Tyler J. Stone

A recent study of Mero vs. P/T for the treatment of BSIs caused by ceftriaxone-resistant Enterobacterales, including ESBL-producing organisms, revealed discouraging outcomes for patients (pts) receiving P/T. The purpose of this study is to evaluate clinical outcomes in pts treated with P/T versus Mero for BSIs caused by ESBL-producing E. coli or K. pneumoniae. This is a single health-system, retrospective, observational study. Adult inpatients with blood cultures positive for ESBL-producing E. coli or K. pneumoniae during 2016-2020 were identified by a report from an automated broth microdilution system. Pts with an isolate susceptible to both P/T and Mero who received either P/T or Mero within 24 hours of culture collection and for a duration of least 48 hours were included. Pts who had neutropenia, expired or transitioned to comfort care within 48 hours of study drug initiation, did not have source control by day 5, had a polymicrobial infection, or had a concurrent infection caused by another gram-negative organism were excluded. Pts were screened for eligibility and then randomly selected until a target of 25 pts meeting study criteria in the Mero and the P/T groups were included. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included length of hospital stay, clinical and microbiological resolution by day 5, and time to clinical and microbiological resolution. Primary and Secondary Outcomes Boxplot A. Length of Stay, B. Time to Clinical Resolution, C. Time to Microbiological Resolution In this real-world study of pts with ESBL-producing BSIs that were predominantly from a urinary source, pts treated with P/T and Mero had similar outcomes. These results demonstrate the need for additional randomized, controlled trials, in a variety of settings to further assess outcomes in this pt population. Tyler J. Stone, PharmD, ViiV Healthcare: Employee

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions. Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP. Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3. Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients. Design: Single-center, preintervention and postintervention retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Adult ICU patients. Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January–March 2021, preintervention period) or after (January–March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared. Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27). Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship.

Objective:To determine whether a multifaceted initiative resulted in maintained reduction in inappropriate treatment of asymptomatic pyuria (ASP) or bacteriuria (ASB) in the emergency department (ED).Design:Single-center, retrospective study.Methods:Beginning in December 2015, a series of interventions were implemented to decrease the inappropriate treatment of ASP or ASB in the ED. Patients discharged from the ED from August to October 2015 (preintervention period), from December 2016 to February 2017 (postintervention period 1), and from November 2019 to January 2020 (postintervention period 2) were included if they had pyuria and/or bacteriuria without urinary symptoms. The primary outcome was the proportion of patients prescribed antibiotics within 72 hours of discharge from the ED. The secondary outcome was the number of patients returning to the ED with symptomatic UTI within 30 days of discharge.Results:We detected a significant decrease in the proportion of patients with ASP or ASB who were inappropriately treated when comparing the preintervention group and post-intervention group 1 (100% vs 32.4%; P < .001). This reduced frequency of inappropriate treatment was noted 3 years after the intervention, with 28% of patients receiving treatment for ASP or ASB in postintervention group 2. (P was not significant fin the comparison with postintervention group 1.) Among the 3 groups analyzed, we detected no difference in the numbers of patients returning to the ED with a symptomatic UTI within 30 days of ED discharge regardless of whether patients received antibiotics.Conclusions:A multifaceted intervention resulted in a significant decrease in inappropriate use of antibiotics for ASP and/or ASB that was maintained 3 years after implementation.

(1) Background: Dalbavancin is a long-acting lipoglycopeptide antibiotic approved for skin and soft-tissue infections. Post-marketing experience suggests dalbavancin is being used for off-label indications that normally require long-term intravenous (IV) antibiotics; however, data assessing this off-label usage are limited. The purpose of this study was to evaluate the real-world efficacy, safety, and financial impact of off-label dalbavancin use. (2) Methods: This is a retrospective, observational study conducted within a 4-hospital health system. Adult patients who received dalbavancin from January 2018 to January 2021 for an off-label indication were included. The primary outcome was clinical success at 90 days. Secondary outcomes included safety (nephrotoxicity and hepatotoxicity). A pharmacoeconomic analysis was performed by comparing the cost of dalbavancin to the anticipated cost of patient stay if standard IV therapy was given. (3) Results: Forty-eight patients met study criteria. Indications included osteomyelitis (54%), endocarditis (23%), bacteremia (15%), and prosthetic joint infection (8%). The predominant organism was S. aureus (60%), with 42% caused by methicillin-resistant S. aureus. Overall, 41 (85%) patients achieved clinical success at 90 days, including 85% with osteomyelitis, 82% with endocarditis, and 86% with bacteremia. There were no instances of nephrotoxicity or hepatotoxicity. Estimated cost avoidance per patient was USD 5313 and USD 1683 if traditional IV therapy would have been completed in the hospital and skilled nursing facility, respectively. (4) Conclusion: Dalbavancin was associated with a relatively high success rate for the treatment of off-label indications and may be a cost-effective alternative to traditional IV antibiotic therapy.