Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit All?

In a multihospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Proposing the "Continuum of UTI" for a Nuanced Approach to Diagnosis and Management of Urinary Tract Infections.

PURPOSE: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach. MATERIALS AND METHODS: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme. RESULTS: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms. CONCLUSIONS: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.

Your Outpatient has Coronavirus Disease 2019: What Are the Treatment Options in the Current Severe Acute Respiratory Syndrome Coronavirus 2 Variant Climate?

Mutations accumulated by novel Severe Acute Respiratory Syndrome Coronavirus 2 Omicron sublineages contribute to evasion of previously effective monoclonal antibodies for treatment or prevention of Coronavirus Disease 2019 (COVID-19). Other authorized or approved antiviral drugs such as nirmatrelvir/ritonavir, remdesivir, and molnupiravir are, however, predicted to maintain activity against these sublineages and are key tools to reduce severe COVID-19 outcomes in vulnerable populations. A stepwise approach may be taken to target the appropriate antiviral drug to the appropriate patient, beginning with identifying whether a patient is at high risk for hospitalization or other complications of COVID-19. Among higher risk individuals, patient profile (including factors such as age, organ function, and comedications) and antiviral drug access inform suitable antiviral drug selection. When applied in targeted fashion, these therapies serve as a complement to vital ongoing nonpharmaceutical interventions and vaccination strategies that reduce morbidity and maximize protection against COVID-19.

The Disproportionate Impact of Coronavirus Disease 2019 (COVID-19) Pandemic on Healthcare-Associated Infections in Community Hospitals: Need for Expanding the Infectious Disease Workforce.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a considerable impact on US healthcare systems, straining hospital resources, staff, and operations. However, a comprehensive assessment of the impact on healthcare-associated infections (HAIs) across different hospitals with varying level of infectious disease (ID) physician expertise, resources, and infrastructure is lacking. METHODS: This retrospective longitudinal multicenter cohort study included central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), Clostridioides difficile infections (CDIs), and ventilator-associated events (VAEs) from 53 hospitals (academic and community) in Southeastern United States from 1 January 2018 to 31 March 2021. Segmented negative binomial regression generalized estimating equations models estimated changes in monthly incidence rates in the baseline (01/2018-02/2020) compared to the pandemic period (03/2020-03/2021, further divided into three pandemic phases). RESULTS: CLABSIs and VAEs increased by 24% and 34%, respectively, during the pandemic period. VAEs increased in all phases of the pandemic, while CLABSIs increased in later phases of the pandemic. CDI trend increased by 4.2% per month in the pandemic period. On stratifying the analysis by hospital characteristics, the impact of the pandemic on healthcare-associated infections was more significant in smaller sized and community hospitals. CAUTIs did not change significantly during the pandemic across all hospital types. CONCLUSIONS: CLABSIs, VAEs, and CDIs increased significantly during the pandemic, especially in smaller community hospitals, most of which lack ID physician expertise. Future efforts should focus on better understanding challenges faced by community hospitals, strengthening the infection prevention infrastructure, and expanding the ID workforce, particularly to community hospitals.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

Antimicrobial stewardship in solid organ transplant recipients: Current challenges and proposed metrics.

BACKGROUND: Solid organ transplant (SOT) recipients are challenging populations for antimicrobial stewardship interventions due to a variety of reasons, including immunosuppression, consequent risk of opportunistic and donor-derived infections, high rates of infection with multi-drug resistant organisms (MDROs), Clostridioides difficile, and need for prolonged antimicrobial prophylaxis. Despite this, data on stewardship interventions and metrics that address the distinct needs of these patients are limited. METHODS: We performed a narrative review of the current state of antimicrobial stewardship in SOT recipients, existing interventions and metrics in this population, and considerations for implementation of transplant-specific stewardship programs. RESULTS: Antimicrobial stewardship metrics are evolving even in the general patient population. Data on metrics applicable to the SOT population are even more limited. Standard process, outcomes, and balancing metrics may not always apply to the SOT population. A successful stewardship program for SOT recipients requires reviewing existing data, applying general stewardship principles, and understanding the nuances of SOT patients. CONCLUSION: As antimicrobial stewardship interventions are being implemented in SOT recipients; new metrics are needed to assess their impact. In conclusion, SOT patients present a challenging but important opportunity for antimicrobial stewards. ABBREVIATIONS: SOT, antimicrobial stewardship program, MDRO, Clostridioides difficile infection, Centers for Disease Control and Prevention, Infectious Diseases Society of America, prospective audit and feedback, hematopoietic cell transplant, cytomegalovirus, trimethoprim-sulfamethoxazole, surgical site infections, nucleic acid amplification testing, days of therapy, defined daily dose, and length of stay.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

Incidence, risk factors, and outcome of Clostridioides difficile infection following urological surgeries.

