Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales.

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term "non-carbapenemase (NCP)", particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.

Evaluation of pharmacists' role in preoperative medication review in a Veterans Affairs Health Care System.

PURPOSE: Use of high-risk medications preoperatively may increase the incidence of postoperative complications. Available literature evaluating pharmacists' role in preoperative medication review is limited, and guidance is not currently available on which patients should have a medication review performed by a pharmacist before surgery. A preoperative rehabilitation pilot project in which clinical pharmacists reviewed medication profiles before scheduled surgeries was developed. This review aimed to evaluate pharmacists' role in reviewing medication profiles preoperatively and to identify specific patient factors that suggest a medication review is warranted. METHODS: This retrospective review utilized the electronic medical records of nonfrail adults undergoing preplanned surgeries enrolled in the pilot project from August 2021 to April 2022. Endpoints were determined using descriptive statistics and regression models. A multivariate analysis was performed evaluating high-risk medications and VIONE (Vital, Important, Optional, Not indicated, and Every medication has an indication) polypharmacy risk score. RESULTS: Forty patients were included, with at least one recommendation made in 83% of chart reviews. Many patients (95%) were taking at least one high-risk medication. Of the high-risk medication classes evaluated independently, only antiplatelets were predictive of pharmacy intervention (P = 0.01). Only high-risk medications were independently predictive of pharmacist intervention (P < 0.01) when multivariate analysis was performed. CONCLUSION: Pharmacists made a recommendation in the majority of medication reviews and were most likely to make a recommendation in patients taking high-risk medications. A larger sample size may provide more insight regarding patient-specific factors warranting a preoperative medication review.

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study.

BACKGROUND: Durvalumab is approved for the treatment of adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This real-world study describes patient characteristics and durvalumab treatment patterns (number of doses and therapy duration; treatment initiation delays, interruptions, discontinuations, and associated reasons) among VHA-treated patients. METHODS: This was a retrospective cohort study of adults with unresectable stage III NSCLC receiving durvalumab at the VHA between 1 January 2017 and 30 June 2020. Patient characteristics and treatment patterns were presented descriptively. RESULTS: A total of 935 patients were included (median age: 69 years; 95% males; 21% Blacks; 46% current smokers; 16% ECOG performance scores ≥ 2; 50% squamous histology). Durvalumab initiation was delayed in 39% of patients (n = 367). Among the 200 patients with recorded reasons, delays were mainly due to physician preference (20%) and CRT toxicity (11%). Overall, patients received a median (interquartile range) of 16 (7-24) doses of durvalumab over 9.0 (2.9-11.8) months. Treatment interruptions were experienced by 19% of patients (n = 180), with toxicity (7.8%) and social reasons (2.6%) being the most cited reasons. Early discontinuation occurred in 59% of patients (n = 551), largely due to disease progression (24.2%) and toxicity (18.2%). CONCLUSIONS: These real-world analyses corroborate PACIFIC study results in terms of the main reasons for treatment discontinuation in a VHA population with worse prognostic factors, including older age, predominantly male sex, and poorer performance score. One of the main reasons for durvalumab initiation delays, treatment interruptions, or discontinuations was due to toxicities. Patients could benefit from improved strategies to prevent, identify, and manage CRT and durvalumab toxicities timely and effectively.

A Survey of Vaping Use, Perceptions, and Access in Adolescents from South-Central Texas Schools.

