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Background: Cefazolin is guideline recommended for perioperative prophylaxis in orthopedic surgery. Despite its unique R1 side chain, cefazolin is often avoided in patients with beta-lactam allergy with concern for cross reactivity. Objectives: The primary outcome was the percentage of patients who received cefazolin perioperatively. Secondary outcomes included the percentage of patients with a beta-lactam allergy clarified following the telephone interview and clinical outcomes including acute kidney injury, surgical site infection, Clostridioides difficile infection, and re-admission at 30 and 90 days. Methods: This single-center, quasi-experimental study evaluated a pilot program in which a pharmacist phoned patients > 18 years of age with a scheduled orthopedic surgery and a documented beta-lactam allergy to assess their allergy preoperatively. Recommendations to use cefazolin were based on an algorithm. Patients were divided into pre- and post-intervention cohorts. Results: A total of 832 patients were screened for inclusion with 135 and 66 patients included in the pre- and post-intervention cohorts. No significant difference was identified in the primary outcome. In the post-intervention cohort, 62% had a beta-lactam reaction updated in the electronic medical record. Those with a beta-lactam allergy delabeled or made less severe were numerically more likely to receive cefazolin than those with an unchanged reaction or a reaction made more severe (95.2% vs 68% vs 65%). There were no differences in clinical outcomes between groups. Conclusion: A pharmacist-conducted preoperative beta-lactam allergy interview in adult patients undergoing elective orthopedic surgery improved beta-lactam allergy documentation but, did not result in increased utilization of cefazolin. [ABSTRACT FROM AUTHOR]

The 1-year longitudinal study presented here examined the extent to which the ability to build phonologically specific lexical entries as a result of increasing vocabulary size predicts word reading via its impact on phonological awareness within and across languages in 62 emerging English (L1) and French (L2) Grade 1 children (M = 75.69 months, SD = 3.18) enrolled in an early French immersion program in Canada. Lexical specificity was assessed with a computerized word learning game in which children were taught new English (e.g., 'foal' and 'sole') and French (e.g., "bac" 'bin' and "bague" 'ring') word pairs contrasted by minimal phonological differences. The results revealed that the specificity of English words at the beginning of Grade 1 predicted English word reading at the end of Grade 1 and that this relationship was mediated by English phonological awareness at the beginning of Grade 1. French lexical specificity at the beginning of Grade 1 did not predict French word reading at the end of Grade 1. Notably, English lexical specificity at the beginning of Grade 1 also predicted French word reading at the end of Grade 1 and this relationship was mediated by English phonological awareness at the beginning of Grade 1. It is concluded that exposure to word pairs involving minimal phonological contrasts fosters phonological awareness, which in turn facilitates word reading within the L1 that then transfers to the L2.

According to Einstein's general theory of relativity, a clock runs more slowly if it is close to a large gravitating object. This principle was highlighted in the movie "Interstellar," in which the main character spends several hours on a planet orbiting a massive black hole, and returns to find that his young daughter has become an elderly woman. In the movie, one hour on the planet equates to seven years on Earth. The same effect can be measured on a much smaller scale by changing locations within Earth's gravitational field. Using atomic clocks, we have compared the ticking of time at Colorado College (elevation 1845 m above sea level), at the United States Air Force Academy (elevation 2165 m), and near the summit of Pikes Peak (elevation 4288 m). Our results confirm that clocks do indeed tick more quickly at higher altitudes, in accordance with Einstein's theory. This work was carried out as a collaboration of physics majors and faculty at Colorado College (CC) and the United States Air Force Academy (USAFA). The experimental technique is straightforward and our results can be reproduced by other students and teachers, given access to an atomic clock and reasonably large changes in elevation. Indeed, a similar endeavor has been reported by amateur clock enthusiasts.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Models such as Eckman's markedness differential hypothesis, Flege's speech learning model, and Brown's feature-based theory of perception seek to explain and predict the relative difficulty second language (L2) learners face when acquiring new or similar sounds. In this paper, we test their predictive adequacy as concerns native English speakers' mastery of French /[image omitted]/ and Spanish /[image omitted]/. Based on an acoustic analysis of the learner data, we demonstrate that these three models do not account for the full range of variability nor for the developmental sequences attested, because they do not consider the degree of difficulty involved in the simultaneous mastery of multiple phonetic parameters across prosodic positions. Consequently, models of L2 phonological acquisition must not only integrate findings from markedness theory and speech perception but also incorporate phonetic constraints on production.