PURPOSE: To assess the incidence, risk factors, and clinical outcomes associated with (Clostridioides difficile infection) CDI following urological surgery, which is the leading cause of nosocomial diarrhea and a growing public health burden. METHODS: We queried the National Surgical Quality Improvement Program (NSQIP) to identify patients undergoing urological surgery in 2015-2016. We evaluated the 30-day incidence and factors associated with postoperative CDI and 30-day hospital readmission and length of stay as secondary outcomes. Among the subset of patients undergoing radical cystectomy with urinary diversion (surgery with highest CDI incidence) we used multivariable logistic regression analysis to evaluate independent clinical and demographic factors associated with postoperative CDI. RESULTS: We identified 98,463 patients during the study period. The overall 30-day incidence of CDI was 0.31%, but varied considerably across surgery type. The risk of CDI was greatest following radical cystectomy with urinary diversion (2.72%) compared to all other urologic procedures (0.19%) and was associated with increased risk of hospital readmission (p < 0.0001), re-operation (p < 0.0001), and longer mean length of stay (p < 0.0001) in this cohort. Among patients undergoing radical cystectomy with urinary diversion, multivariable logistic regression revealed that preoperative renal failure (OR: 5.30, 95% CI 1.13-24.9, p = 0.035) and blood loss requiring transfusion (OR: 1.67, 95% CI 1.15-2.44, p = 0.0075) were independently associated with CDI. CONCLUSIONS: In a nationally representative cohort, the incidence of CDI was low but varied substantially across surgery types. CDI was most common following radical cystectomy and associated with potentially modifiable factors such as blood transfusion and significantly longer length of stay.

Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need.

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need.

Two Cases and a Review of Graft-Versus-Host Disease and the Role of Hepatitis C Treatment in Liver Transplant Patients.

Graft-versus-host disease (GvHD) is a rare but fatal complication after solid organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD after orthotopic liver transplantation. Both patients had a history of hepatitis C virus (HCV) infection prior to transplantation. Both cases presented between 1 and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our second case also developed oral and ocular manifestations after liver transplantation, which are more commonly described after stem cell transplantation. Diagnosis in both cases was made by clinical presentation in conjunction with histopathology and flow cytometry. Both patients were treated by increasing immunosuppression with tacrolimus and high-dose steroids. Response to treatment differed based on the degree of pancytopenia. Our case report is distinguished by several factors such as the context of GvHD presentation and the role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to nonspecific presentation that overlaps with other conditions. Furthermore, the relation between HCV treatment and potential initiation of GvHD in solid organ transplant patients is unclear.

The next frontier of healthcare-associated infection (HAI) surveillance metrics: Beyond device-associated infections.

In recent years, it has become increasingly evident that surveillance metrics for invasive device-associated infections (ie, central-line-associated bloodstream infections, ventilator-associated pneumonias, and catheter-associated urinary tract infections) do not capture all harms; they capture only a subset of healthcare-associated infections (HAIs). Although prevention of device-associated infections remains critical, we need to address the full spectrum of potential harms from device use and non-device-associated infections. These include complications associated with additional devices, such as peripheral venous and arterial catheters, non-device-associated infections such as nonventilator hospital-acquired pneumonia, and noninfectious device complications such as trauma, thrombosis, and acute lung injury. As authors of the device-associated infection sections in the SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, we highlight catheter-associated urinary tract infection as an example of the strengths and limitations of the current emphasis on device-associated infection surveillance, suggest performance metrics that present a more comprehensive picture of patient harm, and provide a high-level overview of similar issues with other infection surveillance measures.

Inpatient clinicians' approach to diagnosis of urinary tract infections in older adults using the COM-B model: a qualitative assessment.

Our interviews of inpatient clinicians (physicians, physician assistants) modeled after the Capability, Opportunity, and Motivation Model of Behavior model revealed opportunity and motivation as important drivers for overdiagnosis and overprescribing for asymptomatic bacteriuria in older adults. Understanding these barriers is an important step toward implementing age-friendly stewardship interventions.

Reassessing the management of uncomplicated urinary tract infection: A retrospective analysis using machine learning causal inference.

