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Competing Interests: The authors have no conflicts of interest to disclose.

Objective: To determine the causes of conjunctivitis and whether clinical presentations and outcomes differ by pathogen., Study Design: This multicenter, case-control study enrolled 390 children (194 cases, 196 controls) whose conjunctival samples were tested for bacterial and viral pathogens. Caregivers completed surveys tracking symptoms, antibiotic use, school attendance, and adverse events. The outcomes analyzed included the prevalence of microorganisms detected by polymerase chain reaction in cases vs controls, symptoms, rate of resolution by day 5, school/childcare attendance, and parent-reported antibiotic-related adverse incidents., Results: Most cases (148, 76%) and controls (112, 57%) had bacteria identified, although only detection of Haemophilus influenzae was associated with conjunctivitis (aOR 4.59, 95% CI 2.86, 7.37). Purulent discharge was associated with H influenzae (aOR 2.47, 95% CI 1.23, 5.01) and occurred in 92 (77%) cases in which H influenzae was detected and 39 (53%) in which H influenzae was not detected. Improvement (186, 96%) and resolution (166, 86%) were observed by day 5 for most children and did not differ on the basis of ophthalmic antibiotic use. Caregivers reported antibiotic-associated adverse events for 21 (20%) children, with 8 (8%) requiring a medical visit., Conclusions: Only H influenzae was significantly associated with conjunctivitis. Symptoms did not differ in children with or without bacteria detected by polymerase chain reaction. Independent of antibiotic use, most children experienced resolution by day 5, but parents reported adverse events in 20% of children treated with topical antibiotics, underscoring the importance of judicious prescribing., Competing Interests: Declaration of Competing Interest This work was funded by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under award number K23HD099925. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health. The authors have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Isoquinolines are ubiquitous arenes found in many biologically useful molecules. While direct substitution at the heterocyclic ring is uncommon, reductive functionalization to form tetrahydroisoquinolines (THIQs) is straightforward. Herein, we describe a facile method for producing C4-functionalized isoquinolines from a readily available parent THIQ. This high-temperature transformation utilizes pyridine- N -oxide as an oxidant generating only volatile side products and is functional-group-tolerant.

Background: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system., Methods: Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a diagnosis of AOM from 2019 to 2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for nonfirst-line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events., Results: Among 73 198 AOM encounters for children 2 years and older, 61 612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45 689; 75%), 20% were for 7 days (12 060), and only 5% were for 5 days (3144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent-care visits for AOM within 30 days after the index visit were rare., Conclusions: Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

This retrospective study found lower antibiotic prescribing rates by outpatient dentists than previous literature, but with deviations from guideline recommendations in antibiotic indications and durations of treatment for oral pain and swelling. These findings will guide future stewardship interventions to promote guideline-directed therapy plans., Competing Interests: Potential conflicts of interest. The authors: no reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We conducted a systematic review of randomized controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis., Methods: MEDLINE, EMBASE, the Cochrane Library, and Web of Science database were searched through February 21st, 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with the Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis. (PROSPERO CRD42024481512)., Results: Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between the oral and intravenous therapy groups (RR 0.99; 95% CI, 0.63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR 0.65; 95% CI, 0.07-5.94; I2 = 74%); however, the confidence interval is wide, and heterogeneity was high., Conclusions: In this systematic review of RCTs comparing oral to intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We have been able to induce a series of lactonisation reactions of unsaturated acids using a carbocationic intermediate formed in situ . The transformation generates five and six membered lactone rings AND forms a new exocyclic C-C bond at the same time, thus removing the need for further derivatisation of typical lactonisation products (such as from iodo lactonisation). The reaction is operationally straightforward, does not employ any metals and utilises readily accessible alcohol and unsaturated acid substrates.

