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The advent of rapid molecular microbiology testing has revolutionized infectious disease diagnostics and is now impacting pneumonia diagnosis and management. Molecular platforms offer highly multiplexed assays for diverse viral and bacterial detection, alongside antimicrobial resistance markers, providing the potential to significantly shape patient care. Despite the superiority in sensitivity and speed, debates continue regarding the clinical role of multiplex molecular testing, notably in comparison to standard methods and distinguishing colonization from infection. Recent guidelines endorse molecular pneumonia panels for enhanced sensitivity and rapidity, but implementation requires addressing methodological differences and ensuring clinical relevance. Diagnostic stewardship should be leveraged to optimize pneumonia testing, emphasizing pre- and post-analytical strategies. Collaboration between clinical microbiologists and bedside providers is essential in developing implementation strategies to maximize the clinical utility of multiplex molecular diagnostics in pneumonia. This narrative review explores these multifaceted issues, examining the current evidence on the clinical performance of multiplex molecular assays in pneumonia, and reflects on lessons learned from previous microbiological advances. Additionally, given the complexity of pneumonia and the sensitivity of molecular diagnostics, diagnostic stewardship is discussed within the context of current literature, including implementation strategies that consider pre-analytical and post-analytical modifications to optimize the clinical utility of advanced technologies like multiplex PCR. [ABSTRACT FROM AUTHOR]

Bacteremia is associated with significant morbidity and mortality. Timely, appropriate therapy may improve clinical outcomes, and therefore, determining which patients benefit from more comprehensive diagnostic strategies (i.e., direct specimen testing) could be of value. We performed an assessment of procalcitonin (PCT) and clinical characteristics in the discrimination of bacteremic hospitalizations. We analyzed 71,105 encounters and 14,846 visits of patients with bacteremia alongside 56,259 without an admission. The area under the receiver—operating characteristic (AUROC) curve for the prediction of bacteremia via procalcitonin was 0.782 (95% CI 0.779–0.787). The prediction modeling of clinical factors with or without PCT resulted in a similar performance to PCT alone. However, the clinically predicted risk of bacteremia stratified by PCT thresholds allowed the targeting of high-incidence bacteremia groups (e.g., ≥50% positivity). The combined use of PCT and clinical characteristics could be useful in diagnostic stewardship by targeting further advanced diagnostic testing in patients with a high predicted probability of bacteremia. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance (AMR) surveillance is critical in informing strategies for infection control in slowing the spread of resistant organisms and for antimicrobial stewardship in the care of patients. However, significant challenges exist in timely and comprehensive AMR surveillance. Methods Using BioFire Pneumonia and Blood Culture 2 Panels data from BioFire Syndromic Trends (Trend), a cloud-based population surveillance network, we described the detection rate of AMR among a US cohort. Data were included from 2019 to 2021 for Gram-positive and -negative organisms and their related AMR genomic-resistant determinants as well as for detections of Candida auris. Regional and between panel AMR detection rate differences were compared. In addition, AMR codetections and detection rate per organism were evaluated for Gram-negative organisms. Results A total of 26 912 tests were performed, primarily in the Midwest. Overall, AMR detection rate was highest in the South and more common for respiratory specimens than blood. methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus detection rates were 34.9% and 15.9%, respectively, whereas AMR for Gram-negative organisms was lower with 7.0% CTX-M and 2.9% carbapenemases. In addition, 10 mcr-1 and 4 C auris detections were observed. For Gram-negative organisms, Klebsiella pneumoniae and Escherichia coli were most likely to be detected with an AMR gene, and of Gram-negative organisms, K pneumoniae was most often associated with 2 or more AMR genes. Conclusions Our study provides important in-depth evaluation of the epidemiology of AMR among respiratory and blood specimens for Gram-positive and -negative organism in the United States. The Trend surveillance network allows for near real-time surveillance of AMR. [ABSTRACT FROM AUTHOR]

