Early De-escalation Research Articles

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length >60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

A multicenter evaluation of a novel microfluidic rapid AST assay for Gram-negative bloodstream infections.

Increasing antimicrobial resistance underscores the need for new diagnostic solutions to guide therapy, but traditional antimicrobial susceptibility testing (AST) is often inadequate in time-critical diseases such as sepsis. This work presents a novel and rapid AST system with a rapid turnaround of results, which may help reduce the time to guided therapy, possibly allowing early de-escalation of broad-spectrum empirical therapy as well as rapid adjustments to treatments when coverage is lacking.

432 Pneumococcal Urinary Antigen Testing in Community Acquired Pneumonia: A Missed Opportunity for Early Antibiotic De-Escalation or a Low-Value Test?

432 Pneumococcal Urinary Antigen Testing in Community Acquired Pneumonia: A Missed Opportunity for Early Antibiotic De-Escalation or a Low-Value Test?

Early antibiotic de-escalation in patients with severe infections due to bloodstream infection by enterobacterales: A post hoc analysis of a prospective multicentre cohort

Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting. Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18-0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32-0.83), and extended-spectrum β-lactamase (ESBL)-producing isolate (aOR = 0.28; 95% CI = 0.17-0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56-3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39-2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09-1.06). Matched and inverse probability treatment weighting analysis showed similar results. These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Opportunity for Early De-escalation in Enterobacterales Bacteremia with Rapid Blood Culture Identification Technology

Background: The BioFire FilmArray Blood Culture Identification 2 (BCID2) Panel is used to identify organisms present in positive blood cultures within hours of detection at Virginia Commonwealth University Health System (VCUHS). BCID2 is also able to detect common resistance mechanisms including CTX-M, the most common extended-spectrum beta-lactamase (ESBL) in the United States, and several carbapenemases. The Antimicrobial Stewardship Program (ASP) at VCUHS established optimal treatment recommendations for each organism identified by BCID2 based on the detection of a resistance mechanism and local resistance patterns. The recommendation for the majority of Enterobacterales without a detected resistance mechanism is ceftriaxone. However, providers are often reluctant to de-escalate antibiotics without confirmed susceptibility testing, as there may be other mechanisms of antibiotic resistance in Gram-negative organisms. The objective of this evaluation was to measure the degree of congruence between BCID2 resistance mechanism detection and susceptibility testing by disk diffusion, and to validate the adequacy of the VCUHS ASP BCID2 treatment recommendations for Enterobacterales bacteremia. Methods: Patients with positive Enterobacterales BCID2 results from March 12 to June 19, 2023 were retrospectively identified. Organisms identified by BCID2 that were considered high-risk for clinically significant AmpC production due to an inducible AmpC gene (i.e., K. aerogenes, E. cloacae complex) were excluded. Results: A total of 270 results were included. The most commonly identified organism was E. coli (n = 139, 51.5%), followed by K. pneumoniae (n = 74, 27.4%). There were 27 (10%) isolates positive for CTX-M and 1 (0.4%) isolate positive for KPC. All CTX-M isolates were ceftriaxone resistant, and the KPC isolate was meropenem resistant. The remaining 242 isolates were negative for all resistance markers detected by BCID2. Of these, only 3 (1.2%) were resistant to ceftriaxone and notably, 8 (3.3%) were resistant to piperacillin/tazobactam. Overall, BCID2 CTX-M detection was 90% sensitive and 100% specific for predicting ceftriaxone resistance in Enterobacterales. Conclusion: CTX-M detection by BCID2 is highly sensitive and specific for predicting ceftriaxone resistance in Enterobacterales. CTX-M negative isolates were more often susceptible to ceftriaxone than to piperacillin/tazobactam, which is commonly used as empiric therapy for Gram-negative organisms at our institution. This highlights an excellent opportunity for safe and effective early de-escalation of antibiotics for treatment of Enterobacterales bacteremia.

