Evaluation of a Comprehensive Algorithm for PICU Patients With New Fever or Instability: Association of Clinical Decision Support With Testing Practices.

OBJECTIVES: Previously, we implemented a comprehensive decision support tool, a "New Fever Algorithm," to support the evaluation of PICU patients with new fever or instability. This tool was associated with a decline in culture rates without safety concerns. We assessed the impact of the algorithm on testing practices by identifying the proportion of cultures pre- vs. post-implementation that were discordant with algorithm guidance and may have been avoidable. DESIGN: Retrospective evaluation 12 months pre- vs. post-quality improvement intervention. SETTING: Single-center academic PICU and pediatric cardiac ICU. SUBJECTS: All admitted patients. INTERVENTIONS: Implementing the "New Fever Algorithm" in July 2020. MEASUREMENTS AND MAIN RESULTS: Patient medical records were reviewed to categorize indications for all blood, respiratory, and urine cultures. Among cultures obtained for new fever or new clinical instability, we assessed specific testing patterns that were discordant from the algorithm's guidance such as blood cultures obtained without documented concern for sepsis without initiation of antibiotics, respiratory cultures without respiratory symptoms, urine cultures without a urinalysis or pyuria, and pan-cultures (concurrent blood, respiratory, and urine cultures). Among 2827 cultures, 1950 (69%) were obtained for new fever or instability. The proportion of peripheral blood cultures obtained without clinical concern for sepsis declined from 18.6% to 10.4% (p < 0.0007). Respiratory cultures without respiratory symptoms declined from 41.5% to 27.4% (p = 0.01). Urine cultures without a urinalysis did not decline (from 27.6% to 25.1%). Urine cultures without pyuria declined from 83.0% to 73.7% (p = 0.04). Pan-cultures declined from 22.4% to 10.6% (p < 0.0001). Overall, algorithm-discordant testing declined from 39% to 30% (p < 0.0001). CONCLUSIONS: The majority of cultures obtained were for new fever or instability and introduction of the "New Fever Algorithm" was associated with reductions in algorithm-discordant testing practices and pan-cultures. There remain opportunities for improvement and additional strategies are warranted to optimize testing practices for in this complex patient population.

Train the Trainer in Bleeding Control: A Two-Year Pilot Study in Low-Income and Middle-Income Countries.

INTRODUCTION: Traumatic hemorrhage represents a major cause of mortality in low-income and middle-income countries (LMICs). Thus, LMICs can benefit from improvements to prehospital hemorrhage management. One strategy is implementation of a bleeding control course using the "train the trainer" model (TTT) to increase course availability. The Stop the Bleed (STB) campaign provides laypeople with basic knowledge and skills of hemorrhage control. While the feasibility and success of the STB course have been demonstrated in the United States, course dissemination in LMICs has been slower and its feasibility using the TTT model has not been established. MATERIALS AND METHODS: From December 2017 to January 2019, instructors from the International Surgical Health Initiative conducted seven surgical humanitarian trips and taught 10 index 1-h STB training sessions across six LMICs. LMIC instructors were encouraged to continue providing STB courses following departure of the visiting instructors. Course data were collected from sign-in sheets and analyzed using Microsoft Excel. RESULTS: Ten index courses conducted by United States-trained STB experts trained 35 LMIC instructors over 2 y. Six of 35 offered 12 additional courses, certifying 323 new trainees, an 823% increase from the initial cohort. Overall, implementation of the TTT model yielded 22 STB courses in six LMICs, producing 358 new trainees. CONCLUSIONS: This pilot study shows the STB TTT model was feasible and effective in expanding bleeding control trainer capacity in four of six LMICs. Use of the TTT model in LMICs may represent a means to increase STB course availability and is one strategy to improve prehospital hemorrhage control in LMICs.

The Impact of Global Collaboration on the Academic Focus of the West African College of Surgeons: Are Worldwide Efforts Aligning with Local Priorities?