Background Evidence supports streamlined approaches for inpatients with community-acquired pneumonia (CAP) including early transition to oral antibiotics and shorter therapy. Uptake of these approaches is variable, and the best approaches to local implementation of infection-specific guidelines are unknown. Our objective was to evaluate the impact of a clinical decision support (CDS) tool linked with a clinical pathway on CAP care. Methods This is a retrospective, observational pre–post intervention study of inpatients with pneumonia admitted to a single academic medical center. Interventions were introduced in 3 sequential 6-month phases; Phase 1: education alone; Phase 2: education and a CDS-driven CAP pathway coupled with active antimicrobial stewardship and provider feedback; and Phase 3: education and a CDS-driven CAP pathway without active stewardship. The 12 months preceding the intervention were used as a baseline. Primary outcomes were length of intravenous antibiotic therapy and total length of antibiotic therapy. Clinical, process, and cost outcomes were also measured. Results The study included 1021 visits. Phase 2 was associated with significantly lower length of intravenous and total antibiotic therapy, higher procalcitonin lab utilization, and a 20% cost reduction compared with baseline. Phase 3 was associated with significantly lower length of intravenous antibiotic therapy and higher procalcitonin lab utilization compared with baseline. Conclusions A CDS-driven CAP pathway supplemented by active antimicrobial stewardship review led to the most robust improvements in antibiotic use and decreased costs with similar clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose. The implementation and optimization of molecular rapid diagnostic tests (mRDTs) as an antimicrobial stewardship intervention for patients with bloodstream infections (BSIs) are reviewed. Summary. All U.S. acute care hospitals accredited by the Joint Commission are required to implement an antimicrobial stewardship program (ASP). Of the many interventions available to ASPs, mRDTs have demonstrated consistent, meaningful results on antimicrobial optimization and patient outcomes. Even among infectious diseases and antimicrobial stewardship--trained pharmacists, significant knowledge and familiarity gaps exist regarding available mRDTs and how best to implement and optimize them. Given the paucity of infectious diseases and/or antimicrobial stewardship--trained pharmacists, the mandates for establishing ASPs will require non-infectious diseases/antimicrobial stewardship--trained pharmacists to implement stewardship interventions, which may include mRDTs, within their institution. Optimization of mRDTs requires adequate diagnostic stewardship, specifically evaluating how mRDT implementation may decrease costs and assist in meeting antimicrobial stewardship regulatory requirements. Knowledge of how these technologies will augment existing microbiology and antimicrobial stewardship workflow is essential. Finally, selecting the right mRDT necessitates familiarity with the instrument's capabilities and with the institutional antibiogram. Conclusion. mRDTs have demonstrated the ability to be one of the most powerful antimicrobial stewardship interventions. Pharmacists required to implement an ASP in their institution should consider mRDTs as standard of care for patients with BSIs. [ABSTRACT FROM AUTHOR]

The article discusses that the Viral infections are common among patients admitted to hospitals with acute respiratory failure and are reported in at least 30–40% of cases. It mentions that randomized trials for multiplex respiratory RDT in patients presenting to the hospital suggest that testing closest to the time of presentation is most impactful on management decisions and outcomes; and the synergistic relationship between active ASP interventions and RDT.

Study Objective: Current guidelines recommend higher daptomycin doses than the daptomycin label dose of 6 mg/kg for methicillin‐resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from in vitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia. Design: Retrospective national cohort study. Setting: Veterans Affairs medical centers. Patients: A total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24 hours of initial culture collection and then switched to daptomycin therapy within 7 days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7 mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6 mg/kg). Measurements and Main Results: Clinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score–matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30‐day mortality disease risk score. Propensity score–matched 30‐day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10–0.94). No significant differences were observed in inpatient mortality, length of stay, 30‐day readmission, or 30‐day S. aureus reinfection between groups. CART analysis resulted in doses of 7 mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30‐day mortality (p<0.001). Conclusion: To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7 mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.Data Sources: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.Study Selection: Articles not in English, pediatric studies, and case reports were excluded.Data Extraction: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.Data Synthesis: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).Conclusions: The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed. [ABSTRACT FROM AUTHOR]