Among surveyed households, the transmission rate of pediatric conjunctivitis was 12%. Rates did not differ when the index child did or did not use an ophthalmic antibiotic (14% vs 11% [P = 0.6]). Transmission rates were lower than for other infections where children are not routinely excluded from school or daycare., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Infectious conjunctivitis affects 1 in 8 children annually, resulting in high ophthalmic antibiotic prescribing and absenteeism from childcare and school. We aimed to quantify the cost-effectiveness and annual savings of 3 evidence-based approaches to conjunctivitis management and return to childcare and school compared to usual care., Methods: Using a decision analytic model from a societal perspective over a 1-year time horizon, we conducted a cost-effectiveness analysis of 3 management strategies for children aged 6 months to 17 years with non-severe conjunctivitis compared to usual care in the United States. Strategies accounted for rate of transmission. Strategies included (1) refraining from prescribing ophthalmic antibiotics for non-severe conjunctivitis, (2) allowing children without systemic symptoms to attend childcare and school, (3) and the combined approach of refraining from prescribing ophthalmic antibiotics and allowing children without systemic symptoms to attend childcare and school., Results: The estimated annual expenditure for pediatric conjunctivitis was $1.95 billion. Usual care was the most expensive ($212.73/episode), followed by refraining from ophthalmic antibiotic prescribing ($199.92) and allowing children without systemic symptoms to attend childcare and school ($140.18). The combined approach was the least costly ($127.38). Disutility was similar between approaches (quality-adjusted life days 0.271 vs 0.274). Refraining from antibiotic prescribing and the combination approach were dominant compared to usual care. The combined approach resulted in an estimated $783 million annual savings and 1.6 million ophthalmic antibiotic courses averted., Conclusions: Conjunctivitis poses an economic burden that could be reduced by refraining from ophthalmic antibiotic use and allowing children without systemic symptoms to remain at school or childcare., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Distinguishing between septic arthritis and crystal arthropathy flares can be challenging. The purpose of this study was to determine how the presence of synovial crystals affects the diagnostic criteria of septic arthritis., Methods: A retrospective review identified patients undergoing joint aspirations to rule out native septic arthritis. Differences between septic arthritis presenting with and without synovial crystals were analyzed. A receiver-operating characteristic curve was plotted for laboratory markers to determine the area under the curve, or diagnostic accuracy, for septic arthritis and to evaluate thresholds that maximized sensitivity and specificity., Results: There were 302 joint aspirations in 267 patients. Septic arthritis was diagnosed in 17.9% (54/302). Patients with synovial crystals were less likely to have septic arthritis (4.2% [5/119] vs. 26.8% [49/183], P < 0.0001). Septic arthritis in patients with no synovial crystals was associated with fever and a higher synovial white blood cell (WBC) count, synovial polymorphonuclear cell percentage (PMN%), serum WBC, and C-reactive protein (CRP) ( P < 0.05). Septic arthritis in patients with synovial crystals was only associated with inability to bear weight and a higher synovial WBC and CRP ( P < 0.05). Synovial PMN% was considered nondiagnostic of septic arthritis (area under the curve 0.56) in patients with crystals while synovial WBC and CRP had acceptable (0.76) and excellent (0.83) diagnostic utility, respectively. The WBC and CRP value thresholds that maximized sensitivity and specificity for septic arthritis were greater in patients with crystals (21,600 vs. 17,954 cells/μL and 125 vs. 69 mg/L, respectively)., Discussion: The presence of synovial crystals reduced the likelihood of septic arthritis and altered the laboratory diagnostic criteria. PMN% was nondiagnostic in the setting of synovial crystals., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Purpose: To identify associations with unplanned repeat irrigation and debridement (I&D) after arthrotomy for native septic arthritis., Methods: A retrospective review identified patients with native septic arthritis treated with open arthrotomies. The primary outcome was unplanned repeat I&D within 90 days. Associations evaluated for included comorbidities, ability to bear weight, fever, immunosuppressed status, purulence, C-reactive protein, erythrocyte sedimentation rate, white blood cell count (synovial fluid and serum levels), and synovial fluid polymorphonuclear cell percentage (PMN%)., Results: There were 59 arthrotomies in 53 patients involving the knee (n = 32), shoulder (n = 10), elbow (n = 8), ankle (n = 6), and hip (n = 3). The median patient age was 52, and a 71.2% were male. An unplanned repeat I&D was required in 40.7% (n = 24). The median time to the second I&D was 4 days (interquartile range 3 to 9). On univariate analysis, unplanned repeat I&Ds were associated with fever (p = 0.03), purulence (p = 0.01), bacteria growth on cultures (p = 0.02), and the use of deep drains (p = 0.05). On multivariate analysis, the only variables that remained associated with unplanned repeat I&Ds were fever (odds ratio (OR) 5.5, 95% confidence interval (CI) 1.3, 23.6, p = 0.02) and purulence (OR 5.3, CI 1.1, 24.4, p = 0.03)., Conclusions: An unplanned repeat I&D was required in 40.7% of patients and was associated with fever and purulence. These findings highlight the difficulty of controlling these infections and support the need for future research into better methods of management., Level of Evidence: Diagnostic, Level III., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production., Methods: 205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE)., Results: 8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05)., Conclusions: Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days)., Competing Interests: Potential conflicts of interest. E. K. M. reports consulting fees for Advisory Boards from AbbVie, Merck, Shionogi, Cidara, Ferring, Summit, La Jolla, Venatorx, Entasis, LabSimply, and Basilea; participation on DSMB for Wockhardt and on DMBD for A Phase I, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Ertapenem in Combination with Zidebactam (WCK 6777) in Healthy Adult Subjects; speaking honorarium for UTI symposium at ECCMID 2023 from GlaxoSmithKlein (GSK) and speaking honorarium for COVID-19 symposium at IDWeek 2022; travel support to attend ECCMID 2023 from GSK. E. S. has received grant funding from Merck & Co and bioMérieux, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Watchful waiting management for acute otitis media (AOM), where an antibiotic is used only if the child's symptoms worsen or do not improve over the subsequent 2-3 days, is an effective approach to reduce antibiotic exposure for children with AOM. However, studies to compare the effectiveness of interventions to promote watchful waiting are lacking. The objective of this study is to compare the effectiveness and implementation outcomes of two pragmatic, patient-centered interventions designed to facilitate use of watchful waiting in clinical practice., Methods: This will be a cluster-randomized trial utilizing a hybrid implementation-effectiveness design. Thirty-three primary care or urgent care clinics will be randomized to one of two interventions: a health systems-level intervention alone or a health systems-level intervention combined with use of a shared decision-making aid. The health systems-level intervention will include engagement of a clinician champion at each clinic, changes to electronic health record antibiotic orders to facilitate delayed antibiotic prescriptions as part of a watchful waiting strategy, quarterly feedback reports detailing clinicians' use of watchful waiting individually and compared with peers, and virtual learning sessions for clinicians. The hybrid intervention will include the health systems-level intervention plus a shared decision-making aid designed to inform decision-making between parents and clinicians with best available evidence. The primary outcomes will be whether an antibiotic was ultimately taken by the child and parent satisfaction with their child's care. We will explore the differences in implementation effectiveness by patient population served, clinic type, clinical setting, and organization. The fidelity, acceptability, and perceived appropriateness of the interventions among different clinician types, patient populations, and clinical settings will be compared. We will also conduct formative qualitative interviews and surveys with clinicians and administrators, focus groups and surveys of parents of patients with AOM, and engagement of two stakeholder advisory councils to further inform the interventions., Discussion: This study will compare the effectiveness of two pragmatic interventions to promote use of watchful waiting for children with AOM to reduce antibiotic exposure and increase parent satisfaction, thus informing national antibiotic stewardship policy development., Clinical Trial Registration: NCT06034080., (© 2024. The Author(s).)

