Webb, Andrew

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.

ABSTRACT Background Critically ill patients may be overexposed to valproate because altered protein binding leads to a disproportionate free valproate fraction. The Fraser equation was derived and internally validated to estimate critically ill patients' free valproate concentrations, but it requires external validation. Methods Adult intensive care unit (ICU) patients at two academic centers with concurrently measured free and total valproate concentrations were included. Free valproate concentrations were estimated using the Fraser equation which includes total valproate, albumin and BUN concentration, and whether the patient received propofol or aspirin. The primary outcome was Fraser equation performance, assessed using Bland–Altman methods. Comparative performance against estimates from the Doré equation (an alternative predictive equation), therapeutic concordance using a target free valproate range of 5–15 mg/L, and equation improvements were explored. Results Overall, 315 patients and 556 free‐total valproate concentration pairs were included. The mean (±SD) age was 58 (±17) years and 90 (29%) patients were on valproate prior to hospital admission. The Fraser equation estimated free valproate concentrations were correlated with measured concentrations ( r = 0.728) with a negative bias (mean bias −2.77 mg/L, 95% LOA –18.9, 13.4). The Fraser equation increasingly underestimated measured concentrations as measured concentrations increased. 71% of Fraser equation estimates were therapeutically concordant (e.g., estimate and measured both within reference range) compared to 61.9% of Doré estimates ( p = 0.001). Fraser equation modifications led to minor performance improvements but did not overcome worsening underestimation with higher measured free valproate concentrations. Conclusion The Fraser equation was moderately accurate and corresponded with an appropriate interpretation for 71% of free valproate concentrations. Worse underestimation with higher measured free valproate concentrations suggests direct measurement of free valproate concentrations is warranted. While the Fraser equation could complement therapeutic decision making at centers where direct free valproate measurements are unavailable or slow to return, its accuracy is currently insufficient to replace direct measurement.

ABSTRACT 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).

AbstractBackgroundTwitter has emerged as a powerful networking and educational tool within the health care community. The instantaneous and casual nature of Twitter allows for easy access to a near limitless pool of medical professionals and the opportunity to share intra‐ and interprofessional knowledge. Beyond individual development, Twitter has the potential to positively impact pharmacy residency programs in a multitude of ways.ObjectiveThis article serves as a practical guide for pharmacy residency programs to implement and maintain a successful Twitter account.RecommendationsAt the program level, a Twitter account creates an official voice and brand while simultaneously providing detail and perspective beyond what a residency website may offer. Additionally, it allows for dynamic ground‐level engagement with prospective residency candidates, current residents, and preceptors which is mutually beneficial to the program audience. In the age of virtual recruitment, successfully utilizing digital tools to meet candidates where they are is essential for attracting the right candidate for the program. Implementation of a successful social media strategy has potential barriers that include garnering buy‐in from departmental leadership, operationalizing a social media team, and maintaining engagement momentum.ConclusionPharmacy residency programs should consider starting an official Twitter account.

Abstract Background Nontuberculous mycobacteria (NTM) are resistant to numerous antibiotics and lead to significant morbidity and mortality. Omadacycline (OMC) is an aminomethylcycline antibiotic that is Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Furthermore, OMC has shown in vitro activity against NTM. Given that real-world evidence is lacking, our primary objective was to evaluate the clinical success and tolerability of OMC when used for a variety of NTM infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to June 2021. We included all patients ≥ 18 years of age that received OMC of any indication for Mycobacterium spp. The primary outcome was clinical success, defined as a lack of all-cause mortality, lack of persistence or re-emergence of infection during or after therapy, and lack of alteration of OMC. Incidence of adverse effects potentially attributable to OMC and reasons for OMC utilization were also analyzed. Results A total of 31 patients were included from 12 geographically distinct academic health systems (median age: 57 (IQR, 45-63) years; 45% male; 81% Caucasian). The majority of isolated pathogens were Mycobacterium abscessus complex (84%) and of those with subspeciation performed (54%), the majority (86%) were subsp. abscessus. The primary infections were of pulmonary origin (67%) and the median (IQR) duration of OMC therapy was 5.3 (3.2-9.4) months. Most isolates did not have OMC susceptibility conducted (87%), while the majority did for tigecycline (90%). Clinical success was reported in 81% of the population. Most patients were on combination antimicrobial therapy, and 39% of patients reported an adverse effect while on OMC (58% gastrointestinal distress). The majority of patients were prescribed OMC due to ease of administration (61%) and antimicrobial resistance to previous antibiotics (42%). Conclusion OMC may be a potential option for the therapy of NTM infections. Prospective, randomized clinical trials are needed to confirm our preliminary findings. Disclosures Julie V. Philley, MD, Paratek Pharmaceuticals (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