Background. Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs. Methods. We searched PubMed, CINAHL,Web of Science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes between mRDT and conventional microbiology methods. Results. Thirty-one studies were included with 5920 patients. The mortality risk was significantly lower with mRDT than with conventional microbiology methods (odds ratio [OR], 0.66; 95% confidence interval [CI], .54-.80), yielding a number needed to treat of 20. The mortality risk was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR, 0.64; 95% CI, .51-.79), and non-ASP studies failed to demonstrate a significant decrease in mortality risk (0.72; .46-1.12). Significant decreases in mortality risk were observed with both gram-positive (OR, 0.73; 95% CI, .55-.97) and gram-negative organisms (0.51; .33-.78) but not yeast (0.90; .49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03 hours (95% CI, -8.60 to -1.45 hours), and length of stay decreased by -2.48 days (-3.90 to -1.06 days). Conclusions. For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship programs (ASPs) have the potential to improve patient outcomes, decrease microbial resistance, increase patient safety, and decrease costs. However, to justify the costs involved with providing an ASP, it is necessary to assess its impact in achieving these outcomes on an ongoing basis. Objective: The purpose of this study was to characterize the overall impact of the ASP at an academic medical center. Methods: Quasi-experimental, before and after stewardship program implementation, retrospective analyses of quarterly antimicrobial utilization, bacterial susceptibilities, and antibiotic acquisition costs were utilized. Results: Mean stewardship-focused antibiotic utilization was 510.3 defined daily doses (DDD) per 1,000 patient days for the pre-ASP period and 426.4 DDD per 1,000 patient days for the ASP period (16.4% decrease; p < .001). Significant changes in Pseudomonas aeruginosa susceptibility to tobramycin (8% increase; p = .006) and piperacillin-tazobactam (8% decrease; p = .024) were noted. Changes in susceptibility of Staphylococcus aureus to methicillin (7% increase, p = .012) were also observed. ASP-focused antibiotic expenditures decreased from $4,028,068 in fiscal year (FY) 2010 to $2,135,173 in FY2013 (p = .01). Conclusions: ASP initiatives were associated with an observed reduction in stewardship-focused antibiotic utilization. Significant changes in susceptibilities of some bacteria were noted but did not seem to consistently reflect antibiotic utilization changes. Significant decreases in antimicrobial expenditures were observed. Observed outcomes are temporally related to shifts in antimicrobial selection through the initiation of stewardship program-driven antibiotic policy changes. These outcomes have been used to justify and expand our stewardship program moving forward. [ABSTRACT FROM AUTHOR]

