting with periprocedural prophylactic antimicrobial selection all the way through to discharge and subsequent healthcare encounters. Despite the broad advances in stewardship initiatives and the rapidly progressing supportive data overall there continue to be significant opportunities for additional research within various special patient populations including recipients of solid organ transplantation (SOT).The recent white paper published in the American Journal of Transplantation called to action the transplant and stewardship communities to have an increased focus and awareness of the issues that antimicrobial overuse can present in the SOT patient population. This is an important step that will hopefully generate more data in this group of patients that arguably faces the greatest vulnerability to the consequences of increased antimicrobial resistance.

BackgroundAccelerate Pheno® (AP) is a novel diagnostic system that provides rapid identification and antibiotic susceptibility results for most commonly isolated organisms within hours of blood culture (BC) positivity. There are little data on this technology’s real-world implementation with antimicrobial stewardship intervention and effect on optimal targeted therapy.MethodsAP was implemented at UIHC in September 2018 and paired with antimicrobial stewardship team (AST) review. AST recommendations were provided in real time during weekday hours and through a retrospective review process for off-hours results. Microbiologic and clinical data were collected prospectively. Due to inconsistencies in instrument performance identified after the first month, two post-implementation periods (Group A = October 2018–January 2019; Group B = February 2019–mid-April 2019) were analyzed to assess quality improvement efforts during clinical roll-out.ResultsIn the 6.5-month combined period, 690 unique BC samples were run on AP and reviewed by AST (417 in A; 273 in B). Performance of the technology improved, with 78.9% (329/417) of isolates in Grp A identified vs. 85.3% in Grp B (233/273). Percentage of runs with progression to antibiotic susceptibility improved from 76.1% to 92.3%. Over both time periods, AST intervened on 277 samples (Figure 1). Recommendations (bug-drug mismatch, de-escalation, dose optimization, and infectious disease consult) were accepted at a rate of 97.4%. Time from BC positivity to optimal therapy was 15.3 hours (Figure 2).ConclusionImplementation of AP with AST review resulted in rapid identification and antibiotic susceptibility results with early optimization of antimicrobial therapy. Highest impact was seen in the management of patients with resistant Gram-negative infections. Oversight of the implementation by a partnership of clinical microbiology and the antimicrobial stewardship team was critical in identifying real-time implementation issues and opportunities for quality improvement. Though real-world performance was slightly inferior to published trial data, the instrument’s exceedingly fast time to AS represents a significant advantage over other systems and enhances clinical care and patient safety particularly when paired with AST intervention. Disclosures All authors: No reported disclosures.