Importance: Management of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable., Objective: To examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs., Design, Setting, and Participants: A retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023., Exposures: Administration of antibiotics for GN-BSIs., Main Outcomes and Measures: Baseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed., Results: Of a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by β-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics., Conclusions and Relevance: In this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

As spinal cord stimulation (SCS) becomes a staple of chronic pain management, the SCS industry must constantly evolve to ensure safety, convenience and enhanced efficacy. Beyond waveforms and size, MR-conditionality is a key differentiator sought out by physicians and patients when choosing SCS devices. Many common SCS complications, including lead migration, can affect the MR-conditionality. The authors reviewed literature published between 2015 and 2024 using PubMed and Google Scholar databases, as well as US FDA labels for magnetic resonance imaging and technical manuals with further confirmation from local representatives. Through extensive review of the literature and direct extraction from each SCS device company, the authors aimed to investigate the specific terms of MR-conditionality under various circumstances. This article provides a collective reference of the MR-conditionality of the currently available SCS devices under normal conditions, as well as with common failure modes, such as lead migration, lead fracture and battery detachment.

Aim: Preventing unnecessarily long durations of antibiotic therapy is a key opportunity to reduce antibiotic overuse in children 2 years of age and older with acute otitis media (AOM). Pragmatic interventions to reduce durations of therapy that can be effectively scaled and sustained are urgently needed. This study aims to fill this gap by evaluating the effectiveness and implementation outcomes of two low-cost interventions of differing intensities to increase guideline-concordant antibiotic durations in children with AOM. Methods: The higher intensity intervention will consist of clinician education regarding guideline-recommended short durations of antibiotic therapy; electronic health record (EHR) prescription field changes to promote prescribing of recommended short durations; and individualized clinician audit and feedback on adherence to recommended short durations of therapy in comparison to peers, while the lower intensity intervention will consist only of clinician education and EHR changes. We will explore the differences in implementation effectiveness by patient population served, clinician type, clinical setting and organization as well as intervention type. The fidelity, feasibility, acceptability and perceived appropriateness of the interventions among different clinician types, patient populations, clinical settings and intervention type will be compared. We will also conduct formative qualitative interviews with clinicians and administrators and focus groups with parents of patients to further inform the interventions and study. The formative evaluation will take place over 1.5 years, the interventions will be implemented over 2 years and evaluation of the interventions will take place over 1.5 years. Discussion: The results of this study will provide a framework for other healthcare systems to address the widespread problem of excessive durations of therapy for AOM and inform national antibiotic stewardship policy development. Clinical Trial Registration : NCT05608993 (ClinicalTrials.gov).

Background: Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus ., Methods: In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed., Results: Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole., Conclusions: Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated S. aureus bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.)., (Copyright © 2023 Massachusetts Medical Society.)