A recent study led by the Centers for Disease Control and Prevention (CDC) revealed at least 30% of antibiotic prescriptions in the outpatient setting were inappropriate. In this study of all ages, among adult patients, results were similar to the overall population, with the majority of inappropriate prescribing relating to respiratory infections. We applied the same methodology to investigate rates of antibiotic prescribing for respiratory tract infections in outpatient primary care clinics at the Providence Veterans Affairs Medical Center. The results of our evaluation reflected comparable rates of inappropriate prescribing, but when stratified by teaching versus nonteaching primary care clinics, inappropriate prescribing was significantly higher in non-teaching clinics (17.6% vs 44.0%, p < .0001). Respiratory infection visits in non-teaching outpatient clinics may be a pragmatic target for antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Among critically ill COVID-19 patients, bacterial coinfections may occur, and timely appropriate therapy may be limited with culture-based microbiology due to turnaround time and diagnostic yield challenges (e.g. antibiotic pre-exposure). We performed a systematic review and meta-analysis of the impact of BioFire® FilmArray® Pneumonia Panel in detecting bacteria and clinical management among critically ill COVID-19 patients admitted to the ICU. Seven studies with 558 patients were included. Antibiotic use before respiratory sampling occurred in 28-79% of cases. The panel incidence of detections was 33% (95% CI 0.25 to 0.41, I2=32%) while culture yielded 18% (95% CI 0.02 to 0.45; I2=93%). The panel was associated with approximately a 1 and 2 day decrease in turnaround for identification and common resistance targets, respectively. The panel may be an important tool for clinicians to improve antimicrobial use in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection causing significant morbidity and mortality in immunocompromised patients. The conventional treatment of PJP is sulfamethoxazole‐trimethoprim (SMX‐TMP) dosed at 15–20 mg/kg/day of the trimethoprim component. Several studies have suggested similar mortality outcomes and an improved adverse effect profile using a lower dose (<15 mg/kg/day) SMX‐TMP regimen. Our objective of this meta‐analysis was to evaluate the safety and efficacy of lower dose SMX‐TMP for PJP pneumonia. Methods: We conducted a systematic review and meta‐analysis of the existing literature according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. MEDLINE and Embase databases were searched from inception to January 15, 2020, for studies in English evaluating low‐dose SMX‐TMP (<15 mg/kg/day) compared to conventional dosing for the treatment of PJP. Outcomes evaluated in our meta‐analysis include survival and adverse reactions. Results: After excluding studies that did not meet our inclusion criteria, four studies were analyzed for adverse reactions and three for mortality. Overall, there was no significant difference in mortality between low‐dose and conventional‐dose SMX‐TMP groups (relative risk [RR]: 0.55, 95% confidence interval [CI], 0.18–1.70). There was a significant decrease in the rate of adverse reactions for the low‐dose group compared with the conventional‐dose group (RR: 0.70, 95% CI, 0.53–0.91). Conclusions: This meta‐analysis shows a significant decrease in adverse reactions and similar mortality rates with lower‐dose SMX‐TMP compared to conventional dosing. A low‐dose SMX‐TMP regimen in the treatment of PJP should be considered a viable option as it could potentially decrease treatment discontinuation rates and reduce patient harm. [ABSTRACT FROM AUTHOR]

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) are commonly used in clinical practice for gastric acid suppression. However, these agents have also been associated with certain negative clinical outcomes. We evaluated the real-world effects of incident PPI use on clinical outcomes in patients with Staphylococcus aureus bacteremia. Methods: This retrospective cohort study included patients admitted to Veterans Affairs hospitals with positive S. aureus blood cultures collected between 2002 and 2013 that received appropriate antibiotics within 48 hours of culture collection. Clinical outcomes among three PPI exposure groups, each compared to nonusers, were assessed with propensity-score-matched Cox proportional-hazard regression models: pretreated PPI users initiating therapy in the 30 days prior to culture and either (a) continuing PPI therapy after culture, or (b) not continuing after culture, and (c) de novo users initiating at culture. Results: Clinical outcomes, including inpatient mortality, intensive care discharge, 30-day mortality, 30-day readmission, and 30-day Clostridium difficile infection (CDI) were similar among PPI users and nonusers. Though length of stay was longer in pretreated, continuing PPI users [time-to-discharge hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.65–0.93], 14-day mortality was significantly lower than in nonusers (HR 0.66, 95% CI 0.50–0.87). Conclusions: In our large national cohort study, PPIs were not associated with an increased risk of negative clinical outcomes, including mortality and CDI, in patients with S. aureus bacteremia. [ABSTRACT FROM AUTHOR]

