Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia.

BACKGROUND: The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection. OBJECTIVE: We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB. METHODS: This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation. RESULTS: Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively. CONCLUSIONS AND RELEVANCE: D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.

Does a Positive Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screen Predict the Risk for MRSA Skin and Soft Tissue Infection?

BACKGROUND: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited. OBJECTIVE: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs. METHODS: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel. RESULTS: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%. CONCLUSIONS: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Accuracy of 4 Free Online Dosing Calculators in Predicting the Vancomycin Area Under the Concentration-Time Curve Calculated Using a 2-Point Pharmacokinetic Approach.

BACKGROUND: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described. OBJECTIVE: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use. METHODS: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale. RESULTS: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use. CONCLUSION AND RELEVANCE: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection. METHODS: In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021-11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. RESULTS: Of 10 036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% vs 5.7%; adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], .19-.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% vs 1.0%; aOR, 0.11; 95% CI, .0-.79), and may reduce respiratory disease severity among those hospitalized. CONCLUSIONS: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Plasma and cerebrospinal fluid concentrations of cefiderocol during successful treatment of carbapenem-resistant Acinetobacter baumannii meningitis.

BACKGROUND: To date, no real-world data are available to describe cefiderocol use in carbapenem-resistant Acinetobacter baumannii (CRAB) meningitis. Furthermore, cefiderocol pharmacokinetic (PK) data to support CNS penetration in human subjects are limited. These gaps pose a significant concern for clinicians who are faced with treating such infections when considering cefiderocol use. OBJECTIVES: To describe cefiderocol CSF and plasma PK and pharmacodynamic (PD) data from two different dosing regimens [2 g IV q6h (regimen 1) and 2 g IV q8h (regimen 2)] during treatment of CRAB meningitis. PATIENTS AND METHODS: A 61-year-old woman with CRAB meningitis was treated with cefiderocol and intraventricular gentamicin. Steady-state plasma and CSF cefiderocol concentrations were evaluated on Day 19 (regimen 1) and Day 24 (regimen 2) during the cefiderocol treatment course. RESULTS: CSF AUC was 146.49 and 118.28 mg·h/L, as determined by the linear-log trapezoidal method for regimens 1 and 2, respectively. Penetration into CSF estimated as the AUCCSF/AUCfree plasma ratio was 68% and 60% for regimens 1 and 2, respectively. Estimated free plasma and CSF concentrations exceeded the MIC of the isolate for 100% of the dosing interval. Microbiological and clinical cure were achieved, and no cefiderocol-associated adverse effects were observed. CONCLUSIONS: Cefiderocol, when given as 2 g q8h and 2 g q6h, attained CSF concentrations that exceeded the organism-specific MIC and the CLSI susceptible breakpoint (≤4 mg/L) for 100% of the dosing interval.

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. METHODS: This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. RESULTS: COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52-5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01-3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20-3.82), obesity (OR 1.79, 95% CI 1.36-2.34), one comorbidity (OR 1.68, 95% CI 1.11-2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13-2.35), and male sex (OR 1.56, 95% CI 1.21-2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). CONCLUSIONS: Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

Hospital Discharge: An Opportune Time for Antimicrobial Stewardship.

BACKGROUND: Approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting, and limited data describe AS interventions at hospital discharge. Acknowledging the potential value of discharge AS, we used our existing resources to review discharge oral antimicrobial prescriptions. OBJECTIVE: The primary objective of this retrospective, single-center study was to evaluate the impact of an AS program on discharge oral antimicrobial prescriptions. METHODS: Discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious diseases (ID) pharmacist, and recorded into our data collection tool from September 1, 2020, to February 28, 2021, were evaluated retrospectively. The primary outcome was to identify the frequency a drug-related problem (DRP) was identified by an ID pharmacist. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted. RESULTS: Of the 803 discharge oral antimicrobial prescriptions reviewed, at least 1 DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. At least 1 intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). The most common types of interventions included recommendations for a different duration, a different dose or frequency, and antimicrobial discontinuation. When interventions to reduce treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5-10) days to 4 (0-5.5) days (P < 0.001). CONCLUSION AND RELEVANCE: An ID pharmacist's review of discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.