FilmArray Meningitis/Encephalitis Panel Impact on Antibiotic Usage in Patients with Suspected Community-Acquired Meningitis

Background: Cerebrospinal fluid (CSF) cultures are commonly performed to evaluate patients with suspected bacterial meningitis. These cultures, however, can take up to 72 hours, leading to delays in antibiotic de-escalation and increased antimicrobial utilization. The turnaround for the BioFire® FilmArray® Meningitis/Encephalitis(FA/ME) panel is less than an hour, which may facilitate early de-escalation. Our study aimed to assess whether the use of FA/ME panels in combination with CSF cultures could impact antimicrobial therapy compared to cultures alone in patients treated for suspected bacterial meningitis. Methods: Our retrospective study included patients from five hospitals in Texas (2017-2023) who received empiric antibiotics for suspected community-acquired meningitis and underwent a lumbar puncture within 96 hours of admission. Patients with ventricular drains, traumatic brain injury, and non-central nervous system infections were excluded. Cases comprised patients who had an FA/ME panel performed, while controls included patients without the panel. Outcomes were defined as the empiric duration of antimicrobial therapy (days) and total days of antibiotic therapy (DOT). Wilcoxon Rank Sum test and multiple linear regression models were applied to assess the relationship between the use of the FA/ME panel and study outcomes. Independent variables comprised demographics, institution type, acuity, clinical presentation, CSF values, and FA/ME panel use. Imputation was performed using multiple imputation by chained equations. Results: A total of 193 patients were included in our study. Seventy-one patients received the FA/ME panel (along with the CSF culture), while 122 patients received the CSF culture alone (controls). The median empiric duration of antibiotic therapy in the cases and controls were 1.71 days and 1.18 days, respectively (p = .160). The median DOT in the cases and controls were eight days and six days, respectively (p = .045). After adjusting for confounders, the FA/ME panel was not significantly associated with changes in the empiric duration of antibiotic therapy (B= 0.18, p = .669, Figure 1) or DOT (B= 1.28, p = .170, Figure 2).Conclusion: Providing FA/ME panel testing without active antimicrobial stewardship interventions did not result in a change in antimicrobial prescribing patterns. The difference from prior literature could be explained by the smaller sample size, limiting the power of the study. Further prospective antimicrobial stewardship efforts should focus on training providers on interpreting FA/ME panel results and providing prospective audits and feedback.

Association of antibiotics with the outcomes in COVID-19 pneumonia patients with elevated PCT levels

ObjectiveTo assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. MethodsThis retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients’ antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. ResultsOur cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %).Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. ConclusionOur study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

P2Y12 monotherapy versus standard dual antiplatelet therapy after percutaneous coronary intervention: a systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor after percutaneous coronary intervention (PCI) is the recommended therapy for lowering the ischemic risk among patients with acute coronary syndrome (ACS). However, the increased incidence of bleeding is a major concern. Monotherapy with a P2Y12 inhibitor after short-term DAPT to reduce adverse cardiovascular events and bleeding rates has not been fully established and remains uncertain. This meta-analysis aims to determine the effectiveness of P2Y12 inhibitor monotherapy after short-term DAPT in reducing cardiovascular and bleeding events. Methods A comprehensive search of randomized controlled trials (RCTs) examining the use of short-term DAPT followed by P2Y12 monotherapy in patients with ACS who underwent PCI was conducted. Outcome measures for all-cause mortality, myocardial infarction, and bleeding rates were analyzed using a random-effects model via Review Manager V5.4. Results A total of six randomized controlled trials (RCTs) with 36,724 subjects were analyzed. There were no significant differences in all-cause mortality (RR 0.89 [95% CI: 0.78-1.02], I² = 0%, p = 0.10) and myocardial infarction (RR 1.00 [95% CI: 0.88-1.14], I² = 0%, p = 0.72) between the P2Y12 inhibitor group and dual antiplatelet therapy (DAPT) group. There was a lower rate of major bleeding in the P2Y12 group compared to the DAPT group (RR 0.65 [95% CI: 0.49-0.88], I² = 76%, p = 0.002). The major sources of substantial heterogeneity are due to different intervals of de-escalation and baseline risk factors prior to PCI in each study. Conclusion P2Y12 monotherapy has similar rates of all-cause mortality and myocardial infarction. However, early de-escalation leads to a lower incidence of bleeding. P2Y12 monotherapy showed a 35% decreased risk of bleeding compared to the DAPT strategy. This suggests that P2Y12 monotherapy is a preferable antiplatelet strategy in patients undergoing PCI, especially in the high-risk bleeding population.

Characterization of initial CLABSI culture results to support antimicrobial de-escalation in pediatric GI inpatients.

