Prescribing Practices of Recommended Treatment for Trichomonas vaginalis and Chlamydia trachomatis after 2021 STI Treatment Guideline Update.

ABSTRACT: We evaluated the proportion of patients with trichomoniasis and chlamydial infections who received recommended versus non-recommended antibiotic therapy after the updated 2021 Sexually Transmitted Infections Guideline. Of 712 patients, 473 (66%) received recommended therapy. Receipt of emergency department care was independently associated with recommended therapy (adjOR, 2.1; 95% CI 1.5-2.9).

Leveraging stewardship to promote ceftriaxone use in severe infections with low- and no-risk AmpC Enterobacterales.

AmpC ß-lactamases are associated with development of ceftriaxone resistance despite initial in vitro susceptibility, but the risk of AmpC derepression is not equal among Enterobacterales. The purpose of this study was to evaluate the impact of an AmpC stewardship intervention on the definitive treatment of low- and no-risk Enterobacterales. This was an IRB-approved, single pre-test, post-test quasi-experiment at a 5-hospital system. An AmpC stewardship intervention was implemented in July 2022 and included prescriber education, the removal of microbiology comments indicating potential for ceftriaxone resistance on therapy, and the modification of a blood PCR comment for Serratia marcescens to recommend ceftriaxone. Adults ≥18 years pre-intervention (July 2021 to December 2021) and post-intervention (July 2022 to December 2022) who received ≥72 hours of inpatient definitive therapy and had non-urine cultures growing low- and no-risk organisms (S. marcescens, Providencia spp., Citrobacter koseri, Citrobacter amalonaticus, or Morganella morganii) were included. The primary endpoint was definitive treatment with ceftriaxone. A total of 224 patients were included; 115 (51%) in pre-intervention and 109 (49%) in post-intervention. Definitive ceftriaxone therapy was prescribed more frequently after intervention [6 (5%) vs 72 (66%), P < 0.001]. After adjustment for critical illness, patients in the post-group were more likely to receive definitive ceftriaxone (adjOR, 34.7; 95% CI, 13.9-86.6). The proportion of patients requiring retreatment was 18 (15%) and 11 (10%) for pre- and post-intervention patients (P = 0.22), and ceftriaxone resistance within 30 days occurred in 5 (4%) and 2 (2%) patients in the pre- and post-group (P = 0.45). An antimicrobial stewardship intervention was associated with increased ceftriaxone prescribing and similar patient outcomes for low- and no-risk AmpC Enterobacterales.

Impact of a Standardized, Pharmacist-Initiated "Test-Claim" Workflow for Anticipating Barriers to Accessing Discharge Antimicrobials.

Background: Inability to access and afford discharge oral antimicrobials may delay discharges or result in therapeutic failure. "Test-claims" have the potential to identify such barriers. Objective: This study evaluated discharge antimicrobial access and patient outcomes after implementation of a standardized, inpatient pharmacist-initiated antimicrobial discharge medication cost inquiry (aDMCI) process. Methods: This was an Institutional Review Board (IRB)-approved, pilot retrospective cohort study that included adults admitted for ≥72 hours from November 1, 2018, to February 28, 2019, and discharged on oral antimicrobials. Patients with a cost inquiry (aDMCI group) were compared with those without (standard-of-care, SOC, group). Primary endpoint was discharge delay. Secondary endpoints included percentage of patients discharged on suboptimal antimicrobials and medication errors from aDMCI. Results: 84 patients were included: 43 in SOC and 41 in aDMCI. Seventy-five antimicrobial cost inquiries were evaluated among 41 patients. There were no discharge delays or medication errors associated with the standardized "test-claim" (aDMCI) workflow. Patients in the SOC group had a greater Charlson Comorbidity Index (4 [2-6] vs 2 [1-4], P =0.004), were more likely to be immunosuppressed (24, 56% vs 12, 29%; P =0.014), and had longer hospitalization (8 [5-15] vs 6 [5-9] days, P =0.026). Primary access barriers were prior-authorization (8, 11%) and associated with linezolid and moxifloxacin cost inquiries. Most aDMCIs results were available in <24 hours (66, 88%). Conclusions: The aDMCI process is safe and offers an actionable transition of care tool that can identify barriers to accessing discharge medications while insulating patients from surprise out-of-pocket cost.