Antimicrobial stewardship (AMS) programs integrated with rapid diagnostic tests optimize patient outcomes and reduce time to effective therapy (TTET) and time to optimal therapy (TTOT). This study identifies predictors of TTET and TTOT among patients with positive blood cultures and identifies limitations to current TTOT definitions and outcomes. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) are commonly used in clinical practice for gastric acid suppression. However, these agents have also been associated with certain negative clinical outcomes. We evaluated the real-world effects of incident PPI use on clinical outcomes in patients with Staphylococcus aureus bacteremia. Methods: This retrospective cohort study included patients admitted to Veterans Affairs hospitals with positive S. aureus blood cultures collected between 2002 and 2013 that received appropriate antibiotics within 48 hours of culture collection. Clinical outcomes among three PPI exposure groups, each compared to nonusers, were assessed with propensity-score-matched Cox proportional-hazard regression models: pretreated PPI users initiating therapy in the 30 days prior to culture and either (a) continuing PPI therapy after culture, or (b) not continuing after culture, and (c) de novo users initiating at culture. Results: Clinical outcomes, including inpatient mortality, intensive care discharge, 30-day mortality, 30-day readmission, and 30-day Clostridium difficile infection (CDI) were similar among PPI users and nonusers. Though length of stay was longer in pretreated, continuing PPI users [time-to-discharge hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.65–0.93], 14-day mortality was significantly lower than in nonusers (HR 0.66, 95% CI 0.50–0.87). Conclusions: In our large national cohort study, PPIs were not associated with an increased risk of negative clinical outcomes, including mortality and CDI, in patients with S. aureus bacteremia. [ABSTRACT FROM AUTHOR]

Background Bloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance. Methods This was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene. Results Four hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%–81% using the scoring tools (P  < .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%–71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%–12%). Conclusions Verigene significantly outperformed published ESBL scoring tools for identifying CRO-resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy. [ABSTRACT FROM AUTHOR]

Background: The Veterans Affairs (VA) is a leader in the implementation and advancement of antibiotic stewardship programs throughout the nation. The Centers for Disease Control and Prevention (CDC) has also led national antibiotic stewardship efforts and has outlined core elements to improve antibiotic use in hospitals, long-term care, and outpatient settings. Many facilities still face challenges to the implementation and maintenance of successful programs, particularly in nonacute care settings. The objective of this study was to identify barriers and facilitators to antibiotic stewardship within the VA medical centers through qualitative interviews with pharmacists. Methods: Eight semi-structured telephone interviews were conducted with pharmacists from 6 VA medical centers within VA New England Healthcare System. Pharmacist respondents were either pharmacy champions (for medical centers with established programs) or pharmacists with responsibilities in making antibiotic recommendations (locations without established programs). All interviews were audio recorded and transcribed verbatim. NVivo 8 was used for data coding and analysis. Results: Pharmacists from all 8 medical centers were contacted for interviews and pharmacists from 6 medical centers agreed to interviews (75% VA New England medical center participation). Three main themes regarding antibiotic stewardship were identified from the interviews with pharmacists. Respondents described the importance of (1) a supportive organizational culture, (2) protected time for antibiotic stewardship, and (3) a cohesive organizational structure in the success of antibiotic stewardship programs. Conclusions: Our findings support the CDC core elements for antibiotic stewardship, in particular the importance of leadership commitment in the creation of a culture that supports antibiotic stewardship and in ensuring staff are given sufficient time for antibiotic stewardship efforts. Although a strong supportive culture has been built, strategies focused on fostering increased protected time for antibiotic stewardship and a cohesive organizational structure may be helpful in advancing and sustaining successful antibiotic stewardship programs that improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background Although existing literature supports durations of 5–7 days for skin and soft tissue infections (SSTIs), longer durations are commonly used. Obesity and heart failure (HF) have been associated with increased risk for treatment failure of SSTIs; however, whether prolonged antibiotic durations reduce the risk of treatment failure is unknown. We evaluated practice patterns for SSTIs in patients with obesity and/or HF and whether short antibiotic durations (≤8 days) were associated with treatment failure. Methods We performed a single-center, retrospective cohort study of inpatients between January 1, 2006, and December 30, 2016, with SSTIs based on International Classification of Diseases (ICD) coding, and obesity and/or HF. Charts were manually reviewed to collect demographic, clinical, treatment, and outcome data. Propensity score matching was used to estimate the risk of treatment failure between the 2 groups. Secondary outcomes included length of stay, 30-day readmission, and Clostridium difficile infection rates. Results A total of 207 patients were included. Forty-nine (23.7%) received a short antibiotic duration and 158 (76.3%) a long duration. The median duration of therapy (interquartile range [IQR]) was 7 (7–8) days in the short group and 14 (10–15) days in the long group. In the propensity score–matched cohort, 28 (28.6%) treatment failures occurred in the long group, as compared with 5 (10.2%) in the short group (P =.02), as well as a shorter length of stay (IQR) in the short- vs long-duration group (2 [2–3] vs 3 [2–5] days, respectively; P =.002). There was no difference in other secondary outcomes. Conclusions The majority of patients with obesity or HF received a longer antibiotic course for SSTIs; however, a longer antibiotic course was not associated with lower treatment failure rates. Higher failure rates in the long-duration group may be reflective of clinical decisions made in the face of diagnostic uncertainty and warrant further evaluation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Acute infectious gastroenteritis (AGE) is a common reason for outpatient visits and hospitalizations in the United States. This study aimed to understand the demographic and clinical characteristics, common pathogens detected, health care resource utilization (HRU), and cost among adult outpatients with AGE visiting US health systems. METHODS: A retrospective cohort study was conducted using one of the largest hospital discharge databases (PINC AI Healthcare Database) in the United States. Adult patients (aged ‡18 years) with a principal diagnosis of AGE during an outpatient visit between January 1, 2016, and June 30, 2021, were included. Pathogen detection analysis was performed in those with microbiology data available. RESULTS: Among 248,896 patients, the mean age was 44.3 years (range 18–891 years), 62.9% were female, and 68.5% were White. More than half (62.0%) of the patients did not have any preexisting comorbidity, and only 18.3% underwent stool workup at the hospital. Most patients (84.7%) were seen in the emergency department, and most (96.4%) were discharged home. Within 30 days of discharge, 1.0% were hospitalized, and 2.8% had another outpatient visit due to AGE. The mean cost of the index visit plus 30-day AGE-related follow-up was $1,338 per patient, amounting to $333,060,182 for the total study population. Among patients with microbiology data available (n 5 12,469), common pathogens detected were Clostridioides difficile (32.2%), norovirus (6.3%), and Campylobacter spp. (4.0%). DISCUSSION: AGE is a common and costly disease affecting adults of all ages and more females than males, including individuals with or without baseline conditions in a hospital-based outpatient setting. C. difficile was the most common pathogen detected. [ABSTRACT FROM AUTHOR]

