Effectiveness and Safety of an Emergency Department Code Sepsis Protocol: A Pragmatic Clinical Trial.

RATIONALE: Sepsis care delivery - including initiation of prompt, appropriate antimicrobials - remains suboptimal. OBJECTIVE: Determine direct and off-target effects of emergency department (ED) sepsis care reorganization. METHODS: This pragmatic pilot trial enrolled adult patients presenting November 2019 to February 2021 to an ED in Utah before and after implementation of a multimodal, team-based "Code Sepsis" protocol. Patients presenting to two other EDs where usual care was continued served as contemporaneous controls. The primary outcome was door-to-antimicrobial time among patients meeting Sepsis-3 criteria before ED departure. Secondary and safety outcomes included all-cause 30-day mortality, antimicrobial utilization and overtreatment, and antimicrobial-associated adverse events. Multivariable regression analyses employed difference-in-differences methods to account for trends in outcomes unrelated to the studied intervention. RESULTS: Code Sepsis protocol activation (N=307) exhibited 8.5% sensitivity and 66% positive predictive value for patients meeting sepsis criteria before ED departure. Among 10,151 patients meeting sepsis criteria during the study, adjusted difference-in-differences analysis demonstrated a 13-minute (95% CI 7-19-minute) decrease in door-to-antimicrobial time associated with Code Sepsis implementation (p<0.001). Mortality and clinical safety outcomes were unchanged, but Code Sepsis implementation was associated with increased false-positive presumptive infection diagnosis among patients meeting sepsis criteria in the ED and increased antimicrobial utilization. CONCLUSIONS: Implementation of a team-based protocol for rapid sepsis evaluation and treatment during the COVID-19 pandemic's first year was associated with decreased ED door-to-antimicrobial time but also increased antimicrobial utilization. Measurement of both patient-centered and off-target effects of sepsis care improvement interventions is essential to comprehensive assessment of their value. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04148989) This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Outcomes of patients with bacteriuria/pyuria of clinically undetermined significance (BPCUS) treated with antibiotics in 23 community hospital emergency departments.

The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.

Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

A Novel Program to Provide Drug Recovery Assistance and Outpatient Parenteral Antibiotic Therapy in People Who Inject Drugs.

BACKGROUND: Safe hospital discharge on parenteral antibiotic therapy is challenging for people who inject drugs (PWID) admitted with serious bacterial infections (SBI). We describe a Comprehensive Care of Drug Addiction and Infection (CCDAI) program involving a partnership between Intermountain Healthcare hospitals and a detoxification facility (DF) to provide simultaneous drug recovery assistance and parenteral antibiotic therapy (DRA-OPAT). METHODS: The CCDAI program was evaluated using a pre-/poststudy design. We compared outcomes in PWID hospitalized with SBI during a 1-year postimplementation period (2018) with similar patients from a historical control period (2017), identified by propensity modeling and manual review. RESULTS: Eighty-seven patients were candidates for the CCDAI program in the implementation period. Thirty-five participants (40.2%) enrolled in DRA-OPAT and discharged to the DF; 16 (45.7%) completed the full outpatient parenteral antibiotic therapy (OPAT) duration. Fifty-one patients with similar characteristics were identified as a preimplementation control group. Median length of stay (LOS) was reduced from 22.9 days (interquartile interval [IQI], 9.8-42.7) to 10.6 days (IQI, 6-17.4) after program implementation (P < .0001). Total median cost decreased from $39 220.90 (IQI, $23 300.71-$82 506.66) preimplementation to $27 592.39 (IQI, $18 509.45-$48 369.11) postimplementation (P < .0001). Ninety-day readmission rates were similar (23.5% vs 24.1%; P = .8). At 1-year follow-up, all-cause mortality was 7.1% in the preimplementation group versus 1.2% postimplementation (P = .06). CONCLUSIONS: Partnerships between hospitals and community resources hold promise for providing resource-efficient OPAT and drug recovery assistance. We observed significant reductions in LOS and cost without increases in readmission rates; 1-year mortality may have been improved. Further study is needed to optimize benefits of the program.

Clostridium botulinum - like organism bacteremia in a user of black tar heroin.

Wound botulism due to introduction of the anaerobic bacteria, Clostridium botulinum, into otherwise sterile, relatively anaerobic tissue is a known complication of black tar heroin use. The treatment of wound botulism requires prompt initiation of antitoxin as well as antimicrobial therapy. We report the case of a patient with polymicrobial bacteremia that included a Clostridium botulinum-like organism who underwent successful treatment of their anaerobic infection with antibiotics and surgical debridement.

Interventions to optimize antimicrobial stewardship.

Developing and improving an antimicrobial stewardship program successfully requires evaluation of numerous factors. As technology progresses and our understanding of antimicrobial resistance grows, careful consideration should be taken to ensure that a program meets the needs of the institution and is achievable given the available resources. In this review, we explore fundamental initiatives and strategies for both new and established antimicrobial stewardship programs, including the specific areas to target and key elements required for sustainable implementation.

Genomic relationships among sixteen species of Avena based on (ACT)6 trinucleotide repeat FISH.

Knowledge of the locations of repeat elements could be very important in the assembly of genome sequences and their assignment to physical chromosomes. Genomic and species relationships among 16 species were investigated using fluorescence in situ hybridization (FISH) with the Am1 and (ACT)6 probes. The Am1 oligonucleotide probe was particularly enriched in the C genomes, whereas the (ACT)6 trinucleotide repeat probe showed a diverse distribution of hybridization patterns in the A, AB, C, AC, and ACD genomes but might not be present in the B and D genomes. The hybridization pattern of Avena sativa was very similar to that of A. insularis, indicating that this species most likely originated from A. insularis as a tetraploid ancestor. Although the two FISH probes failed to identify relationships of more species, this proof-of-concept approach opens the way to the use of FISH probes in assigning other signature elements from genomic sequence to physical chromosomes.

Genetic and physical mapping of Lrk10-like receptor kinase sequences in hexaploid oat (Avena sativa L.).

Oat receptor-like kinase gene sequences, homologous to the Lrk10 gene from wheat (Triticum aestivum L.), were mapped in oat (Avena sativa L.). PCR primers designed from the wheat Lrk10 were used to produce ALrk10 from oat. Two DNA sequences, ALrk1A1 and ALrk4A5, were produced from primers designed from coding and noncoding regions of ALrk10. Their use as RFLP probes indicated that the kinase genes mapped to four loci on different hexaploid oat 'Kanota' x 'Ogle' linkage groups (4_12, 5, 6, and 13) and to a fifth locus unlinked to other markers. Three of these linkage groups contain a region homologous to the short arm of chromosome I of wheat and the fourth contains a region homologous to chromosome 3 of wheat. Analysis with several nullisomics of oat indicated that two of the map locations are on satellite chromosomes. RFLP mapping in a 'Dumont' x 'OT328' population indicated that one map location is closely linked to Pg9, a resistance gene to oat stem rust (Puccinia graminis subsp. avenae). Comparative mapping indicates this to be the region of a presumed cluster of crown rust (Puccinia coronata subsp. avenae) and stem rust resistance genes (Pg3, Pg9, Pc44, Pc46, Pc50, Pc68, Pc95, and PcX). The map position of several RGAs located on KO6 and KO3_38 with respect to Lrk10 and storage protein genes are also reported.