Despite efforts to dissuade major manufacturers and retailers from marketing and selling vape products to adolescents, the practice of vaping continues to increase in this population. Few studies have assessed adolescent perceptions of vaping, access to vaping, and use of vaping, and most rely, at least in part, on inferential conclusions drawn from data on smoking traditional combustible cigarettes. A novel electronic survey was created to assess the use of vapes, perceptions of vaping, and access to vaping among a convenience sample of adolescents (ages 12-20 years) in eleven schools in South-Central Texas from May to August 2021. The students' perceived threat of negative health outcomes due to vaping was calculated based on questions soliciting perceptions of severity (perceived danger) and susceptibility (perceived likelihood of illness). Trends were identified using descriptive and bivariate statistical tests. A total of 267 respondents were included; 26% had tried vaping. A majority (63%) did not believe vaping and smoking were synonymous. Most (70%) thought it was easy to obtain supplies and (76%) vape before and after (88%) or even during (64%) school. Respondents who vaped had a 34% lower perceived threat when compared to respondents who did not vape. In this sample of adolescents from South-Central Texas, one in four reported that they had tried vaping. Easy access to vapes and misperceptions regarding the safety of vaping might create a false sense of security with respect to vaping as an alternative to smoking, particularly among those who reported vaping, and is likely contributing to the increased use of vapes.

Outcomes in Patients With Curative Malignancies Receiving Filgrastim as Primary Prophylaxis.

Background: Granulocyte colony-stimulating factor prophylaxis has been shown to reduce the risk and duration of chemotherapy-induced neutropenia and febrile neutropenia and is recommended for at-risk patients receiving chemotherapy. Within the South Texas Veterans Health Care System, daily filgrastim injections remain the preferred formulation of granulocyte colony-stimulating factor for primary prophylaxis of febrile neutropenia. Methods: This retrospective, single-center cohort study included 59 patients who received daily filgrastim as primary prophylaxis with a curative cancer diagnosis and a chemotherapy regimen at the South Texas Veterans Health Care System from September 1, 2015 to September 24, 2020. Patients had either a high risk for febrile neutropenia or a chemotherapy regimen with an intermediate risk for febrile neutropenia and additional risk factors. The primary outcome was the incidence of neutropenia/febrile neutropenia leading to treatment delays. Secondary outcomes included chemotherapy dose decreases or discontinuations, hospitalizations, days of hospitalization, infections, extended duration of filgrastim, and transitions to pegfilgrastim due to neutropenia/febrile neutropenia. Results: Patients received a median (IQR) of 7 (5-10) doses of filgrastim for primary prophylaxis. Overall, 10 patients (17%) experienced treatment delays due to neutropenia/febrile neutropenia. Fifteen patients (25%) were hospitalized with a median (IQR) length of stay of 5 (4-7) days, 9 patients (15%) had documented infections, and 2 patients (3%) required a chemotherapy dose reduction. Additionally, 9 patients (15%) required an additional median (IQR) of 2 (2-5) doses of filgrastim, and 9 (15%) patients were transitioned to pegfilgrastim. Conclusions: These results suggest that additional measures such as tracking postnadir absolute neutrophil counts should be performed to ensure patients receive an appropriate number of filgrastim doses to prevent complications associated with neutropenia/febrile neutropenia.

Inclusion of postdoctoral trainees in a translational science training TL1 program was associated with greater diversification of research across the translational science continuum: a bibliometric analysis of TL1 trainee publications.

The NIH National Center for Advancing Translational Science (NCATS) was established to support translational research that spans the entire TS Continuum, with the goal of bridging the gap between preclinical biomedical research and real-world applications to advance treatments to patients more quickly. In 2018, the Translational Science Training (TST) TL1 Program at the University of Texas Health Science Center at San Antonio implemented new strategies to better include and encourage research more broadly across the TS Continuum, including the addition of postdoctoral scientists and a clinically trained Program Co-Director, expansion of team science and community engagement programming, and targeted trainee recruitment from schools of nursing, dentistry, and allied health, in addition to medicine. The objective of this bibliometric analysis was to determine if the program exhibited a more diverse mix of T-types after the adjustments made in 2018. The TST/TL1 Program experienced a shift in T-type, from mostly T0 (preclinical) to more T3/T4 (clinical implementation/public health) research, after new strategies were implemented. This supports the conclusion that strategic programmatic adjustments by an NCATS-funded predoctoral training program resulted in outcomes that better align with NCATS priorities to develop Trainees who contribute across the entire TS Continuum.