Central Line-associated Bloodstream Infections (CLABSIs) pose a serious mortality and morbidity risk. An institutional protocol was developed for the evaluation and empirical antibiotic treatment of possible CLABSIs. The potential impact of de-escalating antimicrobial therapy based on initial Gram stain and molecular identification was assessed. All positive blood cultures from patients admitted to the gastroenterology service at a large pediatric medical center were collected from 1/1/14 to 12/31/20. Cultures that were negative, repeated, or causative organisms that were unable to be identified with susceptibility data were excluded. Timepoints and organism(s) from each culture were recorded. Polymicrobial cultures were classified as containing only gram-positive organisms (polymicrobial GP), only gram-negative organisms (polymicrobial GN), or mixed spectrum. During the 6-year period, 361 positive blood cultures were included in the study. Single isolates were identified in 79.5% (287/361) of cultures. Polymicrobial cultures from confirmed central line source accounted for 15.0% (54/361), with 6.4% (23/361) Polymicrobial GP, 4.4% (16/361) Polymicrobial GN, and 4.2% (15/361) being mixed-spectrum cultures. Both organism types were detected on initial gram-stain in 40% (6/15) of the mixed-spectrum cultures, another 26.7% (4/15) had the opposite-spectrum organism identified within an average of <3 h and the remaining 33.3% (5/15) had the opposite-spectrum organism identified by culture growth. Polymicrobial mixed-spectrum cultures accounted for <5% of positive blood cultures and most isolates were identified within 3 h of first positivity. This may allow for further investigation of early de-escalation of therapy for this population and limit antimicrobial exposure.

Evaluation of Post-thrombolytic Events to Determine Appropriate ICU Monitoring Duration for Patients with Ischemic Stroke.

Standard treatment for eligible patients presenting with acute ischemic stroke (AIS) is thrombolysis with tissue plasminogen activators alteplase or tenecteplase. Current guidelines recommend monitoring patients in an intensive care unit (ICU) for 24h after thrombolytic therapy. However, recent studies have questioned the need for prolonged ICU monitoring. This retrospective cohort study aims to identify potential candidates for early transition to a lower level of care by assessing risk factors for neurological deterioration, symptomatic intracranial hemorrhage (sICH), or need for ICU intervention within 24h post-thrombolysis. This retrospective cohort study included adult patients 18years and older with AIS who received thrombolysis. Patients were excluded if they were transferred to another facility, if they were transitioned to comfort care or hospice care within 24h, or if they lacked imaging and National Institutes of Health Stroke Scale (NIHSS) score data. The primary end point was incidence of sICH between 0-12 and 12-24h. Secondary end points included the need for ICU intervention and rates of neurological deterioration. The analysis included 204 patients who received the full dose of alteplase. Among them, ten patients (4.9%) developed sICH, with the majority (n = 7) occurring within 12h post-thrombolysis. Sixty-two patients required ICU interventions within 12h compared with four patients after 12h. Twenty-four patients had neurological deterioration within 12h, and seven patients had neurological deterioration after 12h. Multivariable analysis identified mechanical thrombectomy and increased blood pressure at presentation as predictors of ICU need beyond 12h post-thrombolysis. Our study demonstrates that sICH, neurological deterioration, and need for ICU intervention rarely occur beyond 12h after thrombolytic administration. Patients presenting with blood pressures < 140/90mm Hg, NIHSS scores < 10, and not undergoing mechanical thrombectomy may be best candidates for early de-escalation. Larger prospective studies are needed to more fully evaluate the safety, feasibility, and financial impact of early transition out of the ICU.

709 Establishment of an Early ICU De-escalation Pathway Using the Modified Frailty Index Among Angiogram-Negative Subarachnoid Hemorrhage Patients

