The Diagnosis and Treatment of Adult Urinary Tract Infections in the Emergency Department.

Emergency medicine has been called the art of "making complicated clinical decisions with limited information." This description is particularly relevant in the case of diagnosis and treatment of urinary tract infections (UTIs). Although common, UTIs are often challenging to diagnose given the presence of non-specific signs and symptoms and over-reliance on laboratory findings. This review provides an interdisciplinary interpretation of the primary literature and practice guidelines, with a focus on diagnostic and antimicrobial stewardship in the emergency department.

The importance of pharmacist engagement in diagnostic stewardship.

Diagnostic stewardship is increasingly recognized as a powerful tool to improve patient safety. Given the close relationship between diagnostic testing and antimicrobial misuse, antimicrobial stewardship (AMS) pharmacists should be key members of the diagnostic team. Pharmacists practicing in AMS already frequently engage with clinicians to improve the diagnostic process and have many skills needed for the implementation of diagnostic stewardship initiatives. As diagnostic stewardship becomes more broadly used, all infectious disease clinicians, including pharmacists, must collaborate to optimize patient care.

Diagnostic stewardship to improve patient outcomes and healthcare-associated infection (HAI) metrics.

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Crossroads of Antimicrobial and Diagnostic Stewardship: Assessing Risks to Develop Clinical Decision Support to Combat Multidrug-Resistant Pseudomonas.

Background: Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)-integrated tool for prediction of MDRP infection. Methods: This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP. Results: The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69-.83] and 0.73 [95% CI, .66-.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57-.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection >3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred. Conclusions: These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.

Developing a diagnosis calculator to estimate the probability of bacterial pneumonia.

Misdiagnosis of bacterial pneumonia increases risk of exposure to inappropriate antibiotics and adverse events. We developed a diagnosis calculator (https://calculator.testingwisely.com) to inform clinical diagnosis of community-acquired bacterial pneumonia using objective indicators, including incidence of disease, risk factors, and sensitivity and specificity of diagnostic tests, that were identified through literature review.

Behavioral Strategies in Diagnostic Stewardship.

Diagnostic stewardship refers to the responsible and judicious use of diagnostic tests to reduce low value care and improve patient outcomes. This article provides an overview of behavioral strategies, their relevance to diagnostic stewardship and highlights behavioral determinants that drive diagnostic testing behavior, drawing on theoretic frameworks. Additionally, we provide concrete examples of evidence-based behavioral strategies for promoting appropriate diagnostic testing while acknowledging associated challenges. Finally, we highlight the significance of evaluating these strategies and provide an overview of evaluation frameworks and methods.

Implementing diagnostic stewardship to improve diagnosis of urinary tract infections across three medical centers: A qualitative assessment.

BACKGROUND: Urine-culture diagnostic stewardship aims to decrease misdiagnosis of urinary tract infections (UTIs); however, these interventions are not widely adopted. We examined UTI diagnosis and management practices to identify barriers to and facilitators of diagnostic stewardship implementation. METHODS: Using a qualitative descriptive design, we conducted semistructured interviews at 3 Veterans' Affairs medical centers. Interviews were conducted between November 2021 and May 2022 via Zoom videoconferencing using an interview guide and visual prototypes of proposed interventions. Interviewees were asked about current practices and thoughts on proposed interventions for urine-culture ordering, processing, and reporting. We used a rapid analysis matrix approach to summarize key interview findings and compare practices and perceptions across sites. RESULTS: We interviewed 31 stakeholders and end users. All sites had an antimicrobial stewardship program but limited initiatives targeting appropriate diagnosis and management of UTIs. The majority of those interviewed identified the importance of diagnostic stewardship. Perceptions of specific interventions ranged widely by site. For urine-culture ordering, all 3 sites agreed that documentation of symptomology would improve culturing practices but did not want it to interrupt workflow. Representatives at 2 sites expressed interest in conditional urine-culture processing and 1 was opposed. All sites had similar mechanisms to report culture results but varied in perceptions of the proposed interventions. Feedback from end users was used to develop a general diagnostic stewardship implementation checklist. CONCLUSION: Interviewees thought diagnostic stewardship was important. Qualitative assessment involving key stakeholders in the UTI diagnostic process improved understanding of site-specific beliefs and practices to better implement interventions for urine-culture ordering, processing, and reporting.