Cancer is chronic but antimicrobial stewardship is iconic: A retrospective cohort of optimal antibiotic use in ambulatory oncology clinics.

Objective: To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use. Methods: Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin-skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression. Results: In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19-4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P = .057). Conclusions: Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.

Implementation of indication-based antibiotic order sentences improves antibiotic use in emergency departments.

INTRODUCTION: Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED. METHODS: This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing. RESULTS: A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7-7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers. CONCLUSIONS: AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.

Aminopenicillins vs non-aminopenicillins for treatment of enterococcal lower urinary tract infections.

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections.

We compared optimal antibiotic prescribing before and after implementing an interpretive ß-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87).

Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection With a Focus on Immunocompromised Patients.

Objectives: Approximately 25% of patients with Clostridioides difficile infection (CDI) will experience recurrence, which is greater in immunocompromised patients. We report experience with an institutional guideline targeting high-risk immunocompromised patients. Methods: This was a retrospective cohort of consecutive patients with CDI who met institutional criteria for bezlotoxumab due to high risk for recurrent CDI between June 1, 2017, and November 30, 2018. The primary endpoint of recurrent CDI within 12 weeks was compared between patients who received the standard of care (SoC) plus or minus bezlotoxumab. Results: Twenty-three patients received bezlotoxumab infusion plus SoC and were compared to 30 SoC patients. 84% of patients were immunocompromised and 54.7% were transplant recipients. The primary endpoint occurred in 13% of bezlotoxumab patients compared to 23.3% of SoC patients. No serious adverse effects were identified. Conclusion: Bezlotoxumab was associated with a meaningful reduction in recurrent CDI in this cohort largely comprising immunocompromised and transplant patients. Larger studies are warranted to evaluate bezlotoxumab in this population.

Evaluating the Impact of Substance Use Disorder Resources on Outcomes of Persons Who Inject Drugs with Infections.

OBJECTIVE: The aim of the study is to evaluate the impact of inpatient substance use disorder (SUD) resources on outcomes of persons who inject stimulants and/or opioids (PWIDs) with infections. METHODS: This retrospective cohort evaluated PWIDs hospitalized from July 1, 2020, to May 31, 2021, and prescribed an antimicrobial course. The patients were compared based on inpatient implementation of SUD resources, including consultation of addiction medicine/behavioral health, implementation of an opioid withdrawal treatment protocol, or continuation/initiation of medications for opioid use disorder. The primary outcome was a composite of antibiotic completion, no unplanned discharge, and no 30-day readmission. Notable secondary outcomes included length of stay and presence of stigmatizing language in the electronic medical record. RESULTS: A total of 119 patients were analyzed-74 (62.2%) received SUD resources. The primary outcome was met by 43 patients with SUD resources implemented (58.1%) and 19 patients without resources (42.2%, P = 0.093). After adjustment for infection type, implementation of SUD resources (adjusted odds ratio, 2.593; 95% confidence interval, 1.162-5.789) was independently associated with primary outcome success. The patients who received SUD resources had a median length of stay of 7 days (4-13.3) compared with 4 days (2-6.5) in those without resources ( P < 0.001). Stigmatizing language was present in 98% of patient electronic medical records. CONCLUSIONS: Patient care provided to PWIDs with infections is optimized when SUD resources are implemented. This study further supports the necessity of improving SUD management when PWIDs are admitted to healthcare facilities.

Bridging the gap: An approach to reporting antimicrobial stewardship metrics specific to solid organ transplant recipients.

BACKGROUND: This study seeks to describe inpatient antimicrobial use (AU) utilizing the National Healthcare Safety Network-AU (NHSN-AU) framework among solid organ transplant recipients (SOTr) within 12 months after transplant. METHODS: This cross-sectional study included SOTr ≥ 18 years of age who underwent transplantation from January 2015 to December 2016 at a Midwestern US transplant center. Inpatient AU was followed for 12 months post-transplant. Hospital days present up to 12 months post-transplant, AU variables, and Clostridioides difficile infection (CDI) occurrences were analyzed. RESULTS: The cohort of 530 SOTr included 225 kidney (42.5%), 171 liver (32.3%), 45 lung (8.5%), 40 heart (7.5%), 39 multivisceral (7.4%), seven small bowel (1.3%), and three pancreas (0.6%) transplants. Total days of therapy (DOT) were 22 782 among the cohort, with a median of 5 days [interquartile range [IQR], 1-12]. Lung and liver transplants had the most total DOT (6571 vs. 5569 days), while lungs and small bowels had the highest median DOT (13 [IQR, 2-56] vs. 12 [IQR, 2-31]). The facility-wide DOT/1000 days were lowest in pancreas and highest in lung transplants (5.3 vs. 428.1). Small bowel transplants received the most resistant-Gram-positive infection and hospital-onset infection agents for facility-wide DOT/1000 days present. Pancreas and kidney transplants accounted for the most high-risk CDI agents. CDI occurred in 34 patients, with kidney and liver transplants experiencing 13 each. CONCLUSION: This study represents one of the first reports of AU in SOTr utilizing the NHSN-AU framework. More studies are needed for further peer-to-peer comparison of AU in this complex patient population.

