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Julie Ann Justo, P Brandon Bookstaver Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic acid), timing of initiation and therapy duration, optimal dwell time and catheter accessibility, and risks of ALT are also described. Development of local protocols is recommended in order to avoid these potential barriers and encourage utilization of ALT where appropriate. Keywords: antibiotic lock, biofilm, bacteremia, catheter-related bloodstream infection

Chenopodium quinoa Willd (quinoa) has acquired an increased agronomical and nutritional relevance due to the capacity of adaptation to different environments and the exceptional nutritional properties of their seeds. These include high mineral and protein contents, a balanced amino acid composition, an elevated antioxidant capacity related to the high phenol content, and the absence of gluten. Although it is known that these properties can be determined by the environment, limited efforts have been made to determine the exact changes occurring at a nutritional level under changing environmental conditions in this crop. To shed light on this, this study aimed at characterizing variations in nutritional-related parameters associated with the year of cultivation and different genotypes. Various nutritional and physiological traits were analyzed in seeds of different quinoa cultivars grown in the field during three consecutive years. We found differences among cultivars for most of the nutritional parameters analyzed. It was observed that the year of cultivation was a determinant factor in every parameter studied, being 2018 the year with lower yields, germination rates, and antioxidant capacity, but higher seed weights and seed protein contents. Overall, this work will greatly contribute to increase our knowledge of the impact of the environment and genotype on the nutritional properties of quinoa seeds, especially in areas that share climatic conditions to Southern Europe.

Twelve high-quality chia protein hydrolysates (CPHs) were produced from chia protein isolate (CPI) in a pilot plant of vegetable proteins. To obtain functional hydrolysate, four CPHs were hydrolyzed by the action of Alcalase, an endoprotease, and the other eight CPHs were hydrolyzed by the action of Flavourzyme, an exoprotease. Alcalase-obtained CPHs showed significant antihypertensive properties particularly, the CPH obtained after 15 min of hydrolysis with Alcalase (CPH15A), which showed a 36.2% hydrolysis degree. In addition, CPH15A increased the antioxidant capacity compared to CPI. The CPH15A physicochemical composition was characterized and compared to chia defatted flour (CDF) and CPI, and its techno-functional properties were determined by in vitro experiments through the analysis of its oil absorption capacity, as well as the capacity and stability of foaming and emulsifying, resulting in an emulsifier and stabilizer better than the intact protein. Therefore, the present study revealed that CPH15A has potent antihypertensive and antioxidant properties and can constitute an effective alternative to other plant protein ingredients sources that are being used in the food industry.

