Bhattarai, Nirjan

Abstract Background Cardiac valve tissue obtained during the surgical management of infective endocarditis (IE) and sent for culture may influence postoperative antibiotic therapy. We sought to identify clinical and microbiologic risk factors associated with positive valve cultures (PVC) and IE relapses in a cohort of patients undergoing surgical management. Methods This is a retrospective, multi-center study of patients with surgical management during the acute (<42 days) course of IE-directed antibiotic therapy. The rate of PVC, IE relapse, and mortality were collected. Univariate and multivariable logistic regressions were performed to identify risk factors associated with PVC. Results Of 113 patients included, 36 (31.9%) had PVC. Univariate and multivariable analyses showed preoperative antibiotic duration and pathogens were associated with PVC. Median (IQR) days of preoperative antibiotics were 6.5 (4.0-11.0) for patients with PVC compared to 13.0 (8.0-21.0) for those with negative valve cultures (NVC). In a multivariable model, preoperative antibiotic administration decreased the risk of PVC (OR 0.85 per day, CI 0.77-0.91). Enterococcal IE increased the risk of PVC compared to streptococcal IE (OR 4.16, CI 1.07-17.48). Of note, 33 (63.2%) patients with NVC received a median (IQR) of 8 (5, 18.5) days of intravenous antibiotics per patient. Only one IE relapse was identified and occurred in a patient with NVC. Conclusions Both preoperative antibiotic duration and causative pathogen were associated with PVC. IE relapses were rare and unrelated to PVC. There may be an opportunity to shorten postoperative antibiotic durations following surgical management in patients with IE.

Abstract Posaconazole delayed-release (DR) tablets are labelled as ‘do not crush’ medications. Despite this designation, emerging research demonstrates successful attainment of therapeutic serum concentrations, suggesting that they may be pharmacokinetically superior to the immediate-release (IR) suspension when given via enteric feeding tube (EFT). While crushed posaconazole DR tablets may be better suited than the IR suspension to attain therapeutic serum concentrations, several practical factors must be considered, including lack of dose equivalency between crushed DR tablets for EFT administration and DR tablets swallowed whole and the risk of EFT occlusion. This article summarizes the current evidence on posaconazole serum concentrations with crushed DR tablets administered via EFT, explores risks of this practice and provides mitigation strategies for application in the clinical setting, including proposed dosing and administration practices.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behavior and results in sub satisfactory concentrations. Limited evidence suggests that the posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum concentration drawn ≥5 days after posaconazole initiation. The primary outcome was the attainment of therapeutic (≥700ng/mL for prophylaxis, ≥1,000ng/mL for treatment) serum concentration within 30 days. Secondary outcomes included time to therapeutic serum concentration, adverse drug effects, and frequency of clogged EFT. Multivariable cox proportional hazards regression was used to assess the relationship between posaconazole formulation and attainment of therapeutic concentrations while adjusting for confounding variables. Results Of the included patients, 100 received DR tablets and 48 received IR suspension. There were no significant differences in baseline characteristics or severity of illness. Among DR tablet and IR suspension recipients, 59% and 23% achieved therapeutic concentrations, respectively (p < 0.001). After adjusting for age, sex, BMI, drug interactions, posaconazole indication, malabsorptive gastrointestinal conditions, IR suspension was significantly less likely than crushed DR tablets to achieve therapeutic posaconazole concentrations within 30-days (HR 0.37, 95% CI 0.20-0.71; p < 0.003). The crushed DR tablet group required less total daily posaconazole to achieve therapeutic concentrations (400 vs 600 mg/day, p = 0.003). Clogged EFTs were more frequent in the crushed DR tablet group (27% vs 10%, p = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalemia. Conclusion Administration of crushed posaconazole DR tablets via EFT is more likely to attain therapeutic concentrations compared to IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation. Disclosures Patrick M. Wieruszewski, PharmD, FCCM, Wolters Kluwer/UpToDate: Advisor/Consultant

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.