The long-term sustainability of a respiratory culture nudge.

Resource-intensive interventions and education are susceptible to a lack of long-term sustainability and regression to the mean. The respiratory culture nudge changed reporting to "Commensal Respiratory Flora only: No S. aureus/MRSA or P. aeruginosa." This study demonstrated sustained reduction in broad-spectrum antibiotic duration and long-term sustainability 3 years after implementation.

Pharmacist-Driven Transitions of Care Practice Model for Prescribing Oral Antimicrobials at Hospital Discharge.

Importance: Although prescribers face numerous patient-centered challenges during transitions of care (TOC) at hospital discharge, prolonged duration of antimicrobial therapy for common infections remains problematic, and resources are needed for antimicrobial stewardship throughout this period. Objective: To evaluate a pharmacist-driven intervention designed to improve selection and duration of oral antimicrobial therapy prescribed at hospital discharge for common infections. Design, Setting, and Participants: This quality improvement study used a nonrandomized stepped-wedge design with 3 study phases from September 1, 2018, to August 31, 2019. Seventeen distinct medicine, surgery, and specialty units from a health system in Southeast Michigan participated, including 1 academic tertiary hospital and 4 community hospitals. Hospitalized adults who had urinary, respiratory, skin and/or soft tissue, and intra-abdominal infections and were prescribed antimicrobials at discharge were included in the analysis. Data were analyzed from February 18, 2020, to February 28, 2022. Interventions: Clinical pharmacists engaged in a new standard of care for antimicrobial stewardship practices during TOC by identifying patients to be discharged with a prescription for oral antimicrobials and collaborating with primary teams to prescribe optimal therapy. Academic and community hospitals used both antimicrobial stewardship and clinical pharmacists in a multidisciplinary rounding model to discuss, document, and facilitate order entry of the antimicrobial prescription at discharge. Main Outcomes and Measures: The primary end point was frequency of optimized antimicrobial prescription at discharge. Health system guidelines developed from national guidelines and best practices for short-course therapies were used to evaluate optimal therapy. Results: A total of 800 patients prescribed oral antimicrobials at hospital discharge were included in the analysis (441 women [55.1%]; mean [SD] age, 66.8 [17.3] years): 400 in the preintervention period and 400 in the postintervention period. The most common diagnoses were pneumonia (264 [33.0%]), upper respiratory tract infection and/or acute exacerbation of chronic obstructive pulmonary disease (214 [26.8%]), and urinary tract infection (203 [25.4%]). Patients in the postintervention group were more likely to have an optimal antimicrobial prescription (time-adjusted generalized estimating equation odds ratio, 5.63 [95% CI, 3.69-8.60]). The absolute increase in optimal prescribing in the postintervention group was consistent in both academic (37.4% [95% CI, 27.5%-46.7%]) and community (43.2% [95% CI, 32.4%-52.8%]) TOC models. There were no differences in clinical resolution or mortality. Fewer severe antimicrobial-related adverse effects (time-adjusted generalized estimating equation odds ratio, 0.40 [95% CI, 0.18-0.88]) were identified in the postintervention (13 [3.2%]) compared with the preintervention (36 [9.0%]) groups. Conclusions and Relevance: The findings of this quality improvement study suggest that targeted antimicrobial stewardship interventions during TOC were associated with increased optimal, guideline-concordant antimicrobial prescriptions at discharge.

Influence of Body Weight Category on Outcomes in Candidemia Patients Treated With Anidulafungin.