Background: The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap., Methods: We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed., Results: Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features., Conclusions: Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula., Competing Interests: Potential conflicts of interest. A. Y. K. has received research funding from Paratek Pharmaceuticals and American College of Clinical Pharmacy. G. F. has received funding from Critical Innovations, LLC, and grant funding from Melinta Therapeutics. K. C. has received research grants from the National Institutes of Health, Biomedical Advanced Research and Development Authority, and Merck and panel discussion honorarium from Ferring. E. J. S. has received research funding from Merck and bioMérieux. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document., Methods: A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States., Results: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults., Conclusions: The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Local institutional guidelines and order sets were updated in June 2023 to recommend first-line cefoxitin monotherapy for the treatment of intra-amniotic infections (IAIs) and endometritis. This study evaluated the clinical impact of this change., Methods: This was a retrospective, observational cohort study in an 11-campus health system comparing clinical outcomes of patients with chorioamnionitis, endometritis, or septic abortion receiving intravenous antimicrobial therapy before and after implementation of first-line cefoxitin monotherapy recommendations for the treatment of these infections. Primary outcome was a composite of serious clinical events postdelivery (ie, intensive care unit admission, death, hospital readmission related to IAI or endometritis within 30 days, additional surgery or procedures, or deep surgical site infection). Baseline characteristics between the pre- and post-cefoxitin groups were compared via Student's t tests for continuous variables and chi-square tests for categorical variables. Outcomes were evaluated via generalized linear modeling., Results: A total of 472 patients were enrolled, 350 (74%) in the pre-cefoxitin group and 122 (26%) in the post-cefoxitin group. Groups were significantly different by race, healthcare payor, and hospital campus. Cefoxitin was rarely used in the pre-cefoxitin group (n = 2, <0.1%) and commonly used in the post-cefoxitin group (n = 112, 91.8%). After controlling for group differences, odds of experiencing serious clinical event postdelivery in the post-cefoxitin group were noninferior to those in the pre-cefoxitin group (adjusted odds ratio, .37; 95% CI, .17-.76; P = .010)., Conclusions: Local institutional guidelines with predominant use of cefoxitin therapy were noninferior to traditional antimicrobial therapy regimens for the treatment of IAI., Competing Interests: Potential conflicts of interest. J. A. J. has served as an advisor for Entasis Therapeutics, Gilead Sciences, and Shionogi. P. B. reports grants Centers for Disease Control and Prevention (CDC-RFA-CK22-2203). A. C. reports grant National Institutes of Health R01HD082311. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: JAJ has received grant funding from the Society of Infectious Diseases Pharmacists for research on Gram-positive bacterial infections. JMP declares no competing interests.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU)., Design: Retrospective, multicenter, cohort., Setting: Ten hospitals in the southeastern United States., Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel β-lactams., Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 ( P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel β-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden., Conclusions: The overall prevalence of GNB with DTR and the use of novel β-lactams remain low. However, the uptrend in the use of novel β-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR., Competing Interests: Potential conflicts of interest. D.C. reports that he is pending a patent with Genus, group, species, and/or strain-specific 16s rdna sequences. B.J. reports that he is the member of the speaker’s bureau for Abbie, Paratek, Innoviva, and Ferring. M.A. reports that he serves on IDSA Antimicrobial Resistance Committee, International Working Group for Diabetic Foot Infection Guideline Panel, and WHO Antimicrobial Resistance Expert Group on Human Health Research. P.B. reports that she has two ongoing grants (CDC-RFA-CK22-2203 and University of South Carolina Center for Rural and Primary Healthcare). J.A.J. reports that she is on the advisory board for Entasis Therapeutics and Shionogi. Potential conflicts of interest. All other authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Ending the human immunodeficiency virus (HIV) epidemic relies on a robust clinical workforce. The Southeast AIDS Education and Training Center's interprofessional education program is a novel approach to increasing the interest and ability of early health professional learners to provide high-quality, comprehensive, person-first care for people with HIV. Key Points: Interprofessional education (IPE) focusing on multidisciplinary care for people with HIV can serve as a novel way to increase the HIV workforce. This brief report describes the IPE program of the Southeast AIDS Education and Training Center., Competing Interests: Potential conflicts of interest. J. A. J. has served on the advisory boards for Entasis Therapeutics, Gilead Sciences, and Shionogi and has served as a speaker for Spero Therapeutics. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Inpatient antimicrobial stewardship (AS) programs are quality improvement programs tasked with improving antibiotic practices by augmenting frontline providers' antibiotic prescription. Prospective audit and feedback (PAF) and preauthorization (PRA) are essential activities in the hospital that can be resource intensive for AS teams. Improving efficiency in AS activities is needed when there are limited resources or when programs are looking to expand tasks beyond PAF and PRA, such as broad education or guideline development. Guidance on the creation and maintenance of alerts for the purpose of PAF reviews, modifications of antibiotic restrictions for PRA polices, and overall initiative prioritization strategies are reviewed. In addition, daily prioritization tools, such as the tiered approach, scoring systems, and regression modeling, are available for stewards to prioritize their daily workflow. Using these tools and guidance, AS programs can be productive and impactful in the face of resource limitation or competing priorities in the hospital., Competing Interests: Potential conflicts of interest. J. J. receives payment for lectures from bioMérieux and Spero Therapeutics and participates in Merck, Entasis Therapeutics, Shionogi, and Gilead Sciences advisory boards. E. L. H. receives consulting fees from Wolters-Kluwer/Lexi-Comp. J. T. B. reports no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Clinical tools for the prediction of antimicrobial resistance have been derived and validated without examination of their implementation in clinical practice. This study examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on the time to initiation of appropriate antimicrobial therapy for bloodstream infection (BSI). The quasi-experimental cohort study included hospitalized adults with BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales at three community hospitals in Columbia, South Carolina, USA before (January 2010 to December 2013) and after (January 2014 to December 2019) implementation of an antimicrobial stewardship intervention. In total, 45 and 101 patients with BSI due to CRO-R Enterobacterales were included before and after the intervention, respectively. Overall, the median age was 66 years, 85 (58%) were men, and 86 (59%) had a urinary source of infection. The mean time to appropriate antimicrobial therapy was 78 h before and 46 h after implementation of the antimicrobial stewardship intervention ( p = 0.04). Application of the ESBL prediction score as part of an antimicrobial stewardship intervention was associated with a significant reduction in time to appropriate antimicrobial therapy in patients with BSI due to CRO-R Enterobacterales . Utilization of advanced rapid diagnostics may be necessary for a further reduction in time to appropriate antimicrobial therapy in this population.

Using the visibility graph algorithm (VGA), a complex network can be associated with a time series, such that the properties of the time series can be obtained by studying those of the network. Any value of the time series becomes a node of the network, and the number of other nodes that it is connected to can be quantified. The degree of connectivity of a node is positively correlated with its magnitude. The slope of the regression line is denoted by k-M , and, in this work, this parameter was calculated for the cardiac interbeat time series of different contrasting groups, namely: young vs. elderly; healthy subjects vs. patients with congestive heart failure (CHF); young subjects and adults at rest vs. exercising young subjects and adults; and, finally, sedentary young subjects and adults vs. active young subjects and adults. In addition, other network parameters, including the average degree and the average path length, of these time series networks were also analyzed. Significant differences were observed in the k-M parameter, average degree, and average path length for all analyzed groups. This methodology based on the analysis of the three mentioned parameters of complex networks has the advantage that such parameters are very easy to calculate, and it is useful to classify heartbeat time series of subjects with CHF vs. healthy subjects, and also for young vs. elderly subjects and sedentary vs. active subjects.