Otopathogens in acute otitis media (AOM) have implications for care because the likelihood of resolution without antibiotics and optimal antibiotic agent varies by microorganism. We aimed to determine the sensitivity, specificity, positive predictive value, and negative predictive value of nasopharyngeal (NP) qualitative polymerase chain reaction (PCR) for common bacterial otopathogens in children with AOM compared to NP culture. NP flocked swabs collected from enrolled children aged 6 to 35 months with uncomplicated AOM in Denver, CO were tested by culture and multiplex PCR. The sensitivity and negative predictive value of PCR using culture as a reference were high (H. influenzae 93.3%, 98.0%; S. pneumoniae 94.2%, 95.1%; M. catarrhalis 92.3%, 86.4%); whereas the specificity and positive predictive value were lower and varied by organism (54.2%-84.1%, 55.1%-69.2%, respectively). PCR detected 1.5 times more organisms than culture. NP PCR has a high predictive value for excluding otopathogens compared to culture and warrants exploration as a diagnostic tool., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HF serves as a senior scientific advisor for QuidelOrtho and holds a patent for diagnosing and treating otitis media #63/335,801. QuidoOrtho had no role in the design or interpretation of the study and Quidel staff were blinded to culture results. SD serves as a consultant and receives grant support from Biofire, serves as a consultant for Karius, and receives grant support from Pfizer for projects not pertaining to this project., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Antibiotics are often overprescribed for pediatric conjunctivitis. We implemented a system-level quality improvement (QI) intervention to reduce unnecessary ophthalmic antibiotic use., Methods: The multi-faceted intervention in Denver, CO comprised a clinical care pathway, nurse protocol modifications, electronic health record (EHR) changes, parent education materials, and clinician education. We evaluated children aged 6 months-17 years with conjunctivitis seen between November 2018 and December 2022. A multi-interrupted time series model evaluated the effectiveness of the intervention over three time periods: Pre-COVID, Pre-Intervention (November 2018-February 2020), COVID, Pre-Intervention (March 2020-March 2021), and Post-Intervention (April 2021-December 2022). Fisher's exact tests compared treatment failure and healthcare utilization rates between time periods and among children receiving or not receiving ophthalmic antibiotics., Results: Among 6960 eligible encounters, ophthalmic antibiotic use was reduced by 18.8% (95% CI: 16.3, 21.3) from Pre-COVID, Pre-Intervention to Post-Intervention. During the Pre-Intervention period following the onset of COVID, a reduction of 16.1% (95% CI: 12.9, 19.3) was observed. Implementation of the intervention resulted in an additional 2.7% (95% CI: -0.4, 5.7) reduction in antibiotic prescribing, primarily in younger children (ages 6 months-5 years). The greatest reduction in prescribing occurred for nurse triage encounters with an 82.1% (95% CI: 76.8, 87.5) reduction in prescribing rates (92.6%-10.5%). Treatment failure occurred in 1301 (18.7%) children and was more common among children that received an ophthalmic antibiotic than those that did not (20.0 vs 17.9%; P = .03)., Conclusion: The QI intervention significantly reduced ophthalmic antibiotic prescribing for pediatric conjunctivitis without increasing treatment failure rates or health care utilization., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this study was to assess the effects of feeding gelatin capsules containing fish oil, treated with alcoholic solutions of flavoring agents followed by drying, on lactation performance, rumen fatty acids content and milk enrichment of fatty acids. In Trial 1, four multiparous ruminally fistulated Holstein cows were randomly assigned to one of four dietary treatments sequences in a 4 × 4 Latin square design. Treatments consisted of (1) Control with no capsules, (2) Control plus 200 untreated capsules per cow/day, mixed with the TMR, (3) Control plus 200 treated capsules per cow/day placed directly into the rumen, (4) Control plus 200 treated capsules per cow/day, mixed with the TMR. In Trial 2, three fistulated Holstein and three fistulated Jersey multiparous cows were randomly assigned to three dietary treatments sequences in a replicated 3 × 3 Latin square design. Treatments consisted of (1) Control with no capsules fed to the cows, (2) Control plus 180 untreated capsules per cow/day, (3) Control plus 180 treated capsules per cow/day. Compared to control, feeding fish oil capsules significantly (Trial 1) or numerically (Trial 2) reduced milk fat concentration and yield. Furthermore, in both trials, the feeding of untreated or treated capsules had no effect on animal performance or milk composition. In both trials, compared to controls, supplementing the diet with fish oil capsules consistently increased total trans C18:1 isomers and DHA concentration in the rumen and milk fat. However, for both trials, capsule protection treatment had a minimal effect on the concentration of any of the reported rumen and milk fatty acids. When assessed under laboratory control conditions, due to water absorption, the treated capsule weight was increased by 40% while resistance to pressure decreased by 84% after 2 h of incubation in water. The results of this study suggest that due to a reduction in the capsule shell's resistance to abrasion, treated capsules marginally prevented the release of fish oil in the rumen.