OBJECTIVES: Beta-lactam antibiotics exhibit high interindividual variability in drug concentrations in patients with critical illness which led to an interest in the use of therapeutic drug monitoring to improve effectiveness and safety. To implement therapeutic drug monitoring, it is necessary to define the beta-lactam therapeutic range—in essence, what drug concentration would prompt a clinician to make dose adjustments up or down. This objective of this narrative review was to summarize evidence for the “floor” (for effectiveness) and “ceiling” (for toxicity) for the beta-lactam therapeutic range to be used with individualized therapeutic drug monitoring. DATA SOURCES: Research articles were sourced from PubMed using search term combinations of “pharmacokinetics,” “pharmacodynamics,” “toxicity,” “neurotoxicity,” “therapeutic drug monitoring,” “beta-lactam,” “cefepime,” “meropenem,” “piperacillin/tazobactam,” “ICU,” and “critical illness.” STUDY SELECTION: Articles were selected if they included preclinical, translational, or clinical data on pharmacokinetic and pharmacodynamic thresholds for effectiveness and safety for beta-lactams in critical illness. DATA SYNTHESIS: Experimental data indicate a beta-lactam concentration above the minimum inhibitory concentration of the organism for greater than or equal to 40–60% of the dosing interval is needed, but clinical data indicate that higher concentrations may be preferrable. In the first 48 hours of critical illness, a free beta-lactam concentration at or above the susceptibility breakpoint of the most likely pathogen for 100% of the dosing interval would be reasonable (typically based on Pseudomonas aeruginosa). After 48 hours, the lowest acceptable concentration could be tailored to 1–2× the observed minimum inhibitory concentration of the organism for 100% of the dosing interval (often a more susceptible organism). Neurotoxicity is the primary dose-dependent adverse effect of beta-lactams, but the evidence remains insufficient to link a specific drug concentration to greater risk. CONCLUSIONS: As studies advance the understanding of beta-lactam exposure and response in critically ill patients, it is essential to clearly define the acceptable therapeutic range to guide regimen selection and adjustment.

Abstract Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin (7/12; 58.3%). The median (interquartile range) duration of OMC was 6.2 (4.2–11.0) months. Clinical success occurred in 9/12 (75.0%) patients. Three patients experienced a possible adverse effect while on therapy.

Abstract Background Omadacycline (OMC) is an aminomethylcycline antibiotic in the tetracycline class that has been Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. OMC has been shown to have potent in vitro activity against a broad-spectrum of Gram-positive and Gram-negative organisms, as well as Nontuberculous Mycobacteria (NTM). Due to it’s unique activity and availability as an oral agent, off-label use of OMC has been increasing. We evaluated the real-world effectiveness and safety of OMC for a variety of infections. Methods This was a multicenter, retrospective, observational study that was conducted from January 2020 to June 2020. We included all patients ≥ 18 years of age that received OMC for ≥ 72 hours for any indication and/or pathogen. The primary outcome was clinical success, defined as a lack of 30-day (non-NTM) or 90-day (NTM) mortality or microbiologic recurrence and absence of therapy escalation or alteration. Reasons for OMC utilization and incidence of potential adverse effects attributable to OMC were also analyzed. Results A total of 18 patients were included from six geographically distinct academic health systems (median age: 56 (IQR, 49-60.5) years; 61% male; 72% Caucasian). The majority of OMC use was in NTM (61%; 100% Mycobacterium abscessus) and in Acinetobacter baumannii (22%) for bone/joint (39%) and respiratory tract (33%) infections. OMC was used primarily in the outpatient setting alone (83%) and most isolates did not have OMC susceptibility conducted (89%). Clinical success was reported in 83% of the total population (71% non-NTM and 91% NTM). The majority of patients were prescribed OMC due to antimicrobial resistance to previous antibiotic(s) (61%) and/or due to OMC’s availability as an oral agent (44%). Three patients experienced side effects while on therapy (serum creatinine elevation, AST/ALT increase, and gastrointestinal distress). Conclusion OMC appears to be effective and well-tolerated for a variety of infections caused by various pathogens, including M. abscessus and A. baumannii. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)