BACKGROUND: Global collaboration has the potential to induce a shift in research focus away from the priorities of those in low- and low-middle-income countries (LICs and LMICs). This study quantified international collaboration among surgery publications by Fellows of the West African College of Surgeons (WACS) and investigated if collaboration with upper-middle-income and high-income countries (UMICs and HICs) decreases the homophily of research focus. METHODS: Publications by WACS surgery Fellows from 1960 to 2019 were characterized as local WACS publications, collaborative publications without UMIC/HIC participation, or collaborative publications with UMIC/HIC participation. Research topics were determined for each publication, and topic percentages were compared between collaboration groups. RESULTS: We analyzed 5065 publications. Most (3690 publications, 73%) were local WACS publications, while 742 (15%) were collaborative publications with UMIC/HIC participation and 633 (12%) were collaborative publications without UMIC/HIC participation. UMIC/HIC collaborations contributed to 49% of the increase (378 out of 766 publications) from 2000 to 2019. Topic homophily was significantly lower between local WACS publications and collaborations with UMIC/HIC participation (differed in nine research topics) than it was between local WACS publications and collaborations without UMIC/HIC participation (differed in two research topics). CONCLUSIONS: Publications without international collaboration comprise most WACS research, but the rate of UMIC/HIC collaborations is rapidly increasing. We found that UMIC/HIC collaborations decreased the homophily of topic focus in WACS publications, indicating that global collaborations need to have greater emphasis on the priorities of those in LICs and LMICs.

Staphylococcus lugdunensis Endocarditis Presenting with Brain Abscesses and Temporal Vision Deficits.

Staphylococcus lugdunensis is a coagulase-negative staphylococcal bacterium (CoNS) that colonizes the skin. While infectious endocarditis (IE) caused by S. lugdunensis is rare, it is noteworthy because it has been associated with an aggressive clinical course. In this report, we present a case of culture-negative IE complicated by brain abscesses, vision deficits, and progressive heart failure that ultimately required mitral valve replacement. The causative agent was eventually identified as S. lugdunensis through molecular testing of valvular tissue.

Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections.

The pathogenic bacterium Staphylococcus aureus is the most common pathogen isolated in skin-and-soft-tissue infections (SSTIs) in the United States. Most S. aureus SSTIs are caused by the epidemic clone USA300 in the USA. These infections can be serious; in 2019, SSTIs with S. aureus were associated with an all-cause, age-standardized mortality rate of 0.5 globally. Clinical presentations of S. aureus SSTIs vary from superficial infections with local symptoms to monomicrobial necrotizing fasciitis, which can cause systemic manifestations and may lead to serious complications or death. In order to cause skin infections, S. aureus employs a host of virulence factors including cytolytic proteins, superantigenic factors, cell wall-anchored proteins, and molecules used for immune evasion. The immune response to S. aureus SSTIs involves initial responders such as keratinocytes and neutrophils, which are supported by dendritic cells and T-lymphocytes later during infection. Treatment for S. aureus SSTIs is usually oral therapy, with parenteral therapy reserved for severe presentations; it ranges from cephalosporins and penicillin agents such as oxacillin, which is generally used for methicillin-sensitive S. aureus (MSSA), to vancomycin for methicillin-resistant S. aureus (MRSA). Treatment challenges include adverse effects, risk for Clostridioides difficile infection, and potential for antibiotic resistance.

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues.

Bacterial virulence genes are often regulated at the transcriptional level by multiple factors that respond to different environmental signals. Some factors act directly on virulence genes; others control pathogenesis by adjusting the expression of downstream regulators or the accumulation of signals that affect regulator activity. While regulation has been studied extensively during in vitro growth, relatively little is known about how gene expression is adjusted during infection. Such information is important when a particular gene product is a candidate for therapeutic intervention. Transcriptional approaches like quantitative, real-time RT-PCR and RNA-Seq are powerful ways to examine gene expression on a global level but suffer from many technical challenges including low abundance of bacterial RNA compared to host RNA, and sample degradation by RNases. Evaluating regulation using fluorescent reporters is relatively easy and can be multiplexed with fluorescent proteins with unique spectral properties. The method allows for single-cell, spatiotemporal analysis of gene expression in tissues that exhibit complex three-dimensional architecture and physiochemical gradients that affect bacterial regulatory networks. Such information is lost when data are averaged over the bulk population. Herein, we describe a method for quantifying gene expression in bacterial pathogens in situ. The method is based on simple tissue processing and direct observation of fluorescence from reporter proteins. We demonstrate the utility of this system by examining the expression of Staphylococcus aureus thermonuclease (nuc), whose gene product is required for immune evasion and full virulence ex vivo and in vivo. We show that nuc-gfp is strongly expressed in renal abscesses and reveal heterogeneous gene expression due in part to apparent spatial regulation of nuc promoter activity in abscesses fully engaged with the immune response. The method can be applied to any bacterium with a manipulatable genetic system and any infection model, providing valuable information for preclinical studies and drug development.