A simple method for the C-4 alkylation of isoquinolines is described using benzoic acid as a nucleophilic reagent and vinyl ketones as an electrophile. The reaction shows tolerance for substitution at C-3, and C-5-C-8 positions as well as allowing some variation of the vinyl ketone electrophiles. The products contain a carbonyl that can act as a synthetic handle for further manipulations giving esters, amines, or simple alkyl products.

Background: Acute uncomplicated cystitis is common among outpatients and frequently leads to antibiotic prescriptions, making urinary tract infections (UTIs) an important area for antimicrobial stewardship initiatives. Infectious Disease Society of America (IDSA) guidelines promote alternative agents in place of fluoroquinolones for acute uncomplicated cystitis. Despite IDSA guidance, adherence to the guideline remains low in the United States (US). Several studies have described interventions to improve guideline-concordant prescribing for UTIs. However, the long-term sustainability and impact of fluoroquinolone (FLQ)-sparing strategies on community antimicrobial resistance and treatment outcomes are unknown. The objectives of this study were to characterize current antibiotic prescribing patterns, treatment failures and Escherichia coli resistance rates in a setting which instituted FLQ sparing strategies for UTIs in 2007., Methods: Retrospective cohort study of women aged ⩾ 18 diagnosed with acute uncomplicated cystitis based on International Classification of Diseases, 10th Revision (ICD-10) codes were included. Data were abstracted for ambulatory visits over a 6-month period, January 2018 to June 2018, at a large urban health care system. Treatment decisions were made by individual providers, and data were analyzed retrospectively. Nitrofurantoin (NFT) resistance was obtained from the institutional antibiogram and patient-level data. Treatment failure was defined as the need for a different antibiotic for UTI within 28 days of the original prescription., Results: NFT was the most frequently prescribed antibiotic ( n  = 386, 71.6%) of empiric antibiotic prescriptions for UTIs. FLQs comprised 4.6% of all antibiotic prescriptions ( n  = 25). Treatment failure rate was 2.3% in patients treated with NFT. Urine culture was ordered for only 26.8% of patients. Among the small group of patients with cultures ordered, E. coli remained 98.5% susceptible to NFT., Conclusions: This study is the first to report significantly low rates (4.6%) of FLQ prescribing for acute uncomplicated cystitis. Treatment failure rate was low with empiric NFT. Increased NFT resistance among E. coli was not observed at the institution or among the subset of patients with E. coli positive urine cultures. These findings support current IDSA treatment guidance for uncomplicated cystitis., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial., Methods: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality., Results: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality., Conclusions: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The association of SARS-CoV-2 with acute otitis media (AOM) in children is poorly understood., Methods: Cases were identified as a subpopulation within the NO TEARS prospective AOM study in Denver, CO from March to December 2020. Children enrolled were 6 to 35 months of age with uncomplicated AOM; those with AOM and SARS-CoV-2 were included. Data was obtained from electronic medical records and research case report forms., Results: A total of 108 patients enrolled in the NO TEARS study from May 2019 through December 2020 (all subsequently tested for SARS CoV-2). During the COVID-19 pandemic study period (March-December 2020), 16 patients enrolled, and 7 (43.6%) were identified with AOM/COVID-19 co-infection. Fever was present in 3 of 7 children (29%). Four children (57%) attended daycare. Only 2 children (29%) had SARS CoV-2 testing as part of their clinical workup. Mean AOM-SOS © scores were similar among SARS CoV-2 positive and negative patients with no statistical significance with two-sided t -tests: 13.6 (±4.5) versus 14.2 (±4.9) at enrollment, 1.4 (±1.8) versus 4.2 (±4.9) on Day 5, and 0.6 (±0.9) versus 2.5 (±6.1) on Day 14. Among the 7 cases, no child had an AOM treatment failure or recurrence within 3 to 14 or 15 to 30 days respectively. Of the 6 patients with completed bacterial and viral testing, a bacterial pathogen was identified in all 6, and a viral pathogen in 3 (50%)., Conclusions: COVID-19 and AOM can co-exist. Providers should maintain a high index of suspicion for COVID-19 even in patients with clinical AOM and should not use a diagnosis of AOM to exclude COVID-19.