Lexical restructuring stimulates phonological awareness among emerging English-French bilingual children's literacy.

This longitudinal study investigated how lexical restructuring can stimulate emerging bilingual children's phonological awareness in their first (L1) and second (L2) languages. Sixty-two English (L1) - French (L2) bilingual children (Mage = 75.7 months, SD = 3.2) were taught new English and French word pairs differing minimally in phonological contrast. The results indicated that increasing lexical specificity in English mediated the relationship between English vocabulary and English phonological awareness both concurrently and longitudinally at the end of Grade 1. A longitudinal relationship was established among French vocabulary, French lexical specificity, and French phonological awareness at the end of Grade 1. Notably, cross-language transfer from English lexical specificity was a better predictor of development in French phonological awareness, especially for words that contained phonological contrasts that occurred in both languages. The results from this study highlight the phonological foundations of early literacy and extend the lexical restructuring hypothesis to emerging bilingual children.

Validation of Methicillin-Resistant Staphylococcus aureus (MRSA) Risk Factors in Predicting MRSA Community-Acquired Pneumonia at an Academic Medical Center.

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

Cefiderocol: a novel siderophore cephalosporin for multidrug-resistant Gram-negative bacterial infections.

Cefiderocol is a novel siderophore cephalosporin that forms a complex with extracellular free ferric iron, which leads to transportation across the outer cell membrane to exert its bactericidal activity through cell wall synthesis inhibition. This pharmacological property has rendered cefiderocol active against several clinically relevant MDR Gram-negative bacteria as evidenced by several in vitro and in vivo studies. Cefiderocol was first approved by the US FDA on 14 November 2019 for the treatment of complicated urinary tract infections. On 28 September 2020, cefiderocol was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The FDA-approved indications are based on clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In APEKS-cUTI, cefiderocol demonstrated non-inferiority to imipenem/cilastatin for the treatment of complicated urinary tract infection caused by MDR Gram-negative bacteria. In APEKS-NP, cefiderocol demonstrated non-inferiority to meropenem for treatment of nosocomial pneumonia. However, in CREDIBLE-CR, higher all-cause mortality was observed with cefiderocol compared with best available therapy for the treatment of severe infections caused by Gram-negative bacteria, primarily in the subset of patients with Acinetobacter spp. infections. Several case reports/series have demonstrated clinical success with cefiderocol for a variety of severe infections. The purpose of this article is to review available data on the mechanism of action, in vitro and in vivo data, pharmacokinetics, pharmacodynamics, susceptibility testing, efficacy and safety of cefiderocol to address its role in therapy.

Articulatory settings and L2 English coronal consonants.

Background/aims: We explore the potential contribution of Articulatory Settings (AS) theory to L2 speech production research, testing the hypothesis that L2 segmental speech learning should involve a gradual, overall shift in both place and constriction degree, simultaneously affecting all consonants of a series as opposed to a set of parallel but unrelated changes in learners' production of individual sounds. Methods: We conducted an electropalatography study of four francophone learners' production of French and English word-initial and -medial /t d s z n l/ via carrier-sentence reading tasks. Results: L1-L2 differences in tongue shape are more common than those in constriction location, first and foremost for sonorants, and, thus, our results are not completely consistent with AS theory's claims. Conclusions: AS theory provides a potentially rich framework for exploring the L2 speech learning of consonantal phenomena including low-level L1-L2 differences in place of articulation. We propose that the observed lack of systematic between-language articulatory differences could be attributed to a number of factors to be explored in future research, such as the targeting of voicing and manner differences before the adjustment of small place differences as well as individual patterns of entrenchment of L1 articulatory routines.

Cost comparison of AUC:MIC- versus trough-based vancomycin monitoring for MRSA bacteremia.

