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Importance: Our study addresses a significant issue in the medical and scientific community-the delayed administration of appropriate antimicrobial treatments due to the time-consuming process of phenotypic susceptibility data collection in gram-negative bloodstream infections. Our research indicates that a multiplex PCR rapid diagnostic test (RDT) significantly outperformed two clinical scoring tools in predicting ceftriaxone susceptibility. Multiplex PCR also led to reduced instances of undertreatment with ceftriaxone and minimized overtreatment with carbapenems. Furthermore, multiplex PCR demonstrated high sensitivity and specificity in predicting ceftriaxone susceptibility. The results of our study underscore the potential RDTs to reduce the time to appropriate antimicrobial therapy, leading to improved patient outcomes and reduced healthcare costs., Competing Interests: Tristan T. Timbrook is an employee and stockholder of BioMérieux. No other authors have any financial disclosures.

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., (© 2022 Pharmacotherapy Publications, Inc.)

Purpose: As changes in antibiotic therapy are common, intent-to-treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia., Methods: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002-September 2015) and community hospitals (de-identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009-March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum-Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia., Results: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes., Conclusions: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent-to-treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research., (© 2019 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.)

Background: Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims., Content: This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed., Summary: Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact., (© 2018 American Association for Clinical Chemistry.)

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., Competing Interests: DisclosuresDr. Hurst has received honorarium and travel expenses from bioMerieux and BioFire Diagnostics. Dr. Timbrook has received honorarium as a speaker and/or advisor for BioFire Diagnostics and GenMark Diagnostics. The authors have declared no other potential conflicts of interest., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

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., (© 2017 Pharmacotherapy Publications, Inc.)

In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in Staphylococcus aureus bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive S. aureus blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii) de novo users initiating at culture. Nonusers included patients without statins in the year prior to culture through discharge. Propensity score-matched Cox proportional hazards regression models were developed. We were able to balance significantly different baseline characteristics using propensity score matching for pretreated without continuation ( n = 331), pretreated with continuation ( n = 141), and de novo ( n = 177) statin users compared to nonusers. We observed a significantly lower 30-day mortality rate (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.25 to 0.84; number needed to treat [NNT], 10) among pretreated and continued statin users, while protective effects were not observed in de novo (HR, 1.04; 95% CI, 0.60 to 1.82; NNT, undefined) or pretreated but not continued (HR, 0.92; 95% CI, 0.64 to 1.32; NNT, 47) users. In our national cohort study among patients with S. aureus bacteremia, continuation of statin therapy among incident statin users was associated with significant beneficial effects on mortality, including a 54% lower 30-day mortality rate., (Copyright © 2017 American Society for Microbiology.)

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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]

Enterobacteriaceae bacteremia, particularly when associated with antimicrobial resistance, can result in increased mortality, emphasizing the need for timely effective therapy. Clinical risk prediction models are promising tools, stratifying patients based on their risk of resistance due to ESBL and carbapenemase-producing Enterobacteriaceae in bloodstream infections (BSIs) and, thereby, improving therapeutic decisions. This systematic review and meta-analysis synthesized the literature on the performance of these models. Searches of PubMed and EMBASE led to the identification of 10 relevant studies with 6106 unique patient encounters. Nine studies concerned ESBL prediction, and one focused on the prediction of carbapenemases. For the two ESBL model derivation studies, the discrimination performance showed sensitivities of 53–85% and specificities of 93–95%. Among the four ESBL model derivation and validation studies, the sensitivities were 43–88%, and the specificities were 77–99%. The sensitivity and specificity for the subsequent external validation studies were 7–37% and 88–96%, respectively. For the three external validation studies, only two models were evaluated across multiple studies, with a pooled AUROC of 65–71%, with one study omitting the sensitivity/specificity. Only two studies measured clinical utility through hypothetical therapy assessments. Given the limited evidence on their interventional application, it would be beneficial to further assess these or future models, to better understand their clinical utility and ensure their safe and impactful implementation. [ABSTRACT FROM AUTHOR]

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]

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]

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]