Background: Uncomplicated urinary tract infection (UTI) is a common indication for outpatient antimicrobial therapy. National guidelines for the management of uncomplicated UTI were published by the Infectious Diseases Society of America in 2011, however it is not fully known the extent to which they align with current practices, patient diversity, and pathogen biology, all of which have evolved significantly in the time since their publication. Objective: We aimed to re-evaluate efficacy and adverse events for first-line antibiotics (nitrofurantoin, and trimethoprim-sulfamethoxazole), versus second-line antibiotics (fluoroquinolones) and versus alternative agents (oral ß-lactams) for uncomplicated UTI in contemporary clinical practice by applying machine learning algorithms to a large claims database formatted into the Observational Medical Outcomes Partnership (OMOP) common data model. Outcomes: Our primary outcome was a composite endpoint for treatment failure, defined as outpatient or inpatient re-visit within 30 days for UTI, pyelonephritis or sepsis. Secondary outcomes were the risk of 4 common antibiotic-associated adverse events: gastrointestinal symptoms, rash, kidney injury and C. difficile infection. Statistical methods: We adjusted for covariate-dependent censoring and treatment indication using a broad set of domain-expert derived features. Sensitivity analyses were conducted using OMOP-learn, an automated feature engineering package for OMOP datasets. Results: Our study included 57,585 episodes of UTI from 49,037 patients. First-line antibiotics were prescribed in 35,018 (61%) episodes, second-line antibiotics were prescribed in 21,140 (37%) episodes and alternative antibiotics were prescribed in 1,427 (2%) episodes. After adjustment, patients receiving first-line therapies had an absolute risk difference of -2.1% [95% CI -2.9% to -1.6%] for having a revisit for UTI within 30 days of diagnosis relative to second-line antibiotics. First-line therapies had an absolute risk difference of -6.6% [95% CI -9.4% to -3.8%] for 30-day revisit compared to alternative ß-lactam antibiotics. Differences in adverse events were clinically similar between first and second line agents, but lower for first-line agents relative to alternative antibiotics (-3.5% [95% CI -5.9% to -1.2%]). Results were similar for models built with OMOPlearn. Conclusion: Our study provides support for the continued use of first-line antibiotics for the management of uncomplicated UTI. Our results also provide proof-of-principle that automated feature extraction methods for OMOP formatted data can emulate manually curated models, thereby promoting reproducibility and generalizability.

Effect of automated identification of antimicrobial stewardship opportunities for suspected urinary tract infections.

Objective: We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention. Design: Retrospective before-and-after study. Setting: Tertiary and quaternary care academic medical center. Patients: Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods. Methods: We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020-12/2020) and post-BPA (04/15/2021-04/30/2022) periods. Results: 774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18-65) in the pre-BPA group compared to 16 hours (IQR 2-34) in the post-BPA group (P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source. Conclusions: Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Five steps to high quality antimicrobial stewardship research.

The escalating threat of antimicrobial resistance (AMR) necessitates impactful, reproducible, and scalable antimicrobial stewardship strategies. This review addresses the critical need to enhance the quality of antimicrobial stewardship intervention research. We propose five considerations for authors planning and evaluating antimicrobial stewardship initiatives. Antimicrobial stewards should consider the following mnemonic ABCDE: (A) plan Ahead using implementation science; (B) Be clear and thoroughly describe the intervention by using the TidIER checklist; (C) Use a Checklist to comprehensively report study components; (D) Select a study Design carefully; and (E) Assess Effectiveness and implementation by selecting meaningful outcomes. Incorporating these recommendations will help strengthen the evidence base of antimicrobial stewardship literature and support optimal implementation of strategies to mitigate AMR.

Evidence gaps among systematic reviews examining the relationship of race, ethnicity, and social determinants of health with adult inpatient quality measures.

Background: The field of healthcare epidemiology is increasingly focused on identifying, characterizing, and addressing social determinants of health (SDOH) to address inequities in healthcare quality. To identify evidence gaps, we examined recent systematic reviews examining the association of race, ethnicity, and SDOH with inpatient quality measures. Methods: We searched Medline via OVID for English language systematic reviews from 2010 to 2022 addressing race, ethnicity, or SDOH domains and inpatient quality measures in adults using specific topic questions. We imported all citations to Covidence (www.covidence.org, Veritas Health Innovation) and removed duplicates. Two blinded reviewers assessed all articles for inclusion in 2 phases: title/abstract, then full-text review. Discrepancies were resolved by a third reviewer. Results: Of 472 systematic reviews identified, 39 were included. Of these, 23 examined all-cause mortality; 6 examined 30-day readmission rates; 4 examined length of stay, 4 examined falls, 2 examined surgical site infections (SSIs) and one review examined risk of venous thromboembolism. The most evaluated SDOH measures were sex (n = 9), income and/or employment status (n = 9), age (n = 6), race and ethnicity (n = 6), and education (n = 5). No systematic reviews assessed medication use errors or healthcare-associated infections. We found very limited assessment of other SDOH measures such as economic stability, neighborhood, and health system access. Conclusion: A limited number of systematic reviews have examined the association of race, ethnicity and SDOH measures with inpatient quality measures, and existing reviews highlight wide variability in reporting. Future systematic evaluations of SDOH measures are needed to better understand the relationships with inpatient quality measures.

Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria.

Importance: Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common. Objectives: To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB. Design, Setting, and Participants: This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023. Main Outcomes and Measures: The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient's risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia. Results: Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia. Conclusions and Relevance: In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.