Antibiotic prescribing by age, sex, race, and ethnicity for patients admitted to the hospital with community-acquired bacterial pneumonia (CABP) in the All of Us database.

Purpose: To assess the proportion of inpatients who received guideline-concordant antibiotics for community-acquired bacterial pneumonia (CABP) in special populations of the All of Us database. Background: CABP contributes significantly to healthcare burden worldwide. The American Thoracic Society and Infectious Disease Society of America jointly published guidelines for the treatment of CABP. Guideline-concordant antibiotics for CABP are associated with better patient and cost outcomes. Methods: This was a retrospective cohort study of patients with pneumonia (n = 1608; SNOMED 233604007) from 10/1/2018 to 1/01/22 in the All of Us database. Cases were excluded for treatment setting other than inpatient, prior (within 90 days) pneumonia, receipt of intravenous antibiotics, respiratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, and/or other non-community-acquired types of pneumonia. Patients were grouped based on patient age, sex, race, and ethnicity. The proportion of patients on guideline-concordant therapy was compared within groups using chi-square statistics. Significant associations were assessed using multivariate logistic regression models. Results: A total of 1608 cases were included, and 45% of these patients received guideline-concordant antibiotics. Non-Hispanic White (NHW) patients vs. Black patients were associated with a 36% higher likelihood for receiving guideline-concordant antibiotics (adjusted OR, 1.36; 95% CI 1.02-1.81), whereas NHW vs. Hispanic patients were associated with a 34% lower likelihood for receiving guideline-concordant antibiotics (aOR 0.66; 0.48-0.91). Conclusion: Black patients with CABP in the All of Us database were less likely to receive guideline-concordant antibiotics, and Hispanic patients were more likely to receive guideline-concordant antibiotics, than NHW patients.

Incidence of invasive fungal infections in patients with chronic lymphocytic leukemia receiving ibrutinib within the veteran's healthcare administration.

PURPOSE: Ibrutinib is a tyrosine kinase inhibitor that is increasingly prescribed in chronic lymphocytic leukemia (CLL). Invasive fungal infections (IFIs) have been reported early after ibrutinib initiation. Timing of IFIs is within 6 months and commonly reported fungal infections include Cryptococcus, Aspergillus, and Pneumocystis. Currently, there are no recommendations for routine prophylaxis against IFIs in patients receiving ibrutinib for CLL. OBJECTIVE: The objective of this study was to evaluate the incidence of IFIs in patients receiving ibrutinib for CLL in first-line and relapsed/refractory (R/R) settings. METHODS: This was a retrospective, cohort study of patients diagnosed with CLL and initiated on ibrutinib in the Veterans Health Administration (VHA) from October 1, 2013 to March 31, 2018. Patients were included if diagnosed with a proven or probable IFI from the start date of ibrutinib to 30 days after the last dose of ibrutinib. RESULTS: Fourteen out of 1069 patients met inclusion criteria for IFI while on ibrutinib for CLL. All patients included were male with a median age of 78 years. Fifty percent of patients were initiated on ibrutinib within 3 months of last chemotherapy. IFIs occurred within 3 months (50%) and 6 months (71%) of ibrutinib initiation. Seventy-one percent of patients were continued on ibrutinib with concurrent IFI diagnosis. CONCLUSION: The reported IFI incidence of 1.3% is comparable to current estimates of 1.2%. Future studies should examine the relationship of ibrutinib and incidence of IFIs in first-line and R/R settings in addition to identifying clinical risk factors predisposing patients to IFIs.

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration.