Study Objective: Bloodstream infections (BSIs) are a significant cause of mortality. Use of a rapid multiplex polymerase chain reaction‐based blood culture identification panel (BCID) may improve antimicrobial utilization and clinical outcomes by shortening the time to appropriate therapy and de‐escalating antibiotics among patients on overly broad‐spectrum empiric therapy. The effect of BCID on clinical outcomes across varying institutional antimicrobial stewardship program (ASP) practices is unclear. This study evaluated clinical outcomes associated with the "real‐world" implementation of BCID in a national health system with varying ASP practices. Design: National, multicenter, retrospective, pre–post quasi‐experimental study of hospitalized patients admitted from 2015 to 2020 to VHA facilities, which introduced the BCID for ≥1 year. Setting: United States Veterans Health Administration (VHA) hospitals with BCID. Patients Hospitalized VHA patients with ≥1 blood culture positive for bacteria featured on the BCID panel. Intervention: Comparison of outcomes between the pre‐ and post‐BCID implementation groups. Measurements Outcomes evaluated included early antimicrobial de‐escalation within 48 h, defined as reduction in antimicrobial spectrum scores, time to appropriate therapy, and 30‐day mortality. Main Results A total of 4138 patients (pre‐BCID, n = 2100; post‐BCID, n = 2038) met the study criteria. Implementation of BCID was associated with significant improvements in early antimicrobial de‐escalation (34.6%: pre‐BCID vs. 38.1%: post‐BCID; p = 0.022), which persisted after adjusting for other covariates (adjusted risk ratio [aRR], 1.11; 95% confidence interval [CI], 1.02–1.20; p = 0.011). Median time to appropriate therapy was shorter in the post‐BCID implementation group relative to the pre‐BCID group (9 h: pre‐BCID vs. 8 h: post‐BCID, respectively, p = 0.005), and a greater percentage of patients received early appropriate antimicrobial therapy within 48 h in the post‐BCID implementation group (91.7%: pre‐BCID vs. 93.8%: post‐BCID; p = 0.008). In the multivariable regression analysis, BCID implementation was significantly associated with a higher likelihood of appropriate therapy within 48 h (aRR, 1.02; 95% CI, 1.01–1.08; p = 0.020). There was no difference in 30‐day mortality between groups overall (12.6% pre‐BCID vs. 11.2% post‐BCID; p = 0.211). Conclusions: In a "real‐world" clinical setting, the implementation of BCID was associated with clinical improvements in antimicrobial utilization. The BCID platform may serve as a useful adjunct for BSI management in facilities with ASP. [ABSTRACT FROM AUTHOR]

