Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Protocol and statistical analysis plan for the Antibiotic Choice On ReNal outcomes (ACORN) randomised clinical trial.

INTRODUCTION: Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin-tazobactam) is associated with acute kidney injury (AKI). No randomised control trials have compared these regimens. This manuscript describes the protocol and analysis plan for a trial designed to compare the effects of antipseudomonal cephalosporins and antipseudomonal penicillins among acutely ill patients receiving empiric antibiotics. METHODS AND ANALYSIS: The Antibiotic Choice On ReNal outcomes trial is a prospective, single-centre, non-blinded randomised trial being conducted at Vanderbilt University Medical Center. The trial will enrol 2500 acutely ill adults receiving gram-negative coverage for treatment of infection. Eligible patients are randomised 1:1 to receive cefepime or piperacillin-tazobactam on first order entry of a broad-spectrum antibiotic covering gram-negative organisms. The primary outcome is the highest stage of AKI and death occurring between enrolment and 14 days after enrolment. This will be compared between patients randomised to cefepime and randomised to piperacillin-tazobactam using an unadjusted proportional odds regression model. The secondary outcomes are major adverse kidney events through day 14 and number of days alive and free of delirium and coma in 14 days after enrolment. Enrolment began on 10 November 2021 and is expected to be completed in December 2022. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#210591) with a waiver of informed consent. Results will be submitted to a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05094154.

A Quality Improvement Initiative Featuring Peer-Comparison Prescribing Feedback Reduces Emergency Department Opioid Prescribing.

BACKGROUND: Opioid prescribing in the United States nearly tripled from 1999 to 2015, and opioid overdose deaths doubled in the same time frame. Emergency departments (EDs) may play a pivotal role in the opioid epidemic as a source of first-time opioid exposure; however, many prescribers are generally unaware of their prescribing behaviors relative to their peers. METHODS: All 117 ED prescribers at an urban academic medical center were provided with regular feedback on individual rates of opioid prescribing relative to their de-identified peers. To evaluate the effect of this intervention on the departmental rate of opioid prescribing, a statistical process control (SPC) chart was created to identify special cause variation, and an interrupted time series analysis was conducted to evaluate the immediate effect of the intervention and any change in the postintervention trend due to the intervention. RESULTS: The aggregate opioid prescribing rate in the preintervention period was 8.6% (95% confidence interval [CI]: 8.3%-8.9%), while the aggregate postintervention prescribing rate was 5.8% (95% CI: 5.5%-6.1%). The SPC chart revealed special cause variation in both the pre- and postintervention periods, with an overall downtrend of opioid prescribing rates across the evaluation period and flattening of rates in the final four blocks. Interrupted time series analysis demonstrated a significant immediate downward effect of the intervention and a nonsignificant additional decrease in postintervention trend. CONCLUSION: Implementation of peer-comparison opioid prescribing feedback was associated with a significant immediate reduction in the rate of ED discharge opioid prescribing.

Helminth prevalence among adults in rural Kenya: a stool survey for soil-transmitted helminths and schistosomiasis in Nyanza province.

BACKGROUND: Soil-transmitted helminth (STH) prevalence in children is high in rural southwestern Kenya, but adult prevalence data are scarce. A 2010 study of a village in Nyanza province found a pediatric STH prevalence of 44% using a direct stool-smear method. Adult STH prevalence and associated predictors was measured in the same village. METHODS: Adults (≥18 years) presenting at the out-patient department of the small hospital or community outreach events completed a short questionnaire and provided stool samples. Light microscopy for ova and larvae was conducted using a stool concentration technique to improve sensitivity. Multivariable regression models were used to identify predictors of STH prevalence. RESULTS: Among 344 adults, STH prevalence was 15.7% (54/344). Hookworm was most common (13.1%; 45/344), followed by Ascaris lumbricoides (6.1%; 21/344) and Trichuris trichiura (0.6%; 2/344). Twelve participants (3.5%; 12/344) had multiple STHs and three (0.9%; 3/344) had Schistosoma mansoni. Female sex, older age and lower education level were significant STH predictors. CONCLUSIONS: Adult STH prevalence was lower than previous studies of children from the same village. Adults with the identified risk factors had a prevalence of ≥20%, which may warrant periodic, targeted deworming of adults with these risk factors given the low cost and low toxicity of anthelmintic drugs.

Contraction of the ventral abdomen potentiates extracardiac retrograde hemolymph propulsion in the mosquito hemocoel.

BACKGROUND: Hemolymph circulation in mosquitoes is primarily controlled by the contractile action of a dorsal vessel that runs underneath the dorsal midline and is subdivided into a thoracic aorta and an abdominal heart. Wave-like peristaltic contractions of the heart alternate in propelling hemolymph in anterograde and retrograde directions, where it empties into the hemocoel at the terminal ends of the insect. During our analyses of hemolymph propulsion in Anopheles gambiae, we observed periodic ventral abdominal contractions and hypothesized that they promote extracardiac hemolymph circulation in the abdominal hemocoel. METHODOLOGY/PRINCIPAL FINDINGS: We devised methods to simultaneously analyze both heart and abdominal contractions, as well as to measure hemolymph flow in the abdominal hemocoel. Qualitative and quantitative analyses revealed that ventral abdominal contractions occur as series of bursts that propagate in the retrograde direction. Periods of ventral abdominal contraction begin only during periods of anterograde heart contraction and end immediately following a heartbeat directional reversal, suggesting that ventral abdominal contractions function to propel extracardiac hemolymph in the retrograde direction. To test this functional role, fluorescent microspheres were intrathoracically injected and their trajectory tracked throughout the hemocoel. Quantitative measurements of microsphere movement in extracardiac regions of the abdominal cavity showed that during periods of abdominal contractions hemolymph flows in dorsal and retrograde directions at a higher velocity and with greater acceleration than during periods of abdominal rest. Histochemical staining of the abdominal musculature then revealed that ventral abdominal contractions result from the contraction of intrasegmental lateral muscle fibers, intersegmental ventral muscle bands, and the ventral transverse muscles that form the ventral diaphragm. CONCLUSIONS/SIGNIFICANCE: These data show that abdominal contractions potentiate extracardiac retrograde hemolymph propulsion in the abdominal hemocoel during periods of anterograde heart flow.