INTRODUCTION: Angiogram-negative subarachnoid hemorrhage (ANSAH) may have a benign clinical course. Our standard practice is to observe ANSAH patients for a prolonged period in the ICU. Previous work has established frailty as a strong predictor of ANSAH outcomes. METHODS: A retrospective cohort analysis was performed among patients admitted between 2011 and 2022 with non-traumatic subarachnoid hemorrhage and initial angiogram (DCA) negative for source. Primary endpoints were in-hospital complications, discharge home, and length-of-stay (LOS). Cost analysis was performed using hospital charges. RESULTS: 101 patients were included with an average age of 59.7 ±1.2 years, Hunt and Hess score of 2.0 ± 0.1, and 51 (50.5%) with a perimesencephalic hemorrhage distribution. 2 patients had a subsequent DCA showing aneurysmal etiology, both of whom would have been considered high risk. 38 (37.6%) were frail, 38 (37.6%) required an EVD, and 68 (67.3%) were intact on arrival. Multivariate analysis showed that frailty but not age or perimesencephalic distribution predicted the 3 primary endpoints (p &lt; 0.039) while lack of EVD predicted LOS (p = 0.004) and intact neurologic exam predicted discharge home (p = 0.043). Low-risk patients (40/101, 39.6%) had no deaths, significantly reduced odds of any complication (OR 0.14, 95%CI: 0.04-0.44, p &lt; 0.001), increased odds of discharge home (OR 9.98; 95%CI: 2.19-45.46, p &lt; 0.001), and shorter LOS (7.8 ± 0.4 v. 14.7 ± 1.1 days, p &lt; 0.001). Assuming a 6-day ward stay after 1-day of ICU observation, early de-escalation of low-risk ANSAH patients would, on average, save $20,177.70 per patient. CONCLUSIONS: Non-frail ANSAH patients who are neurologically intact and without an EVD are likely to have a benign clinical course and may benefit from early ICU de-escalation.

Safety and Feasibility of a “Fast‐Track” Monitoring Protocol for Patients Treated With Intravenous Thrombolytic Therapy

Background Our health care systems continue to face significant strain due to chronically taxed intensive care resources. A subgroup of patients following thrombolytic stroke may not require prolonged intensive monitoring, alleviating some burden. Here, we describe the safety, feasibility, and utility of a Fast‐Track Protocol (FTP) for early deescalation of high‐acuity monitoring. Methods We compared a prospective cohort of patients on the FTP at our stroke centers from April 2020 to February 2022 to a similar retrospective cohort. Those who presented with a National Institutes of Health Stroke Scale &lt;10 and without large‐vessel occlusion or flow‐limiting stenosis, intravenous antihypertensive use, and any hemodynamic or respiratory concerns were eligible. Primary outcomes included early neurologic deterioration, defined as worsening of National Institutes of Health Stroke Scale score of ≥4 points at 24 hours, parenchymal hemorrhage, and symptomatic intracranial hemorrhage. Results Of 574 patients undergoing thrombolysis, 119 (21%) were eligible for the FTP. A total of 100 (88%) were included for analysis. The median±interquartile range hospitalization was 2.0±1.6 days. None of the 4 cases of early neurologic deterioration were due to hemorrhage. No symptomatic intracranial hemorrhages occurred, and no patients on the FTP were transferred back to the intensive care unit. Median±interquartile range 90‐day modified Rankin scale score was 1±1. Conclusion FTP is a safe and feasible strategy to triage intensive care unit patients and decrease unnecessary intensive care unit monitoring. This is important in a postpandemic era as intensive care unit resources continue to fluctuate. Future studies are needed to establish the optimal level of monitoring in patients following thrombolysis.

Early de-escalation of antibiotic therapy in hospitalized cellular therapy adult patients with febrile neutropenia.

Febrile neutropenia (FN) is an oncologic emergency frequently encountered in hematopoietic cell transplant (HCT) and chimeric antigen receptor (CAR) T-cell therapy patients, which requires immediate initiation of broad-spectrum antibiotics. Data regarding antibiotic de-escalation (DE) in neutropenic patients are limited, and guideline recommendations vary. A clinical protocol for antibiotic DE of broad-spectrum agents was implemented if patients were afebrile after 72 hours and had no clinical evidence of infection. The primary endpoint was the difference in the number of antibiotic therapy days between the pre-and post-DE protocol implementation group. Secondary endpoints included rates of subsequent bacteremia during index hospitalization, 30-day mortality, and hospital length of stay. Retrospective chart reviews were conducted to assess outcomes for patients who received allogeneic HCT, autologous HCT, or CAR T-cell therapy under the antibiotic de-escalation protocol (post-DE) compared to those who did not (pre-DE). The pre-DE group underwent HCT/CAR T-cell from February 2018 through September 2018 (n=64), and the post-DE group from February 2019 through September 2019 (n=67). The median duration of antibiotics was significantly lower in the post-DE group (6 days; range 3-60 days) compared to the pre-DE group (8 days; range 3-31 days) (p=0.034). There were no differences in any secondary endpoints. We conclude that antibiotic DE in neutropenic HCT or CAR T-cell therapy patients treated with broad-spectrum antibiotics for at least three days who are afebrile and without documented infection appears to be a safe and effective practice. Adopting it significantly reduces the number of days of antibiotics without compromising patient outcomes.