BACKGROUND: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. OBJECTIVES: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. METHODS: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration-labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. RESULTS: One hundred seventy-three patients were included. Candida albicans and Candida glabrata were identified in 58 (33%) and 57 (33%) patients, respectively. Mortality was comparable according to BMI category: 4 (36.4%) underweight, 8 (25.8%) normal weight, 16 (32.0%) overweight, 20 (33.9%) obese, and 7 (31.8%) morbidly obese, P = .976. Variables associated with mortality included: severe sepsis (adjusted odds ratio [OR] = 5.1, 95% CI: 1.7-14.8) and liver disease (adjusted OR = 3.2, 95% CI: 1.1-9.4). Variables that were protective of mortality included: line removal (adjusted OR = 0.05, 95% CI: 0.02-0.2) and receipt of anidulafungin for at least 5 days (adjusted OR = 0.35, 95% CI: 0.15-0.8). CONCLUSION: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients.

Evaluation of the selection of cerebrospinal fluid testing in suspected meningitis and encephalitis.

Diagnostic stewardship interventions can decrease unnecessary antimicrobial therapy and microbiology laboratory resources and costs. This retrospective cross-sectional study evaluated factors associated with inappropriate initial cerebrospinal fluid (CSF) testing in patients with suspected community-acquired meningitis or encephalitis. In 250 patients, 202 (80.8%) and 48 (19.2%) were suspected meningitis and encephalitis, respectively. 207 (82.8%) patients had inappropriate and 43 (17.2%) appropriate testing. Any inappropriate CSF test was greatest in the immunocompromised (IC) group (n = 54, 91.5%), followed by non-IC (n = 109, 80.1%) and HIV (n = 44, 80%). Ordering performed on the general ward was associated with inappropriate CSF test orders (adjOR 2.81, 95% CI [1.08-7.34]). Laboratory fee costs associated with excessive testing was close to $300,000 per year. A stepwise algorithm defining empiric and add on tests according to CSF parameters and patient characteristics could improve CSF test ordering in patients with suspected meningitis or encephalitis.

Outcomes of clinical decision support for outpatient management of Clostridioides difficile infection.

OBJECTIVE: To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment. DESIGN: Quasi-experimental study in >50 ambulatory clinics. SETTING: Primary, specialty, and urgent-care clinics. PATIENTS: Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020. INTERVENTIONS: An outpatient best practice advisory (BPA) was implemented to notify prescribers that "vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection" when metronidazole was prescribed to a patient with CDI. RESULTS: In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14-56 days of the initial episode (27% vs 7%; P < .001). CONCLUSIONS: Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.

High-Dose Daptomycin Is Well Tolerated via 2-Minute IV Push Administration.

BACKGROUND: The purpose of this study was to evaluate the safety of administering high-dose daptomycin (HDD; > 6 mg/kg actual body weight) as a 2-minute intravenous (IV) push (IVP) compared to traditional 30-minute IV piggyback (IVPB) infusion. METHODS: Retrospective cohort study comparing patients receiving HDD as an IVP or IVPB infusion. The primary outcome was the proportion of patients with a documented infusion-related reaction (IRR) to daptomycin. RESULTS: Three hundred patients were included in the final analysis, 200 patients received IVP, and 100 patients received IVPB representing a total of 1697 administrations. Median (IQR) daptomycin dose was IVP 700 mg (550-900) and IVPB 700 mg (600-900), with mg/kg doses of 8.2 (7.9-10) and 8.3 (8-10), respectively. After adjudication, IRR occurred in 1% of subjects in each treatment group. CONCLUSIONS: This study provides data in more than 1100 administrations of HDD administered via IVP. Infusion-related reactions were documented in 1% of patients regardless of infusion method, suggesting comparable safety to traditional infusion methods. This practice may be useful during fluid shortage and in the outpatient setting.

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases.