BACKGROUND: Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population. MATERIALS AND METHODS: This was a retrospective analysis of White and Black adults with unresectable stage III NSCLC treated with durvalumab presenting to any VHA facility in the US from January 1, 2017, to June 30, 2020. Data captured included baseline characteristics and durvalumab treatment patterns, including treatment initiation delay (TID), interruption (TI), and discontinuation (TD); defined as CRT completion to durvalumab initiation greater than 42 days, greater than 28 days between durvalumab infusions, and more than 28 days from the last durvalumab dose with no new durvalumab restarts, respectively. The number of doses, duration of therapy, and adverse events were also collected. RESULTS: A total of 924 patients were included in this study (White = 726; Black = 198). Race was not a significant factor in a multivariate logistic regression model for TID (OR, 1.39; 95% CI, 0.81-2.37), TI (OR, 1.58; 95% CI, 0.90-2.76), or TD (OR, 0.84; 95% CI, 0.50-1.38). There were also no significant differences in median (interquartile range [IQR]) number of doses (White: 15 [7-24], Black: 18 [7-25]; P = .25) or median (IQR) duration of therapy (White: 8.7 months [2.9-11.8], Black: 9.8 months [3.6-12.0]; P = .08), although Black patients were less likely to experience an immune-related adverse event (28% vs. 36%, P = .03) and less likely to experience pneumonitis (7% vs. 14%, P < .01). CONCLUSION: Race was not found to be linked with TID, TI, or TD in this real-world study of patients with unresectable stage III NSCLC treated with durvalumab at the VHA.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. METHODS: Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). RESULTS: 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069. CONCLUSION: Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Health disparity in use of novel agents for first-line therapy in Black and White patients with chronic lymphocytic leukemia in the Department of Veterans Affairs.

BACKGROUND: Novel agents (NAs) (ibrutinib, idelalisib, and venetoclax) were first introduced in 2013 as therapeutic options to treat chronic lymphocytic leukemia (CLL). OBJECTIVES: To determine if the uptake of NAs for first-line treatment was similar in Black and White patients with CLL treated in the Department of Veterans Affairs (VA). METHODS: We conducted a retrospective cohort study including adults with CLL managed in the VA from October 1, 2013, to September 30, 2017. Descriptive statistics were used to summarize demographic data, and appropriate bivariable statistical tests were used to compare NA use, baseline characteristics, health outcomes, and complications. A multivariable logistic regression model was used to identify factors associated with uptake of NAs. The study included 565 patients; 86% were White and 14% were Black. Black patients were younger than White patients (median age [66 vs 69 years; P < 0.01]) but had similar median baseline Charlson comorbidity scores (4 vs 5). RESULTS: Overall, Black patients were less likely to receive NAs than White patients (14% vs 26%; P = 0.02). The gap narrowed over the study period: 4% vs 17% (2014), 13% vs 25% (2015), 17% vs 33% (2016), and 31% vs 33% (2017). Black race (P = 0.02) and fiscal year (P < 0.01) were the only variables significantly associated with NA use in the multivariable model. Health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. CONCLUSIONS: This is the first study to identify a potential health disparity with respect to use of NAs among Black and White patients with CLL treated in the VA. Fortunately, health outcomes and most complications were similar for Black and White patients despite the difference in prescribing patterns. DISCLOSURES: Funding for the study was provided by AstraZeneca as a research grant to the Foundation for Advancing Veterans' Health Research (FAVHR), a non-profit entity within the Audie L. Murphy Veterans Hospital, San Antonio, TX. Drs Nooruddin and Frei have received research grants (paid to FAVHR) from AstraZeneca in the last 3 years. Ms Ryan is an employee of AstraZeneca. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the National Institutes of Health, or the authors' affiliated institutions.

Comparison of bibliometrics for predoctoral Translational Science Training (TST) TL1 Program participants and nonparticipants, male and female participants, and participants from underrepresented and well-represented backgrounds.

Research education and training in Translational Science develops and sustains a workforce to efficiently advance studies designed to improve human health. We evaluated the effectiveness of a Translational Science Training (TST) TL1 Program. Participants had significantly better publications/year, citations/year, h-index, and m-quotient than nonparticipants. Female and male participants, and participants from underrepresented and well-represented backgrounds, performed similarly on all bibliometric assessments. Finally, TST/TL1 Program participants outperformed students from other PhD programs at our institution. This analysis suggests that the TST/TL1 Program has been effective for participants, including those who are female and from underrepresented backgrounds.