Efficacy of an antimicrobial stewardship intervention for early adaptation of antibiotic therapy in high-risk neutropenic patients

BackgroundThe 4th European Conference on Infections in Leukemia recommends early adaptation of empirical antibiotic therapy (EAT) for febrile neutropenia in stable patients.ObjectivesTo assess the efficacy of an antimicrobial stewardship (AMS) intervention promoting early de-escalation and discontinuation of EAT in high-risk neutropenic patients.MethodsThis before-after study was conducted in the hematology department of the University Hospital of Nice, France. The AMS intervention included the development of clinical decision support algorithms, a twice-weekly face-to-face review of all antibiotic prescriptions and monthly feedback on the intervention. The primary endpoint was overall antibiotic consumption during hospital stay, expressed as days of therapy (DOT).ResultsA total of 113 admissions were included: 56 during the pre-intervention period and 57 during the intervention period. Induction chemotherapy and conditioning for allogeneic stem cell transplantation were the most frequent reasons for admission. In the intervention period, there was a significant decrease in overall antibiotic consumption (median DOT 20 vs. 28 days, p = 0.006), carbapenem consumption (median DOT 5.5 vs. 9 days, p = 0.017) and anti-resistant Gram-positive agents consumption (median DOT 8 vs. 11.5 days, p = 0.017). We found no statistical difference in the rates of intensive care unit admission (9% in each period) and 30-day mortality (5% vs. 0%, p = 0.243). Compliance with de-escalation and discontinuation strategies was significantly higher in the intervention period (77% vs. 8%, p < 0.001).ConclusionA multifaceted AMS intervention led to high compliance with early de-escalation and discontinuation of EAT and lower overall antibiotic consumption, without negatively affecting clinical outcomes.

Development of machine learning algorithms for scaling-up antibiotic stewardship

BackgroundAntibiotic stewardship programs (ASP) aim to reduce inappropriate use of antibiotics, but their labor-intensive nature impedes their wide adoption. The present study introduces explainable machine learning (ML) models designed to prioritize inpatients who would benefit most from stewardship interventions. MethodsA cohort of inpatients who received systemic antibiotics and were monitored by a multidisciplinary ASP team at a tertiary hospital in the Republic of Korea was assembled. Data encompassing over 130,000 patient-days and comprising more than 160 features from multiple domains, including prescription records, laboratory, microbiology results, and patient conditions was collected.Outcome labels were generated using medication administration history: discontinuation, switching from intravenous to oral medication (IV to PO), and early or late de-escalation. The models were trained using Extreme Gradient Boosting (XGB) and light Gradient Boosting Machine (LGBM), with SHapley Additive exPlanations (SHAP) analysis used to explain the model’s predictions. ResultsThe models demonstrated strong discrimination when evaluated on a hold-out test set(AUROC - IV to PO: 0.81, Early de-escalation: 0.78, Late de-escalation: 0.72, Discontinue: 0.80). The models identified 41%, 16%, 22%, and 17% more cases requiring discontinuation, IV to PO, early and late de-escalation, respectively, compared to the conventional length of therapy strategy, given that the same number of patients were reviewed by the ASP team. The SHAP results explain how each model makes their predictions, highlighting a unique set of important features that are well-aligned with the clinical intuitions of the ASP team. ConclusionsThe models are expected improve the efficiency of ASP activities by prioritizing cases that would benefit from different types of ASP interventions along with detailed explanations.

Association of early antibiotic de-escalation with length of stay in patients with myeloid neoplasms and neutropenic fever.

