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.

Cefiderocol: early clinical experience for multi-drug resistant gram-negative infections.

Multi-drug resistant gram-negative bacteria present a significant global health threat. Cefiderocol (CFDC), a siderophore cephalosporin, has shown potential in combating this threat, but with the currently available data, its role in therapy remains poorly defined. This multi-center, retrospective cohort study evaluated the real-world application of CFDC across six U.S. medical centers from January 2018 to May 2023. Patients aged ≥18 years and who had received ≥72 hours of CFDC were included. The primary outcome was a composite of clinical success: survival at 30 days, absence of symptomatic microbiologic recurrence at 30 days following CFDC treatment initiation, and resolution of signs and symptoms. Secondary outcomes included time to CFDC therapy and on-treatment non-susceptibility to CFDC. A total of 112 patients were included, with median (interquartile range [IQR]) APACHE II scores of 15 (19-18). Clinical success was observed in 68.8% of patients, with a mortality rate of 16.1% and comparable success rates across patients infected with carbapenem-resistant gram-negative infections. The most common isolated organisms were Pseudomonas aeruginosa (61/112, 54.5%, of which 55/61 were carbapenem-resistant) and carbapenem-resistant Acinetobacter baumannii (32/112, 28.6%). Median (IQR) time to CFDC therapy was 77 (14-141) hours. Two patients experienced a non-anaphylactic rash as an adverse drug reaction. On-treatment non-susceptibility to CFDC was found in six patients, notably due to P. aeruginosa and A. baumannii.IMPORTANCECFDC was safe and clinically effective as a monotherapy or in combination in treating a variety of carbapenem-resistant gram-negative infections. Further prospective studies are warranted to confirm these findings.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC ß-lactamase Production.

Background: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum ß-lactamase (ESBL) concerns. Methods: This was a retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion ß-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). Conclusions: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive ß-lactam therapy.

Impact of ambulatory pharmacist on hospital visits in older adults with epilepsy: A case-control study.

OBJECTIVE: Older adults have the highest prevalence of epilepsy of any age group. Care in this group is complex because of comorbidities, polypharmacy, and cognitive impairment. We aimed to assess the impact of an ambulatory pharmacist in decreasing hospital visits in this group. METHODS: We performed a case-control study at a tertiary care center. The study group was seen in a multi-disciplinary older adult epilepsy clinic with the services of an ambulatory pharmacist to help with medication reconciliation, assessment, and adherence. The control clinic also cared for older adults with epilepsy but lacked a pharmacist. The occurrence and factors related to hospital visits were compared three months post-clinic visit. Demographic data were reported using descriptive statistics. A multinomial regression analysis was conducted to assess how well hospital visits could be predicted by pharmacist presence and other relevant variables. RESULTS: Over 19 months, 58 and 74 patients were seen in the study and control groups, respectively. 26.6% and 18.4% of study and control group clinic visits were associated with a hospital visit, respectively (nonsignificant difference). The study group had significantly more patients with cognitive impairment (53.4% vs. 16.2%; p < 0.001), a higher burden of comorbidities as measured by Charlson comorbidity index (CCI) (mean 3.5 vs. 2.9; p = 0.02), and a greater number of patients with >1 seizure per month (17.2% vs. 6.8%) as compared to the control group. Hospital visits unrelated to epilepsy were associated with a higher CCI. Hospital visits related to epilepsy were associated with >1/month seizure frequency (>3 times risk). CONCLUSIONS: This study demonstrates the multifactorial complexity of older adults with epilepsy. While the presence of a pharmacist resulted in similar hospital visits as the control group, the study group had a much more complex patient population. More studies are required to assess the best use of a pharmacist in older adults with epilepsy outpatient care.

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure.

The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

Implementation of an older adult epilepsy clinic utilizing pharmacist services.

BACKGROUND: Antiseizure medications are commonly associated with adverse effects including behavioral and cognitive issues, drug interactions, idiosyncratic reactions, and long-term complications, which can lead to non-adherence. At the same time, there are limited reports describing multidisciplinary models of epilepsy care that include pharmacists. OBJECTIVE: To describe the pharmacist services in an epilepsy clinic for older adults and document the patient care delivered using this design. PRACTICE DESCRIPTION: A subspecialty older adult epilepsy clinic, embedded within a neurology clinic, in an urban academic medical center. PRACTICE INNOVATION: Integration of pharmacy services to document medication history, provide medication reconciliation, identify medication-related problems, and make interventions. EVALUATION METHODS: Data were retrospectively evaluated for the patients seen by the pharmacist and epilepsy team between July 2019 and January 2021. Data were summarized with descriptive statistics. RESULTS: Fifty-eight patients with a total of 94 encounters (70.7% of all specialty clinic visits) were seen collaboratively by the physician and the pharmacist. The majority of patients were African American (87.9%), aged 63.7 ± 8.2 years, and more frequently male (58.6%), and a high proportion had some baseline memory loss or diagnosis of dementia (53.4%). Medication reconciliation occurred in 94 (100%) encounters. More than half the encounters required reconciliation to the existing medication list by adding medication (55.3 % of encounters) or deleting mediations (53.2% of encounters). Presence of adverse effects was the most common medication-related problem identified (23.4%). Resolutions to the medication-related problems were also reported. CONCLUSION: The population of older adults with epilepsy is expected to increase in prevalence. Pharmacists are able to impact medication-related problems in a vulnerable, high-risk patient population. The multidisciplinary model we describe here can be used as a template to provide care in ambulatory care practices involving other neurology specialties with a high proportion of older adult patients.

Child development and genre preference: research for educational game design.

As the movement to capitalize on unique affordances of video games for learning continues to grow, relatively little research in that area has examined how formal features, such as genre and game mechanics, draw and hold children's attention. This study examines which genres children prefer and the reasons why children prefer those genres by reporting on a video game uses and gratifications survey of children of various ages (n=685). Results show distinct patterns of game use and preference tied to typical child developmental ecology at each age, indicating that genre preference varies by age and developmental context. Implications for game research and educational gaming are provided.