Nontuberculous mycobacterial (NTM) infections present a treatment challenge for clinicians and patients. There are limited data about current susceptibility patterns and treatment outcomes in U.S. adults. This was a 10-year, single-center, retrospective, observational cohort study of adults with a positive NTM culture and clinical suspicion of infection between 1 January 2010 and 30 June 2020. The primary objective was to identify predictors for favorable treatment outcomes. Key secondary objectives were characterization of NTM epidemiology, susceptibility profiles, and safety and tolerability of treatment, including the proportion of subjects with an antimicrobial change and the reasons for the change. Of 250 subjects diagnosed with NTM infection, the most prevalent NTM isolates were Mycobacterium avium intracellulare complex (66.8%) followed by Mycobacterium abscessus (17.6%). Antimicrobial susceptibility data were available for 52.4% of the cohort (45.8% slow growers; 54.2% rapid growers). Only 88 (35%) subjects received treatment with evaluable clinical outcomes. The proportion of subjects with a favorable outcome was 61.4%. More subjects in the unfavorable outcome group experienced a change in antimicrobial therapy (73.5% vs. 51.9%, p = 0.043). The most common reason for antimicrobial change was adverse drug events ( n = 36, 67.9%). In the regression model, private insurance was associated with a favorable outcome, whereas having multiple antimicrobial changes was associated with an unfavorable outcome. The complexity of NTM treatment and high incidence of medication-related issues suggest the necessity of interdisciplinary collaboration to improve overall treatment outcomes in NTM infections.

Purpose: Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72-96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI., Methods: Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination., Results: Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2-2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4-10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001)., Conclusion: ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The Antimicrobial Stewardship Collaborative of South Carolina created quarterly Comparative SAAR Analysis Reports based on standardized antimicrobial administration ratio (SAAR) data from the NHSN Antimicrobial Use (AU) Option. These reports provide SAAR histograms and site-specific feedback to participating facilities in South Carolina. They were created to improve antimicrobial use throughout the state, especially in rural regions., (© The Author(s) 2022.)

Clinicians, researchers, and the public frequently turn to digital channels and social media for up-to-the-minute information on novel therapeutics and vaccines. The value of credible infectious diseases drug information is more apparent in the setting of the coronavirus disease 2019 (COVID-19) pandemic. This viewpoint by the Society of Infectious Diseases Pharmacists (SIDP) provides guidance on utilizing social media platforms to optimize infectious diseases pharmacotherapy. It includes tips for all levels of users but primarily serves a guide for the infectious diseases clinician who has not yet joined social media. It compares various social media platforms and suggests which to begin with based on user needs, recommends efficient curation of social media content, and outlines a stepwise approach (shown below) to increasing engagement over time. This summary will hopefully spur further quality content and engagement regarding drug information from the infectious diseases social media network., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact., Methods: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum")., Results: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning., Conclusions: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: The quick Pitt bacteremia score (qPitt) predicts mortality in patients with serious infections due to gram-negative bacteria. This retrospective cohort study examines utility of qPitt to predict mortality in patients with Staphylococcus aureus bloodstream infection (SAB)., Methods: Multivariate logistic regression was used to examine risk factors for 28-day mortality in hospitalized adults with SAB at four Prisma Health hospitals in South Carolina, USA from January 2015 to December 2017. Area under receiver operating characteristic curve (AUROC) was used to examine model discrimination., Results: Among 692 patients with SAB, 305 (44%) had methicillin-resistant S. aureus (MRSA), and 129 (19%) died within 28 days. After adjustment for age, comorbidities, and MRSA, each component of the qPitt was associated with 28-day mortality. There was a 3-fold increase in the risk of 28-day mortality for each one-point increase in qPitt. Predicted 28-day mortality was 3%, 9%, 22%, 45%, and 70% for qPitt of 0, 1, 2, 3, and ≥4, respectively. AUROC of the qPitt in predicting 28-day, 14-day, and in-hospital mortality were 0.80, 0.81, and 0.80, respectively., Conclusions: The qPitt predicts mortality with good discrimination in SAB. These results support using qPitt as a measure of acute severity of illness in future studies., Competing Interests: Decllaration of Competing Interest JAJ: bioMérieux, Speaker's Bureau (nonbranded content), Merck, Advisory Board; PBB: bioMérieux, Speaker's Bureau (nonbranded content), Kedrion Biopharma Advisory Board, research grant; all other authors: no conflicts., (Copyright © 2021. Published by Elsevier Ltd.)

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. There was no difference in clinical failure between the two cohorts (22% vs. 30%; p = 0.491). Six patients in the SOC cohort left against medical advice (AMA) prior to completing therapy. Among those who did not leave AMA, receipt of LaLGPs resulted in a decreased hospital length of stay by an average of 13.6 days. The average total healthcare-related cost of care was USD 295,589 in the LaLGP cohort compared to USD 326,089 in the SOC cohort ( p = 0.282). Receipt of LaLGPs may be a beneficial treatment option for patients with deep-seated infections and socioeconomic factors who are not candidates for oral transition or OPAT.