This article seeks to illuminate the degree of position-based variation observed in the acquisition of new segments in a second language and to explain such variability as the consequence of phonetic constraints; this approach contrasts with much previous research that has used typological markedness to the same end. Specifically, it is proposed that learners will have the least difficulty acquiring sounds that involve novel combinations of voicing and manner in positions that favor the phonetic implementation of these sounds. Moreover, on the assumption that not all parameters can be mastered simultaneously, it is predicted that learners will first acquire aspects of a segment's articulation that are perceptually salient and articulatorily easier. The data come from a study of the acquisition of French by 20 intermediate- and advanced-proficiency English-speaking learners of French. Acoustic analysis of the data reveals asymmetries that favor accuracy with manner in onsets versus more targetlike realization of voicing in codas, in which devoicing exists in the input. Beyond demonstrating the role of phonetic principles in determining position-based variation, the findings contribute to our understanding of the acquisition of new consonantal contrasts by providing empirical evidence from a non-Germanic language to bear on this line of inquiry.

Languages differ in the extent to which phonological contrasts observed in onsets are neutralized syllable finally. We examined the acquisition of English syllable-final /m n ŋ/ by L2 learners whose L1 nasal codas lack independent place (Japanese) or neutralize to a single place (Spanish). Three learning outcomes were hypothesized, based on whether learners' production is shaped mainly by coda complexity, perception of the contrast or L1 dialectal realizations. Data from three reading tasks collected from six learners (three of each L1) and two English-speaking controls were examined using electropalatography (EPG). Linguopalatal contact patterns were analyzed quantitatively and qualitatively (presence, absence, and degree of alveolar and velar closures). While difficulty in realizing place contrasts was observed with all L2 speakers, contrary to our hypothesis, the L1 Spanish speakers were less accurate than their Japanese-speaking peers, particularly in the production of word-final prevocalic /ŋ/ for which a high rate of neutralization to /n/ was witnessed. However, the Japanese learners' greater apparent accuracy was due to the presence of non-target final devoiced epenthetic vowels and/or stop-like releases. Overall, the results provide insights into developmental stages in the acquisition of new positional contrasts, including evidence for first language and even idiolectal influence, and highlight the difficulty of blocking L1 neutralization processes. [ABSTRACT FROM AUTHOR]

Study Objective: The preferred antibiotic salvage regimen for persistent methicillin‐resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post‐ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90‐day readmission for MRSAB, 90‐day all‐cause mortality, MRSAB‐related mortality, and incidence of antibiotic‐associated adverse effects. Design: Single‐center, retrospective cohort study between January 1, 2016, and December 31, 2021. Setting: State University of New York Upstate University Hospital, a 748‐bed tertiary care, academic medical center in Syracuse, NY. Patients Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti‐MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated. Measurements and Main Results: Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin‐associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline‐associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post‐ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90‐day readmission for MRSAB. 90‐day all‐cause mortality and MRSAB‐related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively. Conclusions: Vancomycin plus ceftaroline may represent an effective and well‐tolerated salvage regimen option for persistent MRSAB. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The phonetic realization of the English word-final alveolar nasal /n/ is known to be highly variable. Previous articulatory work has reported both gradient and categorical nasal place assimilation including considerable between-speaker differences. This work, however, has largely focused on a small subset of place contexts (namely, preceding velar /k, ɡ/) in a limited number of English varieties. The present article uses electropalatography to study the articulatory realization of /n/ in a wider range of phonetic contexts and read texts as produced by three speakers of Canadian English. The results reveal considerable inter- and intra-speaker differences in the rates of assimilation. Consistent with previous work, we observed a high degree of variation, both gradient and categorical, before velars. Substantial rates of assimilation were also observed before labials, where the process is unexpected from the point of view of gestural phonology but predicted by traditional phonological analyses. The variation in the place and stricture of /n/ before coronals was more limited and typically gradient. Finally, some differences were observed across the text conditions, with more assimilation occurring in carrier sentences than in the read passage and, to a more limited extent, in function than in content words. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Community‐acquired pneumonia (CAP) is a commonly encountered infection and cause of hospitalization. Discontinuation of atypical antibiotic coverage when atypical bacteria are the unlikely cause of CAP represents a potential antimicrobial stewardship opportunity. Study Objective: To compare azithromycin duration, hospital length of stay (LOS), 30‐day all‐cause or pneumonia readmission, and in‐hospital mortality before and after implementation of a pharmacist‐driven azithromycin de‐escalation initiative in the setting of negative laboratory data for atypical bacteria in immunocompetent, nonintensive care unit (non‐ICU) patients treated for CAP. Design Single‐center, quasi‐experimental study. Setting: A 472‐bed academic medical center in Syracuse, NY. Patients Patients were included if they were ≥18 years old, diagnosed with CAP, and had a negative Legionella pneumophila urinary antigen and negative Biofire FilmArray Respiratory Panel for Mycoplasma pneumoniae and Chlamydia pneumoniae. Patients were excluded if they were immunocompromised, admitted to an ICU during hospitalization, prescribed azithromycin for an alternate indication, or had evidence of atypical bacteria. Measurements and Main Results: A total of 983 patients received an azithromycin‐containing regimen for CAP during the study period with 458 and 525 patients in preintervention and postintervention cohorts, respectively. After exclusion criteria were applied, 90 and 100 patients were included in the preintervention and postintervention cohorts, respectively. Demographic and clinical characteristics were mostly similar between cohorts. A statistically significant reduction in azithromycin duration (2 days [interquartile range (IQR) 1‐2.75] vs 5 days [IQR 3‐6], P <.001) and hospital LOS (3 days [IQR 2‐5] vs 5 days [IQR 3‐8.25], P <.001) were observed in the postintervention cohort compared with the preintervention cohort. No statistically significant difference was identified for 30‐day all‐cause 30‐day readmission (15.6% vs 13.0%, P =.614), 30‐day readmission secondary to pneumonia (4.44% vs 2.0%, P =.926), or in‐hospital mortality (1.1% vs 1.0%, P = 1.000) between cohorts. Conclusion: Implementation of a pharmacist‐driven azithromycin de‐escalation initiative for immunocompetent, non‐ICU patients with CAP was associated with a decrease in azithromycin duration and hospital LOS without increasing 30‐day all‐cause or pneumonia readmission, or in‐hospital mortality. [ABSTRACT FROM AUTHOR]