Electronic cigarette or vaping use among adolescents in the United States: A call for research and legislative action.

Vaping among adolescents is increasingly common and may result in poor health outcomes; however, little research has been conducted evaluating the risks of vaping among adolescents and the knowledge and perceptions that drive use. We must gain a better understanding of vaping outcomes and adolescents' perceptions while identifying potential ways to lessen or eradicate the health burdens associated with vaping. This knowledge could then inform robust educational and public health programs to prevent and mitigate vaping among youths. Health education incorporating a target populations' world view, spheres of influence, readiness, motivation, intention, and determination promotes informed decision making. There are few resources currently being allocated to the problem even though legislators and enforcement agencies are aware. We cannot simply rely on existing laws to serve as a sufficient deterrent to prevent underaged usage. Further efforts are needed in the areas of behavioral science, health education, and public policy to tackle this urgent public health concern.

Retrospective Cohort Evaluating the Comparative Effectiveness of Ceftaroline and Daptomycin as First-Line Therapies for Inpatient Treatment of Diabetic Foot Infection in the United States Veterans Health Care System.

BACKGROUND: Both ceftaroline and daptomycin are possible therapeutic options for diabetic foot infection (DFI) and both are active against methicillin-resistant Staphylococcus aureus (MRSA) infection; however, no previous studies have evaluated their effectiveness head-to-head. OBJECTIVE: This study compared hospital readmission and mortality proportions among patients receiving ceftaroline fosamil or daptomycin for DFI. PATIENTS AND METHODS: This was a retrospective cohort, comparative effectiveness study of adults (aged ≥ 18 years) admitted to United States Veterans Health Care System hospitals with a diagnosis code for DFI between 1 October 2010 and 30 September 2014 with an electronic order for ceftaroline or daptomycin as first-line therapy within 14 days of admission. Baseline characteristics were compared using Chi-square, Fisher's exact, and Wilcoxon rank-sum tests. Hospital readmission and patient mortality proportions were compared through multivariable logistic regression models with Hispanic ethnicity, prior hospitalization, dyslipidemia, and Charlson comorbidity score as covariates. RESULTS: In total, 223 patients were included (ceftaroline, n = 71; daptomycin n = 152). At baseline, ceftaroline patients were more likely to be Hispanic (18 vs. 6%, p < 0.01) and have been hospitalized in the past 90 days (34 vs. 19%, p = 0.02). Unadjusted 90-day hospital readmission proportions for ceftaroline versus daptomycin were 34 vs. 49%, and unadjusted 90-day mortality proportions were 1% vs. 8%. In multivariable models, ceftaroline patients were less likely to experience 90-day hospital readmission (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25-0.85) and 90-day mortality (OR 0.14, 95% CI 0.01-0.77). CONCLUSIONS: In this population, ceftaroline was associated with lower 90-day hospital readmission and 90-day mortality compared with daptomycin when used as first-line therapy for DFI.