Diagnostic stewardship: what impacts antibiotics use?

PURPOSE OF REVIEW: The aim of this study was to review recently published diagnostic stewardship studies of common clinical infectious syndromes and the impact on antibiotic prescribing. RECENT FINDINGS: Diagnostic stewardship can be implemented within healthcare systems and tailored to infectious syndromes, including urinary tract, gastrointestinal, respiratory and bloodstream infections. In urinary syndromes, diagnostic stewardship can decrease unnecessary urine culturing and associated antibiotic prescribing. Diagnostic stewardship of Clostridium difficile testing can decrease antibiotics and test ordering with a reduction in healthcare-associated C. difficile infections. Respiratory syndrome multiplex arrays can decrease time to results and increase detection of clinically relevant pathogens but may not decrease antibiotics use, or worse, could increase over-prescribing if diagnostic stewardship of ordering practices is not exercised. Lastly, blood culturing practices can be improved by clinical decision support to safely decrease collection and broad-spectrum antibiotic use. SUMMARY: Diagnostic stewardship decreases unnecessary antibiotic use in a way that is different from and complementary to antibiotic stewardship. Further studies are needed to quantify the full impact on antibiotic use and resistance. Future considerations should be to institutionalize diagnostic stewardship in patient care activities to leverage integration into systems-based interventions.

From bottle to bedside: Implementation considerations and antimicrobial stewardship considerations for bloodstream infection rapid diagnostic testing.

Antimicrobial stewardship (AMS) programs have been quick to adopt novel molecular rapid diagnostic technologies (mRDTs) for bloodstream infections (BSIs) to improve antimicrobial management. As such, most of the literature demonstrating the clinical and economic benefits of mRDTs for BSI is in the presence of active AMS intervention. Leveraging mRDTs to improve antimicrobial therapy for BSI is increasingly integral to AMS program activities. This narrative review discusses available and future mRDTs, the relationship between the clinical microbiology laboratory and AMS programs, and practical considerations for optimizing the use of these tools within a health system. Antimicrobial stewardship programs must work closely with their clinical microbiology laboratories to ensure that mRDTs are used to their fullest benefit while remaining cognizant of their limitations. As more mRDT instruments and panels become available and AMS programs continue to expand, future efforts must consider the expansion beyond traditional settings of large academic medical centers and how combinations of tools can further improve patient care.

Clinical, contextual and hospital-level factors associated with escalation and de-escalation of empiric Gram-negative antibiotics among US inpatients.

Background: Empiric Gram-negative antibiotics are frequently changed in response to new information. To inform antibiotic stewardship, we sought to identify predictors of antibiotic changes using information knowable before microbiological test results. Methods: We performed a retrospective cohort study. Survival-time models were used to evaluate clinical factors associated with antibiotic escalation and de-escalation (defined as an increase or decrease, respectively, in the spectrum or number of Gram-negative antibiotics within 5 days of initiation). Spectrum was categorized as narrow, broad, extended or protected. Tjur's D statistic was used to estimate the discriminatory power of groups of variables. Results: In 2019, 2 751 969 patients received empiric Gram-negative antibiotics at 920 study hospitals. Antibiotic escalation occurred in 6.5%, and 49.2% underwent de-escalation; 8.8% were changed to an equivalent regimen. Escalation was more likely when empiric antibiotics were narrow-spectrum (HR 19.0 relative to protected; 95% CI: 17.9-20.1), broad-spectrum (HR 10.3; 95% CI: 9.78-10.9) or extended-spectrum (HR 3.49; 95% CI: 3.30-3.69). Patients with sepsis present on admission (HR 1.94; 95% CI: 1.91-1.96) and urinary tract infection present on admission (HR 1.36; 95% CI: 1.35-1.38) were more likely to undergo antibiotic escalation than patients without these syndromes. De-escalation was more likely with combination therapy (HR 2.62 per additional agent; 95% CI: 2.61-2.63) or narrow-spectrum empiric antibiotics (HR 1.67 relative to protected; 95% CI: 1.65-1.69). Choice of empiric regimen accounted for 51% and 74% of the explained variation in antibiotic escalation and de-escalation, respectively. Conclusions: Empiric Gram-negative antibiotics are frequently de-escalated early in hospitalization, whereas escalation is infrequent. Changes are primarily driven by choice of empiric therapy and presence of infectious syndromes.