MOTIVATION: COVID-19 has several distinct clinical phases: a viral replication phase, an inflammatory phase and in some patients, a hyper-inflammatory phase. High mortality is associated with patients developing cytokine storm syndrome. Treatment of hyper-inflammation in these patients using existing approved therapies with proven safety profiles could address the immediate need to reduce mortality. RESULTS: We analyzed the changes in the gene expression, pathways and putative mechanisms induced by SARS-CoV2 in NHBE, and A549 cells, as well as COVID-19 lung versus their respective controls. We used these changes to identify FDA approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. We identified methylprednisolone (MP) as a potential leading therapy. The results were then confirmed in five independent validation datasets including Vero E6 cells, lung and intestinal organoids, as well as additional patient lung sample versus their respective controls. Finally, the efficacy of MP was validated in an independent clinical study. Thirty-day all-cause mortality occurred at a significantly lower rate in the MP-treated group compared to control group (29.6% versus 16.6%, P = 0.027). Clinical results confirmed the in silico prediction that MP could improve outcomes in severe cases of COVID-19. A low number needed to treat (NNT = 5) suggests MP may be more efficacious than dexamethasone or hydrocortisone. AVAILABILITY AND IMPLEMENTATION: iPathwayGuide is available at https://advaitabio.com/ipathwayguide/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sex differences in the time course and mechanisms of vascular and cardiac aging in mice: role of the smooth muscle cell mineralocorticoid receptor.

Aging is associated with heart and vascular dysfunction that contributes to cardiovascular disease (CVD) risk. Clinical data support a sexual dimorphism in the time course of aging-associated CVD. However, the mechanisms driving sex differences in cardiovascular aging and whether they can be modeled in mice have not been explored. Mineralocorticoid receptors (MRs) regulate blood pressure, and we previously demonstrated in male mice that MR expression increases in aging mouse vessels and smooth muscle cell-specific MR deletion (SMC-MR-KO) protects from cardiovascular aging. This study characterizes sex differences in murine cardiovascular aging and the associated sex-specific role of SMC-MR. Aortic stiffness, measured by pulse wave velocity, increased from 3 to 12 mo of age in males but not until 18 mo in females. The timing of the rise in aortic stiffening correlated with the timing of increased aortic MR expression, and aortic stiffness did not increase with age in SMC-MR-KO mice of both sexes. Vascular fibrosis increased at 12 mo in males and later at 18 mo in females; however, fibrosis was attenuated by SMC-MR-KO in males only. In resistance vessels, angiotensin type 1 receptor (AT1R)-mediated vasoconstriction also increased at 12 mo in males and 18 mo in females. ANG II-induced vasoconstriction was decreased in SMC-MR-KO specifically in males in association with decreased AT1R expression. Cardiac systolic function declined in males and females by 18 mo of age, which was prevented by SMC-MR-KO specifically in females. Cardiac perivascular fibrosis increased with age in both sexes accompanied by sex-specific changes in the expression levels of MR-regulated profibrotic genes.NEW & NOTEWORTHY These data demonstrate that the delayed and steeper decline in cardiovascular function observed in aging females can be modeled in aging mice. Moreover, the mechanisms driving vascular and cardiac aging phenotypes are distinct between males and females. Mineralocorticoid receptors in smooth muscle cells play a significant role in cardiovascular aging in both sexes; however, they do so by distinct mechanisms. Overall, these findings suggest that sex-specific therapies may be necessary to retard the aging process and improve cardiovascular disease outcomes in the aging population.

Impact of unit-specific metrics and prescribing tools on a family medicine ward.

OBJECTIVE: Prescribing metrics, cost, and surrogate markers are often used to describe the value of antimicrobial stewardship (AMS) programs. However, process measures are only indirectly related to clinical outcomes and may not represent the total effect of an intervention. We determined the global impact of a multifaceted AMS initiative for hospitalized adults with common infections. DESIGN: Single center, quasi-experimental study. METHODS: Hospitalized adults with urinary, skin, and respiratory tract infections discharged from family medicine and internal medicine wards before (January 2017-June 2017) and after (January 2018-June 2018) an AMS initiative on a family medicine ward were included. A series of AMS-focused initiatives comprised the development and dissemination of: handheld prescribing tools, AMS positive feedback cases, and academic modules. We compared the effect on an ordinal end point consisting of clinical resolution, adverse drug events, and antimicrobial optimization between the preintervention and postintervention periods. RESULTS: In total, 256 subjects were included before and after an AMS intervention. Excessive durations of therapy were reduced from 40.3% to 22% (P < .001). Patients without an optimized antimicrobial course were more likely to experience clinical failure (OR, 2.35; 95% CI, 1.17-4.72). The likelihood of a better global outcome was greater in the family medicine intervention arm (62.0%, 95% CI, 59.6-67.1) than in the preintervention family medicine arm. CONCLUSION: Collaborative, targeted feedback with prescribing metrics, AMS cases, and education improved global outcomes for hospitalized adults on a family medicine ward.