Evaluation of the impact of nasal colonization with methicillin-resistant Staphylococcus aureus on left ventricular assist device infections.

In this retrospective cohort study, we evaluated the predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs for the development of MRSA infections in patients with left ventricular assist devices. In 106 patients, the MRSA nasal swab had a negative predictive value of 92.9% demonstrating a potential role in antibiotic de-escalation.

Perceptions of a virtual interview process for pharmacy residents during the COVID-19 pandemic: A multisite survey of residency candidates, preceptors, and residency program directors.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions. METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods. RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews. CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

Clinical utility of negative methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs in skin and skin structure infections.

BACKGROUND: Negative methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs have a high negative predictive value of approximately 99% in respiratory infections. There is, however, a lack of data evaluating its use beyond respiratory infections. METHODS: We conducted a retrospective analysis to determine the clinical utility of MRSA swabs for identifying MRSA-associated skin and skin structure infections (SSSIs) and the potential effects on antimicrobial stewardship efforts. Baseline characteristics, culture data, and antibiotic data were collected to determine the difference in duration of vancomycin therapy. Positive predictive value, negative predictive value, sensitivity, and specificity were secondary outcomes. RESULTS: A total of 473 patients were included, of which 156 patients had a positive MRSA nasal swab and 317 patients had a negative swab. The median duration of vancomycin was 4 days in the positive group and 3 days in the negative group (P = .01). The positive predictive value and negative predictive value were 22.4% and 97.5%. The sensitivity and specificity were 81.4% and 71.9%. CONCLUSION: Patients with a negative MRSA nasal swab received approximately 1 day less of vancomycin, which represented a decrease in drug administered. The negative predictive value for SSSIs is promising, showing potential for the role of MRSA nasal swabs in de-escalating therapy.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2020.

The number of articles related to antimicrobial stewardship published each year has increased significantly over the last decade. Keeping up with the literature, particularly the most innovative, well-designed, or applicable to one's own practice area, can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network reviewed antimicrobial stewardship-related, peer-reviewed literature from 2020 that detailed actionable interventions. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for teaching and training, and to identify novel or optimized stewardship opportunities within one's institution.

Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature.

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on "Implementing an Antibiotic Stewardship Program" were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Perceptions of the two-phase pharmacy residency match process.

PURPOSE: To evaluate residency applicant (RA) and residency program director (RPD) perceptions of Phase II of the Match process since its inception in 2016. METHODS: An online survey was issued to all Match-registered RAs and RPDs for the 2016, 2017, and 2018 Match periods. Study participant demographics, participant designation (RA or RPD), the year(s) and Phase(s) of the Match participated in were measured using categorical ranges, and overall perceptions of the Match process since Phase II of the Match was implemented were captured with 5-point Likert scales. RESULTS: A total of 2,599 individuals (RA and RPD) completed the survey for an overall survey response rate of 12.6%. The majority of RAs were female (73.2%), under the age of 30 (87.4%), Caucasian (67.4%), and recently graduated (90.9% graduated between 2016 and 2018). Most RAs participated in the 2018 Match period (61%), and overall 82% successfully matched to a residency position. RA perceptions relating to process cost-effectiveness and perceived fairness to all applicants differed significantly from RPD perceptions (2.23 versus 3.71 and 2.80 versus 3.67, respectively; p < 0.001 for each). There were no differences between RA and RPD perceptions related to the submission/review process. CONCLUSION: The Phase II of the Match process has demonstrated improved organization and satisfaction from the RPD perspective compared to the previous process. RAs have identified several areas for improvement in the process. It is imperative that efforts are made to continue expanding program and position offerings as much as possible.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2018.

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2018. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training as well as to identify potential intervention opportunities within one's institution.

Survey of residency program directors' perceptions of nontraditional pharmacy residency applicants.

PURPOSE: The attitudes and expectations of residency program directors (RPDs) regarding nontraditional residency applicants (NTAs) were evaluated. METHODS: This was a cross-sectional, survey-based study targeting RPDs of American Society of Health-System Pharmacists-accredited residency programs. A 14-question survey requesting information related to demographics, perceptions of NTAs compared with traditional applicants, advantages and disadvantages of NTAs, and advice for NTAs was administered electronically to RPDs. The primary outcome of this study was to determine RPDs' perceptions of NTAs as suitable residency candidates. The secondary outcome evaluated the rate of NTA acceptance into residency programs and a qualitative assessment of RPDs' advice for NTAs. RESULTS: Of the 1,414 RPDs contacted to participate, 328 (23%) completed the survey. RPDs were primarily affiliated with postgraduate year 1 pharmacy practice (52%) or postgraduate year 2 specialty residencies (30%), and 35% reported having an NTA in their program. Most respondents (87%) reported that NTAs are given equal consideration relative to traditional residency applicants. RPDs rated work experience as the most important quality of an NTA, followed closely by the ability to work with others and teachability. Most (277 [85%]) RPDs agreed that NTAs should possess experiences beyond work experience, such as research, leadership, and community service. The biggest concern regarding NTAs was significant time since graduation prior to application. CONCLUSION: The majority of RPDs did not perceive NTAs differently from traditional applicants in the selection process of prospective candidates.

Syndrome-specific versus prospective audit and feedback interventions for reducing use of broad-spectrum antimicrobial agents.

BACKGROUND: Antimicrobial use (AU) of antipseudomonal ß-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.

Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections.

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 ß-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.

Neutral sphingomyelinase-2 mediates growth arrest by retinoic acid through modulation of ribosomal S6 kinase.

All-trans-retinoic acid (ATRA) induces growth arrest of many cell types. Previous studies have reported that ATRA can modulate cellular sphingolipids, but the role of sphingolipids in the ATRA response is not clear. Using MCF-7 cells as a model system, we show that ATRA stimulates an increase in ceramide levels followed by G(0)/G(1) growth arrest. Notably, induction of nSMase2 was the primary effect of ATRA on the sphingolipid network and was both time- and dose-dependent. Importantly, pretreatment with nSMase2 siRNA significantly inhibited ATRA effects on ceramide levels and growth arrest. In contrast, nSMase2 overexpression was sufficient to increase ceramide levels and induce G(0)/G(1) growth arrest of asynchronous MCF-7 cells. Surprisingly, neither ATRA stimulation nor nSMase2 overexpression had significant effects on classical cell cycle regulators such as p21/WAF1 or retinoblastoma. In contrast, ATRA suppressed phosphorylation of ribosomal S6 kinase (S6K) and its downstream targets S6 and eIF4B. Importantly, these effects were significantly inhibited by nSMase2 siRNA. Reciprocally, nSMase2 overexpression was sufficient to suppress S6K phosphorylation and signaling. Notably, neither ATRA effects nor nSMase2 effects on S6K phosphorylation required the ceramide-activated protein phosphatase PP2A, previously identified as important for S6K regulation. Finally, nSMase2 overexpression was sufficient to decrease translation as measured by methionine incorporation and analysis of polyribosome profiles. Taken together, these results implicate nSMase2 as a major component of ATRA-induced growth arrest of MCF-7 cells and identify S6K as a novel downstream target of nSMase2.