OBJECTIVES: It is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)-based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC-based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC- or trough-based monitoring. DESIGN: This was a single-center, retrospective cohort study. SETTING AND PARTICIPANTS: This study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC-based monitoring at our institution. OUTCOME MEASURES: The primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay. RESULTS: A total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07-$601.05) for the AUC:MIC-based group compared with $316.79 ($253.36-$520.96) for the trough-based group (P = 0.687). CONCLUSION: Vancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution.

The Culture of Carbapenem Overconsumption: Where Does It Begin? Results of a Single-Center Survey.

Purpose: The United States has seen an increased consumption of carbapenem antibiotics in recent years. The increased utilization of these agents has potential negative consequences, including the increasing incidence of carbapenem-resistant Enterobacteriaceae. Reasons for the rise in carbapenem use among providers in acute care hospitals are not well elucidated in literature. The objectives of this study were to identify factors that influence empiric carbapenem use among providers in a single academic medical center, and to assess therapeutic knowledge pertaining to carbapenem use. Methods: A cross-sectional, single-center, 9-item electronic research survey was developed independently and validated by an infectious diseases pharmacist and infectious diseases physician. The survey was distributed to email accounts of providers at a single academic medical center. Demographic data, factors affecting carbapenem prescription, and baseline therapeutic knowledge were assessed. Results: Ninety-five of 416 providers responded to the survey (response rate of 22.8%). Respondents were well distributed across all levels of training with primary roles in internal medicine and surgery. The most important factors influencing empiric carbapenem use were suspected pathogens at the site of infection, drug allergies, history of multidrug resistant organisms, severity of illness, type of infection, and local resistance rates. A recommendation from a pharmacist was selected as the most likely factor for deterring carbapenem use. Misconceptions pertaining to penicillin drug allergy and beta-lactam cross reactivity, knowledge of local resistance rates according to the institutional antibiogram, and comparative efficacy data for carbapenems were apparent across all levels of training. Conclusions: Provider misconceptions regarding several factors appear to contribute to unnecessary use of carbapenems. An opportunity exists for hospital pharmacists to improve the prescribing patterns of carbapenems by correcting provider misconceptions through education.

Clinical review of delafloxacin: a novel anionic fluoroquinolone.

Delafloxacin is a novel anionic fluoroquinolone (FQ) approved for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by a number of Gram-positive and Gram-negative organisms including MRSA and Pseudomonas aeruginosa. The unique chemical structure of delafloxacin renders it a weak acid and results in increased potency in acidic environments. In Phase III studies, delafloxacin had similar outcomes to comparator regimens for treatment of ABSSSIs, and was well tolerated overall. Similar to other FQs, delafloxacin is available in both intravenous and oral formulations, but differs in that delafloxacin exerts a minimal effect on cytochrome P450 enzymes and on the corrected QT interval. This novel FQ has the potential to be utilized across a wide variety of clinical settings; however, post-marketing surveillance and long-term safety and resistance data will be essential to identify optimal use scenarios.

Impact of a pharmacist-driven beta-lactam allergy interview on inpatient antimicrobial therapy: A pilot project.