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: This retrospective cohort study examined the impact of the pandemic on antimicrobial use (AU) in South Carolina hospitals., Methods: Antimicrobial use in days of therapy (DOT) per 1000 days-present was evaluated in 17 hospitals in South Carolina. Matched-pairs mean difference was used to compare AU during the pandemic (March-June 2020) with that during the same months in 2019 in hospitals that did and did not admit patients with COVID-19., Results: There was a 6.6% increase in overall AU in the seven hospitals that admitted patients with COVID-19 (from 530.9 to 565.8; mean difference (MD) 34.9 DOT/1000 days-present; 95% CI 4.3, 65.6; P = 0.03). There was no significant change in overall AU in the remaining 10 hospitals that did not admit patients with COVID-19 (MD 6.0 DOT/1000 days-present; 95% CI -55.5, 67.6; P = 0.83). Most of the increase in AU in the seven hospitals that admitted patients with COVID-19 was observed in broad-spectrum antimicrobial agents. A 16.4% increase was observed in agents predominantly used for hospital-onset infections (from 122.3 to 142.5; MD 20.1 DOT/1000 days-present; 95% CI 11.1, 29.1; P = 0.002). There was also a 9.9% increase in the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents (from 66.7 to 73.3; MD 6.6 DOT/1000 days-present; 95% CI 2.3, 10.8; P = 0.01)., Conclusion: The COVID-19 pandemic appears to drive overall and broad-spectrum antimicrobial use in South Carolina hospitals admitting patients with COVID-19. Additional antimicrobial stewardship resources are needed to curtail excessive antimicrobial use in hospitals to prevent subsequent increases in antimicrobial resistance and Clostridioides difficile infection rates, given the continuing nature of the pandemic., Competing Interests: Declarations of Competing Interests PB, JK, CMF, SU, EL, LS, SW, and MNA: no conflicts HRW: bioMérieux, Speaker's Bureau (nonbranded content); JJ: bioMérieux, Speaker's Bureau (nonbranded content), Merck, Advisory Board; PBB: bioMérieux, Speaker's Bureau (nonbranded content), Kedrion Biopharma Advisory Board, research grant., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In this cross-sectional population-based study, women had significantly higher crude incidence rates of both community-associated Clostridioides difficile infection (CA-CDI) and ambulatory antibiotic prescriptions compared to men in South Carolina in 2015. After adjustments for antibiotic prescription rates, there was no difference in the incidence rates of CA-CDI between the genders.

Background: The role of follow up blood cultures (FUBC) in the management of gram-negative bloodstream infection (GN-BSI) remains controversial. This retrospective cohort study examines the association between obtaining FUBC and mortality in GN-BSI., Methods: Hospitalized adults with community-onset GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from January 1, 2010 to June 30, 2015 were identified. Patients who died or were discharged from hospital within 72 h were excluded to minimize impact of survival and selection biases on results, respectively. Multivariate Cox proportional hazards regression was used to examine association between obtaining FUBC and 28-day all-cause mortality after adjustment for the propensity to obtain FUBC., Findings: Among 766 patients with GN-BSI, 219 (28.6%) had FUBC obtained and 15 of 219 (6.8%) FUBC were persistently positive. Overall, median age was 67 years, 438 (57%) were women, 457 (60%) had urinary source of infection, and 426 (56%) had BSI due to Escherichia coli . Mortality was significantly lower in patients who had FUBC obtained than in those who did not have FUBC (6.3% vs. 11.7%, log-rank p  = 0.03). Obtaining FUBC was independently associated with reduced mortality (hazards ratio 0.47, 95% confidence intervals: 0.23-0.87; p =  0.02) after adjustments for age, chronic comorbidities, acute severity of illness, appropriateness of empirical antimicrobial therapy, and propensity to obtain FUBC., Interpretation: Improved survival in hospitalized patients with GN-BSI who had FUBC is consistent with the results of recent publications from Italy and North Carolina supporting utilization of FUBC in management of GN-BSI., Funding: This study had no funding source., Competing Interests: RA, JK, and MNA: no conflicts HRW: bioMérieux, Speaker's Bureau (outside the submitted work); JJ: bioMérieux, Speaker's Bureau, Merck, Advisory Board (outside the submitted work); PBB: bioMérieux, Speaker's Bureau, Kedrion Biopharma, Advisory Board, research grant (outside the submitted work)., (© 2021 The Author(s).)

