Etiology and Outcomes of Acute Infectious Conjunctivitis in Children.

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 PCR in cases versus 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 based on 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 PCR. 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.

Evaluation of Antibiotic Use for Dental-Related Infections in Dental Clinics Associated With an Academic Safety Net Institution.

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.

Oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis: a systematic review and meta-analysis of randomized controlled trials.

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.

Oxidative Rearomatization of Tetrahydroisoquinolines Promoted by Pyridine-N-oxide.

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.

HFIP promoted carbo-lactonisation as a new route to functionalised lactones.

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.

Durations of Antibiotic Treatment for Acute Otitis Media and Variability in Prescribed Durations Across Two Large Academic Health Systems.

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.

Secondary household transmission of conjunctivitis in children.

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.

Cost-Effectiveness of Pediatric Conjunctivitis Management and Return to Childcare and School Strategies: A Comparative Study.

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.

Associations with unplanned repeat irrigation and debridement of native septic arthritis.

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.

The Effect of Crystal Arthropathy on the Diagnostic Criteria of Native Septic Arthritis.

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.

Clinical Outcomes Associated with Amoxicillin Treatment for Acute Otitis Media in Children.

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.

Interventions to de-implement unnecessary antibiotic prescribing for ear infections (DISAPEAR Trial): protocol for a cluster-randomized trial.

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.

Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections.

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 ß-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.

Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

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).

Reducing length of antibiotics for children with ear infections: protocol for a cluster-randomized trial in the USA.

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).

Reducing Ophthalmic Antibiotic Use for Non-severe Conjunctivitis in Children.

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.

Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia.

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.).

Reliability of nasopharyngeal PCR for the detection of otopathogens in children with uncomplicated acute otitis media compared to culture.

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.

Metal and Activating Group Free C-4 Alkylation of Isoquinolines via a Temporary Dearomatization Strategy.

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.