Delirium Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Ertapenem, cefepime, imipenem, ofloxacin, ceftazidime, clarithromycin, cefaclor, levofloxacin, linezolid, moxifloxacin, azithromycin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, metronidazole, ciprofloxacin, and cefuroxime are known to be associated with delirium. Other antibiotics may also lead to delirium, but no study has systemically compared delirium associations for many available antibiotics. OBJECTIVE: The objective of this study was to evaluate the association between delirium and antibiotics using the FDA Adverse Event Reporting System (FAERS). METHODS: FAERS reports from January 1, 2004 to December 31, 2018 were included in the study. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (95% CI) for the association between antibiotics and delirium were calculated. An association was considered to be statistically significant when the lower limit of the 95% CI was greater than 1.0. RESULTS: A total of 10,015,622 reports (including 16,982 delirium reports) were considered, after inclusion criteria were applied. Statistically significant delirium RORs (95% CI) for antibiotics were: ertapenem 21.07 (16.38-27.10), cefepime 9.8 (6.37-15.09), imipenem 9.68 (6.75-13.89), ofloxacin 7.73 (4.00-14.92), ceftazidime 6.09 (2.73-13.62), clarithromycin 5.34 (4.37-6.53), cefaclor 5.32 (1.71-16.58), ampicillin-sulbactam 4.49 (2.13-9.45), levofloxacin 4.47 (3.88-5.16), linezolid 4.33 (3.28-5.72), moxifloxacin 3.51 (2.81-4.38), azithromycin 2.76 (2.09-3.64), piperacillin-tazobactam 2.41 (1.47-3.93), trimethoprim-sulfamethoxazole 2.36 (1.61-3.47), metronidazole 1.85 (1.31-2.60), ciprofloxacin 1.83 (1.44-2.33), and cefuroxime 1.81 (1.03-3.20). CONCLUSION: This study found statistically significant increased risk of reporting delirium with ertapenem, cefepime, imipenem, ofloxacin, ceftazidime, clarithromycin, cefaclor, ampicillin-sulbactam, levofloxacin, linezolid, moxifloxacin, azithromycin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, metronidazole, ciprofloxacin, and cefuroxime.

In vitro activity of non-antibiotic drugs against Staphylococcus aureus clinical strains.

OBJECTIVES: We hypothesised that one or more of the non-antibiotic candidates selected for this study would demonstrate antibiotic activity against Staphylococcus aureus. METHODS: We determined minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for non-antibiotic drugs (amlodipine, azelastine, ebselen and sertraline) against five clinical S. aureus isolates and one quality control strain using the Microplate Alamar Blue Assay (MABA). Our research group selected clinical isolates obtained from nasal and wound swab cultures of patients with skin and soft-tissue infections who were seen at primary care clinics in the South Texas Ambulatory Research Network (STARNet). RESULTS: Three of the non-antibiotic drugs had identical MICs for all isolates: amlodipine, 64 µg/mL; azelastine, 200 µg/mL; and sertraline, 20 µg/mL. MICs for ebselen were 0.25 µg/mL (SA-29213, A1019 and J1019), 0.5 µg/mL (A32 and B60) and 1 µg/mL (B72). MBCs for amlodipine, azelastine and sertraline were within one dilution of their MICs, indicating bactericidal activity for all test isolates. Ebselen MBCs were one to two dilutions higher in most isolates, also indicating bactericidal activity for all test isolates. CONCLUSION: In summary, all four non-antibiotics demonstrated in vitro activity to varying degrees against S. aureus clinical isolates. Ebselen was the most potent of the four non-antibiotics tested.

Clinical impact of implementation of rapid diagnostic testing of blood cultures with Staphylococcus aureus on patient outcomes.

Rapid diagnostic testing in microbiology labs shortens the time to identification of bacteria in blood cultures. Cepheid® GeneXpert® MRSA/SA PCR can be used to distinguish MRSA and MSSA from non-Staphylococcus aureus organisms in blood cultures. This study aims to determine if implementation of MRSA/SA PCR for blood culture pathogen identification, plus daily antimicrobial stewardship intervention, can reduce time to appropriate therapy, vancomycin duration, 30 day mortality, and 90 day recurrence in veterans. A total of 113 patients in the pre-implementation cohort and 73 patients in the post-implementation cohort were evaluated. Time to appropriate therapy was decreased from 49.8 (pre-implementation) to 20.6 (post-implementation) hours. There was a numerically shorter median duration of vancomycin therapy in the post-implementation group. There was no difference in 30 day mortality or 90 day recurrence between groups. Use of MRSA/SA PCR can improve antimicrobial use when combined with once-daily antimicrobial stewardship review.

Brief Overview of Approaches and Challenges in New Antibiotic Development: A Focus On Drug Repurposing.

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as "antibiotic adjuvants" to enhance the activity of certain antibiotics.