OBJECTIVES: To determine the impact of a pharmacist-driven beta-lactam allergy interview on antimicrobial therapy. SETTING: Tertiary care academic medical center. PRACTICE SETTING: Clarification of beta-lactam allergy may expand treatment options for patients and potentially improve outcomes, reduce toxicity, and reduce costs. PRACTICE INNOVATION: At our institution, a pilot service using a pharmacy resident and infectious diseases clinical pharmacist was implemented to clarify beta-lactam allergy information and, where appropriate, recommend a change to the patient's antibiotic therapy. EVALUATION: Adult patients with a documented beta-lactam allergy who had received non-penicillin antibiotics and who had undergone a beta-lactam allergy interview were identified via pharmacy intervention data. A pharmacist interviewed these patients with the use of an internally developed allergy questionnaire. Recommendations for beta-lactam therapy were made to the patient's primary medical team based on the results of the allergy interview and factors including infection type and culture results. The primary objectives were to determine the percentage of patients successfully switched to beta-lactam therapy as a result of the drug allergy interview, to identify allergy discrepancies between the electronic medical record (EMR) and pharmacist's interview, and to quantify the acceptance rate of the pharmacist's antimicrobial recommendations after drug allergy clarification. RESULTS: Thirty-two patients were interviewed, and 24 were candidates for a beta-lactam recommendation. As a result of the interview, 21 patients (65.6%) were successfully switched from a non-penicillin antibiotic to a cephalosporin, carbapenem, or penicillin. A discrepancy between the EMR-reported allergy and history obtained on interview was identified in 11 patients (34.4%). Medical providers accepted 87.5% of pharmacists' antimicrobial recommendations. CONCLUSION: A pharmacist-driven beta-lactam allergy interview was effective in switching eligible patients to beta-lactam therapy and identifying discrepancies between EMR-documented allergies and confirmed allergies. Antimicrobial recommendations were well received by medical providers with a high acceptance rate.

A five-year quasi-experimental study to evaluate the impact of empiric antibiotic order sets on antibiotic use metrics among hospitalized adult patients.

OBJECTIVE: Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase. DESIGN: This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31. SETTING: The study was conducted in a 752-bed tertiary care, academic medical center. INTERVENTION: Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults. RESULTS: For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics. CONCLUSIONS: Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.

Relative Difficulty in the Acquisition of the Phonetic Parameters of Obstruent Coda Voicing: Evidence from Mandarin-Speaking Learners of French.

A recurring finding of research on the L2 acquisition of coda obstruent voicing is that, in terms of the phonetic parameters that serve to realize the voicing contrast, learners are overwhelmingly more accurate with duration than the voicing of the obstruent itself. The current work expands our understanding of this asymmetry in two ways. First, as previous studies have focused almost exclusively on learners of English, we investigate here whether L2 learners' superior production of duration is also found among learners of other target languages via a study of Mandarin-speaking learners' production of French stop and fricative codas. Results from 18 Mandarin-speaking learners of French, primarily of beginner and intermediate proficiency who completed a sentence reading task, parallel those of previous studies with greater accuracy observed for vowel duration than the laryngeal voicing of the obstruent. Second, we explore potential sources of this asymmetry, in particular, the roles of L1 experience as well as of universal factors, namely, the relative perceptual salience of duration versus voicing, and the articulatory difficulty of voicing obstruents.

Articulatory Insights into the L2 Acquisition of English-/l/ Allophony.

In many English varieties, /l/ is produced differently in onsets and codas. Compared with "light" syllable-initial realizations, "dark" syllable-final variants involve reduced tongue tip-alveolar ridge contact and a raised/retracted tongue dorsum. We investigate whether native French and Spanish speakers whose L1 lacks such positionally conditioned variation can acquire English-/l/ allophony, testing the hypotheses that (1) the allophonic pattern will be acquired by both groups but (2) learners will differ from native speakers in their phonetic implementation, particularly in codas; and (3) French-speaking learners will outperform their Spanish-speaking counterparts. The production of syllable-initial and -final /l/ (singletons and clusters) in words read in isolation and a carrier sentence by 4 French- and 3 Spanish-speaking learners as well as three native English speakers was analyzed via electropalatography and acoustic analysis. While some learners produced distinct onset and coda variants and all learners had moved away to some extent from their L1 production, they differed from the native speakers in certain ways. Moreover, between- and within-group variability was observed including greater target-like anterior and posterior contact reduction in codas in the L1 French versus L1 Spanish group and generally higher F2 values in both learner groups compared with their native speaker peers. A comparison of the learners' L1 and L2 production revealed L1-based patterns of positional reduction of the tongue tip and dorsum gestures. We conclude by addressing the contributions of EPG to our understanding of L2 speech and highlight avenues for future research including the study of both linguistic and speaker variables.