The standardized antimicrobial administration ratio (SAAR) is a novel antimicrobial stewardship metric that compares actual to expected antimicrobial use (AU). This prospective cohort study examines the utility of SAAR reporting and inter-facility comparisons as a motivational tool to improve overall and broad-spectrum AU within a three-hospital healthcare system. Transparent inter-facility comparisons were deployed during system-wide antimicrobial stewardship meetings beginning in October 2017. Stakeholders were advised to interpret the results to foster competition and incorporate SAAR data into focused antimicrobial stewardship interventions. Student's t -test was used to compare mean SAARs in the pre- (July 2017 through October 2017) and post-intervention periods (November 2017 through June 2019). The mean pre-intervention SAARs for hospitals A, B, and C were 0.69, 1.09, and 0.60, respectively. Hospital B experienced significant reductions in SAAR for overall AU (from 1.09 to 0.83; p < 0.001), broad-spectrum antimicrobials used for hospital-onset infections (from 1.36 to 0.81; p < 0.001), and agents used for resistant gram-positive infections in the intensive care units (from 1.27 to 0.72; p < 0.001) after the interventions. The alignment of the SAAR across the health-system and sustained reduction in overall and broad-spectrum AU through implementation of inter-facility comparisons demonstrate the utility in the motivational application of this antimicrobial use metric.

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus β-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T >MIC ). This was a single-centre retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting. Safety and effectiveness were assessed. When therapeutic drug monitoring (TDM) was performed, area under the concentration-time curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. CI C/T was used in seven unique regimens over the 31-month evaluation period. Patient age ranged from 23-70 years and the indication was primarily for treatment of deep-seated infections caused by multidrug-resistant Pseudomonas aeruginosa. Four regimens (57%) were used for outpatient transitions of care. The typical dose was 6 g every 24 h, although a renally adjusted dose was used in two instances (29%). TDM was performed in four uses (57%) and target attainment was confirmed in each. Ceftolozane AUC ranged from 365.7-818.2 μg•(h/mL). All patients had positive outcomes with no significant adverse events. One patient developed acute gout flares. One patient had recurrent infection with C/T-resistant P. aeruginosa after ~3 months of reduced dose for suppression. CI C/T was successfully utilised for deep-seated infections in inpatient and outpatient settings. TDM confirmed that CI C/T achieved pharmacodynamic targets for the entire dosing interval, suggesting an effective alternative dosing regimen applicable across the continuum of care., (Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objective: This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital., Methods: All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.g. Clostridioides difficile PCR), or laxative use in the preceding 48 h. Antibiotic use and host variables were compared between groups with positive and negative results., Results: During the study period, 442 GI panels were obtained, among which 268 (61%) were deemed inappropriate. Primary reasons for inappropriate testing were lack of documented diarrhea ( n  = 92), greater than 2 days of hospitalization ( n  = 116), having a duplicate C. difficile PCR test ordered ( n  = 118), or laxative use in the 48 h before testing ( n  = 36). A total of 141 (32%) GI panels were positive. The most frequently identified pathogens were C. difficile (51.1%, n  = 72), Enteropathogenic Escherichia coli (17.7%, n  = 25), and Norovirus GI/GII (12.1%, n  = 17). Patients with negative GI panel results were initiated on antibiotics significantly less frequently than those with positive GI panels (62.5% versus 80.2%, p  < 0.00001)., Conclusion: Stewardship opportunities exist to optimize the diagnostic application of the GI multiplex PCR panel., Competing Interests: Conflict of interest statement: Julie Ann Justo: bioMérieux Speaker’s Bureau (non-branded content). P. Brandon Bookstaver: bioMérieux Speaker’s Bureau (non-branded content). All other authors have no conflicts of interest., (© The Author(s), 2020.)

Objectives: Increasing antimicrobial resistance rates limit empirical antimicrobial treatment options for Gram-negative bloodstream infections (GN-BSI). However, antimicrobial resistance may be predicted based on patient-specific risk factors using precision medicine concepts. This retrospective, 1:2 matched cohort examined clinical outcomes in hospitalized adults without major risk factors for antimicrobial resistance receiving empirical fluoroquinolones or broad-spectrum beta-lactams (BSBL) for GN-BSI at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 2010 through June 2015., Methods: Multivariable logistic regression was used to examine early treatment failure at 72-96 h from GN-BSI. Cox proportional hazards regression was used to examine 28-day mortality and hospital length of stay (HLOS)., Results: Among 74 and 148 patients receiving empirical fluoroquinolones and BSBL for GN-BSI, respectively, median age was 68 years, 159 (72%) were women, and 152 (68%) had a urinary source of infection. Early treatment failure rates were comparable in fluoroquinolone and BSBL groups (27% vs. 30%, respectively, odds ratio 0.82, 95% confidence intervals [CI] 0.43-1.54, P = 0.53), as well as 28-day mortality (8.9% vs. 9.7%, respectively, hazards ratio [HR] 0.74, 95% CI 0.26-1.90, P = 0.54). Median HLOS was 6.1 days in the fluoroquinolone group and 7.1 days in the BSBL group (HR 0.73, 95% CI 0.54-0.99, P = 0.04). Transition from intravenous to oral therapy occurred sooner in the fluoroquinolone group than in the BSBL group (3.0 vs. 4.9 days, P < 0.001)., Conclusions: In the absence of antimicrobial resistance risk factors, fluoroquinolones provide an additional empirical treatment option to BSBL for GN-BSI. Shorter HLOS in the fluoroquinolone group may be due to earlier transition from intravenous to oral antimicrobial therapy., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Objective: To examine the temporal trends in ambulatory antibiotic prescription fill rates and to determine the influences of age, gender, and location., Design: Population-based cohort study., Setting: Ambulatory setting in South Carolina., Patients: Patients ≤64 years of age from January 2012 to December 2017., Methods: Aggregated pharmacy claims data for oral antibiotic prescriptions were utilized to estimate community antibiotic prescription rates. Poisson regression or Student t tests were used to examine overall temporal trend in antibiotic prescription rates, seasonal variation, and the trends across age group, gender, and rural versus urban location., Results: Overall antibiotic prescription rates decrease from 1,127 to 897 per 1,000 person years (P < .001). The decrease was more noticeable in persons aged <18 years (26%) and 18-39 years (20%) than in those aged 40-64 years (5%; P < .001 for all). Prescription rates were higher among females than males in all age groups, although this finding was the most pronounced in group aged 18-39 years (1,232 vs 585 per 1,000 person years; P < .0001). Annualized antibiotic prescription rates were higher during the winter months (December-March) than the rest of the year (1,145 vs 885 per 1,000 person years; P < .0001), and rates were higher in rural areas than in urban areas (1,032 vs 941 per 1,000 person years; P < .0001)., Conclusions: The decline in ambulatory antibiotic prescription rates is encouraging. Ongoing ambulatory antibiotic stewardship efforts across South Carolina should focus on older adults, rural areas, and during the winter season when antibiotic prescriptions peak.