Impact of a real-time diagnostic and antimicrobial stewardship workflow on time to appropriate therapy for infections caused by multidrug-resistant Gram-negative organisms.

INTRODUCTION: Multidrug-resistant (MDR) Gram-negative organisms cause life-threatening infections, and the incidence is rising globally. Timely therapy for these infections has a direct impact on patient survival. This study aimed to determine the impact of a multidisciplinary diagnostic and antimicrobial stewardship (AMS) workflow on time to appropriate therapy (TAP) for these infections using novel beta-lactam/beta-lactamase inhibitors. METHODS: This was a retrospective quasi-experimental study of adult patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas (MDR PsA) infections at a 1500 bed university hospital. Included patients who received ≥ 72 hours of ceftazidime-avibactam (CZA) or ceftolozane-tazobactam (C/T) from December 2017 to December 2019. During the pre-intervention period (December 2017 to December 2018), additional susceptibilities (including CZA and C/T) were performed only upon providers' request. In 2019, reflex algorithms were implemented for faster identification and testing of all CRE/MDR PsA isolates. Results were communicated in real-time to the AMS team to tailor therapy. RESULTS: A total of 99 patients were included, with no between-group differences at baseline. The median age was 60 years and 56 (56.7%) were in intensive care at the time of culture collection. Identified organisms included 71 (71.7%) MDR PsA and 26 CRE, of which 18 were carbapenemase producers (Klebsiella-producing carbapenemase = 12, New Delhi metallo-ß-lactamase = 4, Verona integron-encoded metallo-ß-lactamase = 2). The most common infections were pneumonia (49.5%) and bacteraemia (30.3%). A decrease was found in median TAP (103 [IQR 76.0-156.0] vs. 75 [IQR 56-100] hours; P < 0.001). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (123 vs. 93 hours; P < 0.001). CONCLUSION: This study identified improvement in TAP in MDR PsA and CRE infections with implementation of a reflex microbiology workflow and multidisciplinary antimicrobial stewardship initiatives.

Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Evaluating the Follow-up of Post-discharge Positive Sterile Site Cultures and the Impact on Infection-Related Complications.

INTRODUCTION: Numerous patients have cultures pending at discharge which, if not addressed, may delay diagnosis and initiation of appropriate antimicrobials. The purpose of the study is to evaluate the appropriateness of discharge antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. METHODS: This was a cross-sectional cohort study of patients admitted from July 1 to December 31, 2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥ 48 h and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial changes based on finalized cultures. Secondary objectives included prevalence and timeliness of result documentation and rates of 30-day readmission, among intervention warranted versus not warranted. Chi-squared or Fisher's exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day readmission stratified by infectious disease (ID) involvement due to the potential for effect modification. RESULTS: A total of 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Change in discharge antimicrobial was warranted in 36.5% of patients (n = 76). Result documentation was overall low (35.5%). Time to documentation was significantly shorter in patients warranting antimicrobial intervention (4 days vs. 9 days, P = 0.039), although rates of hospital readmission were higher in this group (32.9% vs. 22.7%, P = 0.109). Finally, in patients not being followed by ID, documentation of finalized results was associated with decreased odds of 30-day readmission (aOR 0.19; 95% CI 0.07-0.53). CONCLUSIONS: A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of finalized culture results may decrease the risk of 30-day hospital readmission, particularly in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and action on pending cultures to positively impact patient outcomes.