Objective: To compare the effectiveness of 2 interventions in improving prescribing of guideline-concordant durations of therapy for acute otitis media (AOM)., Study Design: This was a quasi-experimental mixed methods analysis that compared a bundled quality improvement intervention consisting of individualized audit and feedback, education, and electronic health record (EHR) changes to an EHR-only intervention. The bundle was implemented in 3 pediatric clinics from January to August 2020 and an EHR-only intervention was implemented in 6 family medicine clinics. The primary outcome measure was prescription of an institutional guideline-concordant 5-day duration of therapy for children ≥2 years of age with uncomplicated AOM. Propensity score matching and differences-in-differences analysis weighted with inverse probability of treatment were completed. Implementation outcomes were assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance Framework. Balance measures included treatment failure and recurrence., Results: In total, 1017 encounters for AOM were included from February 2019 to August 2020. Guideline-concordant prescribing increased from 14.4% to 63.8% (difference = 49.4%) in clinics that received the EHR-only intervention and from 10.6% to 85.2% (difference = 74.6%) in clinics that received the bundled intervention. In the adjusted analysis, the bundled intervention improved guideline-concordant durations by an additional 26.4% (P < .01) compared with the EHR-only intervention. Providers identified EHR-prescription field changes as the most helpful components. There were no differences in treatment failure or recurrence rates between baseline and either intervention., Conclusions: Both interventions resulted in improved prescribing of guideline-concordant durations of antibiotics. The bundled intervention improved prescribing more than an EHR-only intervention and was acceptable to providers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Infectious conjunctivitis is among the most common pediatric infections worldwide; antibiotics are often not indicated. We aimed to determine factors associated with ophthalmic antibiotic prescribing and changes in prescribing prior to and during the COVID-19 pandemic at a single center., Methods: Encounters for children with infectious conjunctivitis from 2017 to 2020 at Denver Health and Hospital Authority clinics were analyzed retrospectively. Factors associated with prescribing were evaluated using multivariable logistic regression modeling. Encounter numbers and prescribing patterns for telephone versus in-person visits before and during the pandemic were compared and stratified., Results: Of 5,283 patients encounters for conjunctivitis, 3,841 (72.7%) resulted in an ophthalmic antibiotic prescription. Concurrent diagnosis with acute otitis media (adjusted odds ratio [aOR] 0.20 (95% CI, 0.16-0.25) and later study year (2018-aOR = 0.76 [95% CI, 0.65-0.89]; 2019- aOR = 0.57 [95% CI, 0.48-0.67]) were associated with reduced odds of prescribing. Compared with those evaluated in pediatric clinics, patients evaluated in family medicine (aOR = 0.69 [95% CI, 0.58-0.83]) or optometry/ophthalmology clinics (aOR = 0.06 [95% CI, 0.02-0.14]) were less likely to have antibiotics prescribed, whereas, patients evaluated via telephone had a 5.43 (95% CI, 3.97-7.42) greater odds of being prescribed ophthalmic antibiotics. Antibiotic prescribing increased from 67.8% prior to the COVID-19 pandemic to 81.9% during the pandemic (P < 0.0001)., Conclusions: Discordant with national guideline recommendations, ophthalmic antibiotic use for conjunctivitis was high. Telephone visits were associated with higher rates of prescribing. Rates of prescribing increased significantly during the COVID-19 pandemic., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions., Methods: Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds., Results: Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable., Conclusions: In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Across the ambulatory care network of an integrated health care system, durations of antibiotic therapy prescribed for uncomplicated infections were longer than recommended in 39% of cases. By logistic regression, site of care, prescriber characteristics, and type of infection were independently associated with longer than recommended durations of therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

United States guidance for hospital antibiotic stewardship has emphasized prospective audit and feedback and prior authorization of select antibiotics as core interventions. These remain the most common interventions implemented by stewardship programs. Although these approaches have been shown to reduce unnecessary antibiotic use, they incorrectly put the onus for appropriate antibiotic use on the stewardship team rather than the prescribing clinician. We propose that a primary focus of stewardship programs should be implementation of broader interventions that engage frontline clinicians and equip them with tools to integrate antibiotic stewardship into their own daily practice, thus reducing the need for day-to-day stewardship team oversite. We discuss a framework of broader interventions and policies that will facilitate this paradigm shift., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Surveyed caregivers of children in Denver, Colorado, with acute otitis media (AOM) preferred immediate antibiotics over delayed antibiotics or observation. Overall, 77% stated that they would immediately fill a prescription written as delayed. In contrast, 86% of caregivers favored whichever duration was recommended by the provider or the shortest duration necessary., Competing Interests: Conflicts of Interest. All authors report no conflicts of interest relevant to this article.