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision making using selected patient-centered vignettes, and make recommendations for future studies to advance the field. [ABSTRACT FROM AUTHOR]

Background Vancomycin is now a preferred treatment for all cases of Clostridioides difficile infection (CDI), regardless of disease severity. Concerns remain that a large-scale shift to oral vancomycin may increase selection pressure for vancomycin-resistant Enterococci (VRE). We evaluated the risk of VRE following oral vancomycin or metronidazole treatment among patients with CDI. Methods We conducted a retrospective cohort study of patients with CDI in the US Department of Veterans Affairs health system between 1 January 2006 and 31 December 2016. Patients were included if they were treated with metronidazole or oral vancomycin and had no history of VRE in the previous year. Missing data were handled by multiple imputation of 50 datasets. Patients treated with oral vancomycin were compared to those treated with metronidazole after balancing on patient characteristics using propensity score matching in each imputed dataset. Patients were followed for VRE isolated from a clinical culture within 3 months. Results Patients treated with oral vancomycin were no more likely to develop VRE within 3 months than metronidazole-treated patients (adjusted relative risk, 0.96; 95% confidence interval [CI],.77 to 1.20), equating to an absolute risk difference of −0.11% (95% CI, −.68% to.47%). Similar results were observed at 6 months. Conclusions Our results suggest that oral vancomycin and metronidazole are equally likely to impact patients' risk of VRE. In the setting of stable CDI incidence, replacement of metronidazole with oral vancomycin is unlikely to be a significant driver of increased risk of VRE at the patient level. In this multicenter, retrospective cohort study of patients with Clostridioides difficile infection, the use of oral vancomycin did not increase the risk of vancomycin-resistant Enterococci infection at 3 or 6 months compared to metronidazole. [ABSTRACT FROM AUTHOR]

Background. Recent literature has highlighted methicillin-resistant Staphylococcus aureus (MRSA) nasal screening as a possible antimicrobial stewardship program tool for avoiding unnecessary empiric MRSA therapy for pneumonia, yet current guidelines recommend MRSA therapy based on risk factors. The objective of this meta-analysis was to evaluate the diagnostic value of MRSA nasal screening in MRSA pneumonia. Methods. PubMed and EMBASE were searched from inception to November 2016 for English studies evaluating MRSA nasal screening and development of MRSA pneumonia. Data analysis was performed using a bivariate random-effects model to estimate pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results. Twenty-two studies, comprising 5163 patients, met our inclusion criteria. The pooled sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types were 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA pneumonia, the calculated PPV was 44.8%, and the NPV was 96.5%. The pooled sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) were 85% and 92.1%, respectively. For CAP and HCAP both the PPV and NPV increased, to 56.8% and 98.1%, respectively. In comparison, for MRSA ventilated-associated pneumonia, the sensitivity, specificity, PPV, and NPV were 40.3%, 93.7%, 35.7%, and 94.8%, respectively. Conclusion. Nares screening for MRSA had a high specificity and NPV for ruling out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, MRSA nares screening is a valuable tool for AMS to streamline empiric antibiotic therapy, especially among patients with pneumonia who are not colonized with MRSA. [ABSTRACT FROM AUTHOR]