Objectives: This study aimed to predict trimethoprim/sulfamethoxazole (SXT) resistance in patients with community-onset urinary tract infection (UTI) due to Enterobacteriaceae based on patient-specific risk factors., Methods: This was a retrospective case-control study in Prisma Health facilities in central South Carolina, USA, including three community hospitals, affiliated emergency departments and ambulatory clinics, including adult patients with community-onset UTI due to Enterobacteriaceae (1 April 2015 to 29 February 2016). Multivariate logistic regression was used to examine risk factors for SXT resistance., Results: Among 351 unique patients with community-onset UTI, 71 (20.2%) had SXT-resistant Enterobacteriaceae urinary isolates. Overall, median age was 64 years and 252 (71.8%) were female. A multivariate model identified prior urinary infection/colonisation with SXT-resistant Enterobacteriaceae (OR=8.58, 95% CI 3.92-18.81; P<0.001) and SXT use within past 12 months (OR=2.58, 95% CI 1.13-5.89; P=0.02) as predictors of SXT resistance among urinary isolates. Most patients with UTI (285; 81.2%) had no risk factors for SXT resistance. SXT resistance rates increased from 13% in the absence of risk factors to 31% in patients with prior SXT use, 66% in those with prior urinary infection/colonisation with SXT-resistant Enterobacteriaceae and 73% in the presence of both risk factors., Conclusion: SXT resistance in Enterobacteriaceae urinary isolates may be predicted based on prior urine culture results and SXT use within the previous year. Utilisation of a patient-specific antibiogram may allow empirical SXT use in patients with community-onset UTI in the absence of risk factors for resistance., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species., Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection., Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis., Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents., Competing Interests: P.B.B.—Speaker’s Bureau: bioMérieux. C.M.B.—Speaker’s Bureau: Merck Pharmaceuticals. Grant Funding: ALK Abello. S.T.K.—Speaker’s Bureau: Melinta Therapeutics. J.A.J.—Speaker’s Bureau: bioMérieux. All other authors report no potential conflicts of interest.

Expanding pharmacist-driven antimicrobial stewardship efforts in the emergency department (ED) can improve antibiotic management for both admitted and discharged patients. We piloted a pharmacist-driven culture and rapid diagnostic technology (RDT) follow-up program in patients discharged from the ED. This was a single-center, pre- and post-implementation, cohort study examining the impact of a pharmacist-driven culture/RDT follow-up program in the ED. Adult patients discharged from the ED with subsequent positive cultures and/or RDT during the pre- (21 August 2018-18 November 2018) and post-implementation (19 November 2018-15 February 2019) periods were screened for inclusion. The primary endpoints were time from ED discharge to culture/RDT review and completion of follow-up. Secondary endpoints included antimicrobial agent prescribed during outpatient follow-up, repeat ED encounters within 30 days, and hospital admissions within 30 days. Baseline characteristics were analyzed using descriptive statistics. Time-to-event data were analyzed using the Wilcoxon signed-rank test. One-hundred-and-twenty-seven patients were included, 64 in the pre-implementation group and 63 in the post-implementation group. There was a 36.3% reduction in the meantime to culture/RDT data review in the post-implementation group (75.2 h vs. 47.9 h, p < 0.001). There was a significant reduction in fluoroquinolone prescribing in the post-implementation group (18.1% vs. 5.4%, p = 0.036). The proportion of patients who had a repeat ED encounter or hospital admission within 30 days was not significantly different between the pre- and post-implementation groups (15.6 vs. 19.1%, p = 0.78 and 9.4% vs. 7.9%, p = 1.0, respectively). Introduction of a pharmacist culture and RDT follow-up program in the ED reduced time to data review, time to outpatient intervention and outpatient follow-up of fluoroquinolone prescribing.

