Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Evaluation of Short Versus Long Courses of Antibiotics in Critically Ill Patients With Gram-Negative Bloodstream Infections.

BACKGROUND: Short courses of antibiotics (7-10 days) are effective for uncomplicated gram-negative bloodstream infections (GN-BSI). However, prior studies have been limited to small cohorts of critically ill patients. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of short courses of therapy compared with longer courses in patients admitted to the intensive care unit (ICU) with GN-BSI. METHODS: Propensity-matched, retrospective cohort study of critically ill patients with GN-BSI. The primary outcome was a composite of 30-day mortality or 60-day relapse. Secondary endpoints were components of the composite, 30-day relapse, cure with or without adverse drug events (ADE), and ADEs. Regression analysis was performed to identify factors predictive of the composite outcome. RESULTS: 225 patients were included in the propensity analysis, 145 in the long cohort and 80 in the short cohort. The primary outcome occurred in 3.8% of patients in the short group and 9.0% of patients in the long group (P = 0.24). There was no difference in 30-day mortality (3.8% vs 5.5%, P = 0.79), 60-day relapse (0% vs 3.4%, P = 0.23), or 30-day readmission (20% vs 22.8%, P = 0.76). ADEs were more common in the long group (47.2% vs 34.1%, OR 1.7, 95% CI 1.04-2.9), primarily attributable to diarrhea. CONCLUSION AND RELEVANCE: In critically ill patients with GN-BSI, there were no efficacy outcome differences in patients treated with a short course of antibiotics compared with longer. However, patients in the short group were less likely to experience ADE. These findings suggest that short courses of antibiotics are effective for GN-BSI in critically ill patients.

Performance of Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening for Ruling Out MRSA Pneumonia in Hospitalized, Immunocompromised Patients.

Background: Recent literature demonstrates support for using methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (NaPCR) screening as an antimicrobial stewardship tool aiding early de-escalation of anti-MRSA antimicrobials. However, immunocompromised patients have been underrepresented in previous studies despite increased risk of morbidity and mortality from multidrug-resistant organisms (MDRO). Objective: The purpose of this study was to determine the negative predictive value (NPV) of the MRSA NaPCR in hospitalized, immunocompromised adult patients with suspected pneumonia. Methods: A single-center, retrospective, observational review was conducted of hospitalized, immunocompromised adult patients that had an MRSA NaPCR obtained between March 1, 2020 and January 10, 2021. For inclusion, bacterial cultures must have been collected within 2 weeks after MRSA NaPCR. The primary outcome was the NPV of MRSA NaPCR in hospitalized, immunocompromised patients with suspected pneumonia. Secondary outcomes include NPV in other infections. Results: Between March 1, 2020 and January 10, 2021, 59 patients with 78 unique cultures, including 28 respiratory cultures, were included in the study. The NPV of the MRSA NaPCR for pneumonia was 91.7%. The NPV for bloodstream infections was 100% and for urinary tract infections was 100%, but interpretation of these results should be cautioned due to the small sample sizes. Conclusion: The NPV of MRSA NaPCR in pneumonia remains high in this study. The MRSA NaPCR has utility as a de-escalation tool in hospitalized, immunocompromised adult patients, but larger studies are warranted to evaluate all immunocompromised patient populations.

Evaluation of Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Prescribing Habits in Patients with a Positive MRSA Nasal Swab in the Absence of Positive Cultures.

Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal swabs are guideline-recommended de-escalation tools in certain patients with pneumonia. Prior studies have demonstrated reduced anti-MRSA therapy with negative results, but the impact on durations of therapy has been poorly elucidated in patients with positive PCRs. The objective of this review was to evaluate anti-MRSA treatment durations in patients with a positive MRSA PCR in the absence of MRSA growth on culture. This was a single-center, retrospective observational study evaluating 52 hospitalized, adult patients receiving anti-MRSA therapy with positive MRSA PCRs. The overall median duration of anti-MRSA therapy was five days, including a median of four days after PCR results. This was consistent among intensive care unit (ICU) and non-ICU patient populations and in patients with suspected community-acquired pneumonia (CAP). Among patients with hospital-acquired pneumonia (HAP), the median duration of anti-MRSA therapy was seven days, with a median of six days after PCR results. Overall, patients received a median duration of anti-MRSA therapy that would constitute a full treatment course for many respiratory infections, which indicates that providers may equate a positive MRSA nasal PCR with positive culture growth and highlights the need for education on the interpretation of positive tests.

Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort.

BACKGROUND: The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. METHODS: This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. RESULTS: One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001). CONCLUSIONS: Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.