Background Recent studies in gram-negative bacteremia (GNB) suggest that intravenous (IV) to oral (PO) switch and short treatment durations yield similar clinical outcomes and fewer adverse events. Antimicrobial stewardship program (ASP) bundled initiatives have been associated with improved clinical outcomes for bloodstream infections. Methods This single-center retrospective cohort evaluation included inpatient adults from 11/2014–10/2015 and 10/2017–9/2018 with GNB. The pre-ASP period was before the establishment of an ASP program. In the post period, the ASP promoted IV-to-PO switches, avoidance of repeat blood cultures, and short treatment durations for patients with uncomplicated GNB. The primary outcome was duration of antibiotic therapy. Secondary outcomes included process measures associated with the bundle and clinical outcomes. Results One hundred thirty-seven patients met criteria for inclusion, with 51 patients in the pre group and 86 patients in the post group. Background characteristics were similar between groups. The median duration of therapy (interquartile range) was 14 (10–16) days in the pre group and 10 days (7–14) in the post group (P <.001). The median day of IV-to-PO switch was day 5 (4–6) in the pre group vs day 4 (3–5) in the post group (P =.046). The average total hospital cost per case decreased by 27% in the post group (P =.19). Mortality rates and bacteremia recurrence were not significantly different between groups. Conclusions An ASP bundle for uncomplicated GNB was associated with reduced durations of therapy and earlier PO switch. These findings highlight the synergistic role of ASPs in optimizing antibiotic use and promoting patient safety. [ABSTRACT FROM AUTHOR]

Background Limited and conflicting data exist evaluating low-bioavailability oral antibiotics (LOW) for definitive treatment of Enterobacteriaceae bacteremia (EB), and existing dogma limits their use. We compared outcomes for EB from a suspected urine source with LOW vs. high-bioavailability oral antibiotics (HIGH). Methods This was a retrospective cohort study across Veterans Affairs hospitals from 2006 to 2015. Inclusion criteria were monomicrobial EB and matching urine culture; receipt of active, empiric parenteral antibiotic(s); and conversion to a single oral LOW or HIGH between treatment day 2 and 6. Exclusion criteria were EB in the previous year, prior urologic abscess, or chronic prostatitis. HIGH included fluoroquinolones or trimethoprim-sulfamethoxazole. LOW included oral β-lactams. The primary outcome was all-cause 30-day mortality or recurrent EB. Patients were weighted using propensity-based overlap weights to make the groups more similar to each other at baseline. Log binomial regression models were used to estimate relative risks and risk differences. Results A total of 4,090 patients met inclusion criteria with 955 LOW and 3,135 HIGH. The median days of parenteral antibiotics before conversion to oral antibiotics were 4 (IQR 3, 5) in LOW and 4 (IQR 3, 4) in HIGH. The composite primary outcome occurred in 42 (4.4%) LOW and 94 (3.0%) HIGH. The adjusted relative risk (aRR) of the composite primary outcome with LOW was 1.28 (95% CI 0.86–1.89; risk difference [RD] 0.9%). Recurrent EB within 30-days occurred in 14 (1.5%) LOW and 12 (0.4%) HIGH (aRR 3.24, 95% CI, 0.46–22.8; RD 1.0%). Thirty-day mortality occurred in 29 (3.0%) LOW and 82 (2.6%) HIGH (aRR 1.0, 95% CI, 0.66–1.52; RD 0%). Similar outcomes were observed at 90 days. Conclusion There was no difference in the composite outcome of 30-day mortality and recurrent bacteremia comparing hospitalized patients who received LOW vs. HIGH for the definitive treatment of EB from a suspected urine source. While there was a nonsignificantly higher risk of 30-day recurrent EB with LOW, the absolute risk and risk difference were small, suggesting that definitive therapy with LOW may be considered. Future evaluation is needed to better understand risk factors for recurrent EB and which patients may fail LOW. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]