Background: National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics., Methods: This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration., Results: Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001)., Conclusions: Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Twenty-seven patients receiving prolonged inpatient antibiotic therapy for a serious bacterial infection received a single dose of dalbavancin 7-10 days before the planned end date to facilitate earlier hospital discharge. Eighty-one percent met criteria for clinical success, 7% experienced a potential adverse event, and 182 hospital days were averted., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To determine the frequency that non-first-line antibiotics, safety-net antibiotic prescriptions (SNAPS), and longer than recommended durations of antibiotics were prescribed for children ≥2 years of age with acute otitis media and examine patient and system level factors that contributed to these outcomes., Study Design: Children age ≥2 years with acute otitis media seen at Denver Health Medical Center outpatient locations from January to December 2018 were included. The percentages of patients who received first-line antibiotics, SNAPs, and recommended durations of antibiotics were determined. Factors associated with non-first-line and longer than recommended antibiotic durations were evaluated using multivariate logistic regression modeling., Results: Of the 1025 visits evaluated, 98.0% were prescribed an antibiotic; only 4.5% of antibiotics were SNAPs. Non-first-line antibiotics were prescribed to 18.8% of patients. Most antibiotic durations (94.1%) were longer than the institution recommended 5 days and 54.3% were ≥10 days. Private insurance was associated with non-first-line antibiotics (aOR, 1.89; 95% CI, 1; 14-3.14, P = .01). Patients who were younger (2-5 years; aOR 2.01; 95% CI, 1.32-3.05; P < .001) or seen in emergency/urgent care sites (aOR, 1.73; 95% CI, 1.26-2.38; P < .001) were more likely to receive ≥10 days of antibiotic compared with those in pediatric clinics., Conclusions: Antibiotic stewardship interventions that emphasize the duration of antibiotic therapy as well as the use of SNAPs or observation may be higher yield than those focusing on first-line therapy alone. Numerous system and patient level factors are associated with off-guideline prescribing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Antibiotic overuse remains a significant problem. The objective of this study was to develop a methodology to evaluate antibiotic use across inpatient and ambulatory care sites in an integrated healthcare system to prioritize antibiotic stewardship efforts., Methods: We conducted an epidemiologic study of antibiotic use across an integrated healthcare system on 12 randomly selected days from 2017 to 2018. For inpatients and perioperative patients, administrations of antibiotics were recorded, whereas prescriptions were recorded for outpatients., Results: On the study days, 10.9% (95% confidence interval [CI], 10.6%-11.3%) of patients received antibiotics. Of all antibiotics, 54.1% were from ambulatory care (95% CI, 52.6%-55.7%), 38.0% were from the hospital (95% CI, 36.6%-39.5%), and 7.8% (95% CI, 7.1%-8.7%) were perioperative. The emergency department/urgent care centers, adult outpatient clinics, and adult non-critical care inpatient wards accounted for 26.4% (95% CI, 25.0%-27.7%), 23.8% (95% CI, 22.6%-25.2%), and 23.9% (95% CI, 22.7%-25.3%) of antibiotic use, respectively. Only 9.2% (95% CI, 8.3%-10.1%) of all antibiotics were administered in critical care units. Antibiotics with a broad spectrum of gram-negative activity accounted for 30.4% (95% CI, 29.0%-31.9%) of antibiotics. Infections of the respiratory tract were the leading indication for antibiotics., Conclusions: In an integrated healthcare system, more than half of antibiotic use occurred in the emergency department/urgent care centers and outpatient clinics. Antibiotics with a broad spectrum of gram-negative activity accounted for a large portion of antibiotic use. Analysis of antibiotic utilization across the spectrum of inpatient and ambulatory care is useful to prioritize antibiotic stewardship efforts., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We surveyed emergency department and urgent care clinicians to assess patterns of use and perceived usefulness of a local antibiotic stewardship application to deliver institution-specific prescribing guidance. Among 114 eligible respondents, the application was widely utilized, and it was perceived to be a useful clinical resource that improved prescribing.