Leveraging diagnostic stewardship within antimicrobial stewardship programmes.

Novel diagnostic stewardship in infectious disease consists of interventions that modify ordering, processing, and reporting of diagnostic tests to provide the right test for the right patient, prompting the right action. The interventions work upstream and synergistically with traditional antimicrobial stewardship efforts. As diagnostic stewardship continues to gain public attention, it is critical that antimicrobial stewardship programmes not only learn how to effectively leverage diagnostic testing to improve antimicrobial use but also ensure that they are stakeholders and leaders in developing new diagnostic stewardship interventions within their institutions. This review will discuss the need for diagnostic and antimicrobial stewardship, the interplay of diagnostic and antimicrobial stewardship, evidence of benefit to antimicrobial stewardship programmes, and considerations for successfully engaging in diagnostic stewardship interventions. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

Understanding healthcare provider preferences for ordering respiratory cultures to diagnose ventilator associated pneumonia: A discrete choice experiment.

Objective: Ventilator-associated pneumonia (VAP) can be overdiagnosed on the basis of positive respiratory cultures in the absence of clinical findings of pneumonia. We determined the perceived diagnostic importance of 6 clinical attributes in ordering a respiratory culture to identify opportunities for diagnostic stewardship. Design: A discrete choice experiment presented participants with a vignette consisting of the same "stem" plus variations in 6 clinical attributes associated with VAP: chest imaging, oxygenation, sputum, temperature, white blood cell count, and blood pressure. Each attribute had 3-4 levels, resulting in 32 total scenarios. Participants indicated whether they would order a respiratory culture, and if yes, whether they preferred the bronchoalveolar lavage or endotracheal aspirate sample-collection method. We calculated diagnostic utility of attribute levels and relative importance of each attribute. Setting and participants: The survey was administered electronically to critical-care clinicians via a Qualtrics survey at a tertiary-care academic center in the United States. Results: In total, 59 respondents completed the survey. New radiograph opacity (utility, 1.15; 95% confidence interval [CI], 0.99-1.3), hypotension (utility, 0.88; 95% CI, 0.74-1.03), fever (utility, 0.76; 95% CI, 0.62-0.91) and copious sputum (utility, 0.75; 95% CI, 0.60-0.90) had the greatest perceived diagnostic value that favored ordering a respiratory culture. Radiograph changes (23%) and temperature (20%) had the highest relative importance. New opacity (utility, 0.35; 95% CI, 0.17-0.52) and persistent opacity on radiograph (utility, 0.32; 95% CI, 0.05-0.59) had the greatest value favoring bronchoalveolar lavage over endotracheal aspirate. Conclusion: Perceived high diagnostic value of fever and hypotension suggest that sepsis vigilance may drive respiratory culturing and play a role in VAP overdiagnosis.

Evaluating the incidence of bacteriuria in female patients before and after implementation of external urinary collection devices.

External urinary collection devices (ECDs) are increasingly used in female patients, however, their impact on bacteriuria and antimicrobial use is unclear. Comparing the periods before and after the implementation of an ECD use policy, we found an overall decrease in bacteriuria but no significant decrease in trend of monthly rates. Antimicrobial use for genitourinary indications did not change.

Real-world Antimicrobial Stewardship Experience in a Large Academic Medical Center: Using Statistical and Machine Learning Approaches to Identify Intervention "Hotspots" in an Antibiotic Audit and Feedback Program.

Background: Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient. Methods: We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center's PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data. Results: Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63-3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A "workflow simplified" regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning-identified predictors, reduced reviews by one-third while achieving 81% sensitivity. Conclusions: Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.