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: -6.6, -3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD -7.8, 95% CI: -14.6, -1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD -9.3, 95% CI: -16.1, -2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections.

Objectives: This cross-sectional population-based study aims to determine overall incidence rate of Clostridioides difficile infection (CDI) in the State of South Carolina and provide an estimated cost of hospitalization due to community-associated CDI (CA-CDI)., Methods: All CDI cases in South Carolina were identified through National Healthcare Safety Network (NHSN) and the South Carolina Infectious Disease and Outbreak Network (SCION) from January 1, 2015 to June 30, 2016, excluding infants < 1 year of age., Results: During the 18-month study period, 10,254 CDI events were identified in South Carolina residents with an overall incidence rate of 139/100,000 person-years. Over one-half of CDI cases were CA-CDI (5192; 51%) with an incidence rate of 71/100,000 person-years. Among patients with CA-CDI, 2127 (41%) required hospitalization with a median length of stay of 5 days. The annual burden of CA-CDI in South Carolina was estimated to be 9282 hospital days and $16,217,295 in hospitalization costs., Conclusion: The incidence rate of CA-CDI in South Carolina has surpassed both community-onset healthcare facility associated and hospital-onset CDI combined. The heavy burden of CA-CDI justifies dedication of public health resources to combat CDI in ambulatory settings, through antimicrobial stewardship initiatives.

Objectives: The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI)., Methods: Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset)., Results: Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2-2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1-2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4-3.3), altered mental status (aOR 4.5, 95% CI 2.8-7.1), and white blood cell count >12 000/mm 3 (aOR 2.7, 95% CI 1.8-4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively)., Conclusions: Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Antimicrobial use (AU) of antipseudomonal β-lactams (APBL) has significantly increased over the past decade in US hospitals. This retrospective cohort study compares 2 common antimicrobial stewardship strategies, syndrome-specific interventions and antimicrobial postprescription prospective audit and feedback (PAF), in reducing AU of APBL at a large community-teaching hospital., Methods: Four antimicrobial stewardship interventions targeting APBL were serially introduced, including 2 syndrome-specific interventions (bloodstream and intra-abdominal infections) and 2 PAF interventions (carbapenems and piperacillin/tazobactam). Multivariable linear regression was used to examine overall AU of APBL and audited antimicrobial agents., Results: Overall AU of APBL declined from 92.4-69.1 days of therapy (DOT) per 1,000 patient-days between February 2013 and July 2017 (P < .001). Both syndrome-specific interventions were associated with significant reduction in AU of APBL (-7.7 [95% confidence interval (CI): -11.5, -4.0] and -6.0 [95% CI: -9.7, -2.3] DOT per 1,000 patient-days) for bloodstream and intra-abdominal infections, respectively). No significant change in overall AU of APBL was observed after implementation of PAF interventions for carbapenems (-1.4 [95% CI: -7.4, 4.6] DOT per 1,000 patient-days) or piperacillin/tazobactam (0.9 [95% CI: -3.7, 5.4] DOT per 1,000 patient-days)., Conclusions: Implementation of syndrome-specific interventions was followed by significant reduction in AU of APBL in this population. Despite reducing AU of targeted agents, neither PAF intervention contributed to overall observed decline in APBL use, likely due to compensatory increase in using other APBL., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may be appropriately prescribed when necessary for future infections. While allergists have primarily been responsible for PST in the outpatient setting, there is an increasing role for pharmacist involvement in the process. This review highlights the importance of penicillin allergy assessments, considerations for PST in the outpatient setting, education and advocacy for patients and clinicians, and the pharmacist's role in outpatient PST.

The consequences of a documented penicillin allergy in the medical record are especially troublesome in acutely ill, hospitalized patients. A penicillin allergy label may lead to alternative or second line therapies resulting in adverse drug events, negative clinical outcomes and increased costs. Reconciling penicillin allergies is a necessity to facilitate early, optimal therapy and is a shared responsibility among the healthcare team. Penicillin skin testing (PST) has been utilized successfully in hospitalized patients to de-label erroneous penicillin allergies and optimize antibiotic therapy. This targeted review aims to discuss the practical development and implementation of PST in the inpatient setting. This includes a needs assessment checklist with common considerations allowing for customization to one's institution based on available personnel, time, and technological resources.