Diet-induced milk fat depression (MFD) is a multifactorial disorder that can be triggered by a variety of conditions. Feeding high amounts of starch and unsaturated fatty acids has been shown to reduce milk fat yield and composition, as well as alter ruminal biohydrogenation patterns. However, little is known about how starch degradability in the rumen influences recovery from diet-induced MFD and if production of milk fat-inhibiting isomers will persist following an episode of MFD. The objective of this study was to evaluate production performance and ruminal fermentation in cows recovering from MFD when corn with a low or high starch degradability is fed. Six ruminally fistulated Holstein cows were used in a crossover design with 2 periods. During each period, MFD was induced for 10 d by feeding a diet with low fiber, high starch, and high unsaturated fatty acid. The polyunsaturated fatty acid concentration of the diet during the induction phase was modified primarily through inclusion of soybean oil. Following induction, cows were switched to either a high degradable starch recovery diet (HDS) or a low degradable starch recovery diet (LDS) for 18 d. The 7-h starch degradability was 66.5% for LDS and 87.8% for HDS. Milk was collected every 3 d for component and fatty acid analysis. On d 0, 4, 7, 10, 16, 22, and 28 of each period, ruminal pH and rumen fluid were collected every 2 h. Milk fat yield and composition was reduced during MFD induction and progressively increased by day in both HDS and LDS during recovery. Dry matter intake was similar among treatments and increased steadily over time during recovery. Preformed fatty acids were greater for HDS-fed animals, and de novo fatty acid in milk fat was greater for LDS-fed animals. Milk trans-10 C18:1 tended to be greater for HDS, and trans-10,cis-12 conjugated linoleic acid was significantly greater for HDS. cis-9,trans-11 conjugated linoleic acid was not affected by starch degradability during recovery. Total volatile fatty acids, butyrate, and valerate tended to differ or differed with recovery treatment, but ruminal pH and ammonia concentration were unaffected. The HDS diet responded similarly to the LDS diet during recovery with regard to milk fat percentage, but milk and fat yield tended to consistently be lower in HDS. When considering approaches to ameliorate diet-induced MFD, the degradability of the starch within rations should be evaluated. Although animal performance was similar, some trans fatty acid isomers were persistent in the milk through the recovery phase with HDS-fed animals, suggesting that milk fat synthesis might be potentially inhibited and biohydrogenation pathways modified in the rumen following an episode of MFD., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Colorado hospitals participated in a statewide collaborative to improve the management of inpatient urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). We evaluated the effects of the intervention on diagnostic accuracy and antibiotic use., Methods: The main collaborative outcomes were proportion of UTI diagnoses that met criteria for symptomatic UTI; exposure to fluoroquinolones (UTI only); duration of therapy (UTIs and SSTIs); and exposure to antibiotics with broad gram-negative activity (SSTIs only). Outcomes were compared between pre-intervention and intervention periods overall and by hospital. Secondary analyses were changes in outcome trends by time series analysis., Results: Twenty-six hospitals, including 9 critical access hospitals, participated in the collaborative. Data were reported for 4060 UTIs and 1759 SSTIs. Between the pre-intervention and intervention periods, the proportion of diagnosed UTIs that met criteria for symptomatic UTI was similar (51% vs 54%, respectively; P = .10), exposure to fluoroquinolones declined (49% vs 41%; P < .001), and the median duration of therapy was unchanged (7 vs 7 days; P = .99). Among SSTIs, exposure to antibiotics with broad gram-negative activity declined (61% vs 53%; P = .001) and the median duration of therapy declined (11 vs 10 days; P = .03). There was substantial variation in performance among hospitals. By time series analysis, only the declining trend of fluoroquinolone use was significant (P = .03)., Conclusions: The collaborative model is a feasible approach to engage hospitals in a common antibiotic stewardship intervention. Performance improvement was observed for several outcomes but varied substantially by hospital.

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown., Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events., Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization., Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care., Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia., Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6])., Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm., Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.

We evaluated the appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis. Overall, 81% of antibiotic prescriptions for acute sinusitis were inappropriate and 48% of antibiotic prescriptions for pharyngitis were inappropriate. Types of prescribing errors differed between the 2 infections, including lack of an indication for antibiotics and excessive duration in ~50% of sinusitis cases and incorrect antibiotic dose in ~33% of pharyngitis cases.Infect Control Hosp Epidemiol 2018; 0, 1-3.

Smartphones are increasingly used to access clinical decision support, and many medical applications provide antimicrobial prescribing guidance. However, these applications do not account for local antibiotic resistance patterns and formularies. We implemented an institution-specific antimicrobial stewardship smartphone application and studied patterns of use over a 1-year period.

Background: The objective of this study was to characterize treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and describe the association between hospital admission and emergency department (ED) visits or readmissions within 30 days after initial episode of care (IEC)., Methods: This was a retrospective, observational, cohort study of adults with ABSSSI who presented to an ED between July 1, 2012, and June 30, 2013. Patient, health care facility, and treatment characteristics, including unplanned ED visits or readmissions, were obtained through manual chart review and abstraction. Adjusted logistic regression analysis examined likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients., Results: Records from 1527 ED visits for ABSSSI from 40 centers were reviewed (admitted, n = 578 [38%]; nonadmitted, n = 949 [62%]). Admitted patients were typically older (mean age, 52.2 years vs 43.0 years), more likely to be morbidly obese (body mass index > 40 kg/m 2 ; 17.3% vs 9.1%), and had more comorbidities (Charlson Comorbidity Index ≥ 4; 24.4% vs 6.8%) compared with those not admitted. In the primary analysis, adjusted logistic regression, controlling for comorbidities and severity of illness, demonstrated that there was a similar likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients (odds ratio, 1.03; 95% confidence interval, 0.74-1.43; P = .87)., Conclusions: ABSSSI treatment pathways leveraging outpatient treatment vs hospital admission support similar likelihood of unplanned 30-day ED visits or readmissions, an important clinical outcome and quality metric at US hospitals. Further research regarding the decision criteria around hospital admission to avoid potentially unnecessary hospitalizations is warranted.