425 Background: Neutropenic fever is a common complication in patients with myeloid neoplasms. While patients typically receive intravenous (IV) antibiotics until neutrophil recovery, a growing body of literature shows the safety of de-escalation prior to this endpoint. The impact of this early de-escalation on health care utilization remains unclear. Methods: We conducted a retrospective analysis of hospitalized myeloid neoplasm patients at our institution with neutropenic fever, assessing the impact of IV antibiotic de-escalation prior to neutrophil recovery on length of stay (LOS). Manual chart review was performed on this cohort to assess clinical outcomes. Multivariable linear regression was performed, adjusting for age, diagnosis, Charlson Comorbidity Index, intensity of chemotherapy received, positive bacterial culture result, last hospital day with fever, and last hospital day with neutropenia. Results: Patient characteristics are shown in Table 1. Most de-escalation patients (67.7%) were discharged within 72 hours of stopping IV antibiotics. After adjusting for the above variables, early antibiotic de-escalation was associated with lower LOS of 2.7 days (95% confidence interval [CI] 2.0–3.3 days, p &lt; 0.001), an effect that appeared most pronounced in the high very risk chemotherapy group (3.6 day reduction, 95% CI 2.5–4.6 days, p = 0.007). Review of clinical outcomes of de-escalation patients showed 5 potentially preventable recurrent or worsening fever or infectious incidents. Conclusions: Early de-escalation of IV antibiotics was associated with a statistically and clinically significant reduction in LOS, with very few clinical complications. To our knowledge, our study is the first to demonstrate a significant reduction in length of stay, an important hospital quality metric. Further prospective data is needed to confirm this relationship.[Table: see text]

Reducing antimicrobial overuse through targeted therapy for patients with community-acquired pneumonia: a study protocol for a cluster-randomized factorial controlled trial (CARE-CAP)

BackgroundCommunity-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients.MethodsWe will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay.DiscussionOur study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP.Trial registrationClinicalTrials.gov NCT05568654. Registered on October 4, 2022.

Early Antibiotic Deescalation and Discontinuation in Patients with Febrile Neutropenia after Cellular Therapy: A Single-Center Prospective Unblinded Randomized Trial

The optimal duration of empiric antimicrobial therapy of febrile neutropenia in patients after cellular therapy is unclear. Early deescalation has been suggested by some authorities; however, data are lacking for cellular therapy recipients. We performed a randomized controlled study of cellular therapy recipients with febrile neutropenia to evaluate the safety and noninferiority of an early deescalation and discontinuation antibiotic strategy (EDD arm) versus standard broad-spectrum antibiotic treatment until recovery of neutropenia (standard duration arm). The primary outcome was the fraction of antibiotic-free neutropenia days. We randomized 110 patients to the standard duration arm (n=51) or EDD arm (n=59). The fraction of antibiotic-free neutropenia days was higher in the EDD arm compared to the standard duration arm (median, .8 [interquartile range (IQR), .62 to .86] versus .51 [IQR, .17 to .86]; P=.016). This was true for the per-protocol, allogeneic hematopoietic cell transplantation (HCT), autologous HCT, and anti-CD19 chimeric antigen receptor T cell therapy subgroups. Treatment success rate, subsequent fever, death within 30 days, and other common cellular therapy-related toxicities were all similar between the 2 study arms. An EDD antibiotic strategy in patients after cellular therapy was safe and associated with a substantial reduction in broad-spectrum antibiotic utilization without compromising cellular therapy outcomes.

Restrictive fluid management and early fluid de-escalation versus usual care in critically ill patients: A feasibility trial protocol for the REDUCE randomized clinical trial

Background: Fluid therapy is an essential therapeutic intervention for critically ill patients. Both fluid overload and hypovolemia are associated with poor outcomes. However, the fluid strategy in intensive care units is still controversial, and there is no consensus on using the fluid strategy in patients with circulatory shock. Objectives: To compare the efficacy of protocol-based fluid-restrictive management versus standard care in critically ill patients with circulatory shock. Methods: This is a single-center, feasibility-based, randomized, controlled trial in critically ill patients with circulatory shock receiving either fluid resuscitation or vasopressors in two medical ICUs at Siriraj Hospital. Eligible patients will be randomly allocated in a 1:1 ratio and placed in the restrictive fluid strategy (intervention) group or standard care (control) group. The primary outcome is accumulative fluid balance 72 hours after enrollment. Conclusions: This study will evaluate the efficacy and safety of a protocol-based fluid restrictive strategy in critically ill patients who have circulatory shock and are receiving fluid resuscitation or vasopressors.