For decades, the performance of antimicrobial stewardship programs (ASPs) has been measured by incidence rates of hospital-onset Clostridioides difficile and other infections due to multidrug-resistant bacteria. However, these represent indirect and nonspecific ASP metrics. They are often confounded by factors beyond an ASP's control, such as changes in diagnostic testing methods or algorithms and the potential of patient-to-patient transmission. Whereas these metrics remain useful for global assessment of healthcare systems, antimicrobial use represents a direct metric that separates the performance of an ASP from other safety and quality teams within an institution. The evolution of electronic medical records and healthcare informatics has made measurements of antimicrobial use a reality. The US Centers for Disease Control and Prevention's initiative for reporting antimicrobial use and standardized antimicrobial administration ratio in hospitals is highly welcomed. Ultimately, ASPs should be evaluated based on what they do best and what they can control, that is, antimicrobial use within their own institution. This narrative review critically appraises existing stewardship metrics and advocates for adopting antimicrobial use as the primary performance measure. It proposes novel formulas to adjust antimicrobial use based on quality of care and microbiological burden at each institution to allow for meaningful inter-network and inter-facility comparisons.

Currently, gold nanoparticles have found applications in engineering and medical sciences, taking advantage from their properties and characteristics. Surface plasmon resonance, for instance, is one of the main features for optical applications and other physical properties, like high density, that represents the key for cellular uptake. Among other applications, in the medical field, some diseases may be treated by using gene therapy, including monogenetic or polygenetic disorders and infections. Gene adding, suppression, or substitution is one of the many options for genetic manipulation. This work explores an alternative non-viral method for gene transfer by using gold nanoparticles functionalized with organic polymers; two routes of synthesis were used: one of them with sodium borohydride as reducing agent and the other one with chitosan oligosaccharide as reducing and stabilizing agent. Gold nanoparticles conjugated with chitosan, acylated chitosan and chitosan oligosaccharide, were used to evaluate transfection efficiency of plasmid DNA into cell culture (HEK-293). Physical and chemical properties of gold nanocomposites were characterized by using UV-Vis Spectroscopy, ξ-potential, and transmission electron microscopy. Furthermore, the interaction between gold nanoparticles and plasmid DNA was demonstrated by using agarose gel electrophoresis. Transfection tests were performed and evaluated by β-galactosidase activity and green fluorescence protein expression. The percentage of transfection obtained with chitosan, acylated chitosan, and chitosan oligosaccharide were of 27%, 33%, and 60% respectively.

Background: There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal β-lactam (APBL) therapy within 48 hours of Enterobacteriaceae bloodstream infections (BSIs) on 90-day risk of CDI., Methods: Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, South Carolina, from 1 January 2011 through 30 June 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours or ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL., Results: Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs 1.8%; log-rank P = .002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR], 3.56 [95% confidence interval {CI}, 1.48-9.92]; P = .004) and end-stage renal disease (HR, 4.27 [95% CI, 1.89-9.11]; P = .001) were independently associated with higher risk of CDI., Conclusions: The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSIs., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Seasonal variation in community antimicrobial consumption has been demonstrated, with the lowest utilisation rates during summer months. This retrospective cohort study examined seasonality in antimicrobial resistance (AMR) rates of community-acquired Escherichia coli bloodstream isolates. Escherichia coli bloodstream isolates (2010-2015) were identified through the central Palmetto Health microbiology laboratory database. Multivariate logistic regression was used to examine seasonal variation in AMR. Poisson regression was used to evaluate the association between proportion of multidrug-resistant (MDR) isolates and bimonthly ambulatory antimicrobial prescription rates. Among 339 unique patients with community-acquired E. coli bloodstream infection [median age 65 years; 205 (60.5%) female], AMR rates were lower during summer (June-September) than the rest of the year for amoxicillin/clavulanic acid (17% vs. 29%; aOR = 0.53, 95% CI 0.30-0.92; P = 0.02), cefazolin (6% vs. 19%; aOR = 0.26, 95% CI 0.10-0.58; P < 0.001), ceftriaxone (2% vs. 6%; aOR = 0.25, 95% CI 0.04-0.93; P = 0.04) and trimethoprim/sulfamethoxazole (9% vs. 27%; aOR = 0.27, 95% CI 0.13-0.53; P < 0.001). The proportion of MDR E. coli declined from 31-36% during peak antimicrobial prescription to 11-14% in summer months; a 6.8% decline per interval decrease in antimicrobial prescription rates of 10/100 person-years (P = 0.01). There is significant seasonal variation in AMR rates of E. coli bloodstream isolates to four agents from frequently utilised antimicrobial classes in the community. Examination of seasonal variation in dominant serotypes of community-acquired E. coli bloodstream isolates in future will be valuable., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and 5.4% (95% CI 2.8, 8.0) and 7.1% (95% CI 4.2, 10.1), respectively, in patients with risk factors). Eighty-three of 105 (79%) NFGN were susceptible to ceftazidime overall and 20/29 (69%) in patients with prior beta-lactam use. Overall mean increase in susceptibilities was 15.2% (95% CI: 8.3, 22.2) and 17.1% (95% CI: 9.8, 24.5) for ciprofloxacin and gentamicin combinations, respectively; and 27.6% (95% CI: 10.3, 44.9) for either one with recent beta-lactam use. In this setting, empirical combination therapy had limited utility for Enterobacteriaceae bloodstream isolates but provided significant additional antimicrobial coverage to ceftazidime for NFGN, particularly in patients with prior beta-lactam use.