The application of linear regression to data analysis is traditionally a tedious calculation delegated to a computer. This article presents a physical model to facilitate an intuitive way of thinking about the slope of a fit. In this simple model, data points are envisioned as beads applying torques on a massless, rigid, horizontal rod. To illustrate how this model can help colleagues directly address special questions about fits, the model is applied to two situations in which there are repeated measurements of data. This rod-and-bead model also arrives at the coefficient of determination formula in a very straightforward way and makes the recollection of the least-squared slope formula and coefficient of determination much easier. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Study Objective: To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C‐I) or intermittent infusion (I‐I) vancomycin in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics. Design: Single‐center propensity score‐matched retrospective cohort study. Setting: OPAT clinic affiliated with two nearby hospitals. Patients: We identified 300 patients who received C‐I or I‐I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups. Measurements and Main Results: After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22‐fold decrease in nephrotoxicity risk (C‐I 6.8% [5/74 patients] vs I‐I 18.9% [14/74 patients]; odds ratio 3.22, 95% confidence interval 1.10–9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I‐I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C‐I and I‐I groups (13.5% [10/74 patients] vs 23.0% [17/74 patients], p=0.147). Conclusion: In an OPAT setting, C‐I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I‐I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C‐I versus I‐I vancomycin. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation (P =.048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P =.107). Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Articulatory studies have revealed cross-linguistic variation in the realization of cross-word nasal+stop sequences. Whereas languages such as Italian and Spanish show largely categorical regressive place assimilation (Kochetov & Colantoni 2011, Celata et al. 2013), English and German alveolar nasals are often characterized by gradient assimilation, modulated by the degree of overlap with the following gesture (Barry 1991, Ellis & Hardcastle 2002, Jaeger & Hoole 2011). The lack of comparable instrumental studies for French may be due to the common assumption that the language lacks nasal place assimilation in general. We investigate here the production of French /n/+/k ɡ/ sequences via electropalatography. Four female speakers of European and Quebecois French wearing custom 62-electrode acrylic palates read the sentences C'est une bonne casquette 'That's a good cap' and C'est une bonne galette 'That's a good tart/cookie' alongside comparable control sentences involving /n/+/t d/ sequences. For each sequence, assimilation type was determined both qualitatively via visual inspection of the linguopalatal profiles and quantitatively using two contact indices. None of the /n/-tokens exhibited either categorical assimilation (i.e. [ŋk]) or lack of assimilation (i.e. [n(ə)k]). Rather, an intermediate pattern was attested with the nasal involving overlapped coronal and velar gestures ([nn͡ŋ]) and continuous retraction of the constriction. The degree of overlap varied among speakers, extending up to half of the nasal interval. Overall, these French patterns are strikingly different from the categorical processes reported for other Romance languages, yet similar to the gradient assimilation attested in Germanic languages. We conclude by discussing possible sources of these differences. [ABSTRACT FROM AUTHOR]