Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals’ experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction of new antimicrobials and novel combinations are exciting developments but also further complicate IE treatment choices. In this review, we provide and evaluate the relevant evidence focused around contemporary debates in IE treatment pharmacotherapy, including beta-lactam choice in MSSA IE, combination therapies (aminoglycosides, ceftaroline), the use of oral antimicrobials, the role of rifamycins, and long-acting lipoglycopeptides.

Introduction: Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. Methods: This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. Results: Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4–16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6–10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8–18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). Conclusion: Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes.

Objective: To evaluate the effects early de-escalation of antipseudomonal β-lactam (APBL) on 90-day CDI risk in Enterobacterales bloodstream infections (BSIs). Design: Retrospective cohort analysis. Setting: An academic medical center in South Carolina. Patients: We included patients aged >18 years with monomicrobial BSIs with Enterobacterales who received APBL between July 1, 2015, and June 30, 2020. Methods: Rates of CDI were compared between patients who received an APBL for >72 hours and <72 hours, followed by comparison between formulary APBLs utilized. Results: In total, 447 patients were included; 292 and 155 patients received APBL for < 72 hours and > 72 hours, respectively. The incidences of CDI for 72 hours were 2.4% and 6.5%, respectively (unadjusted hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.03–7.10; P = .04). This difference was not statistically significant in the adjusted model (HR, 2.66; 95% CI, 0.97–7.31; P = .06). Meropenem was associated with an increased risk of CDI when compared with all other formulary APBLs: 4 (26.7%) of 15 versus 13 (3.0%) of 432 (P < .001). Conclusions: Utilization of an APBL for >72 hours was associated with a statistically significant increase in the incidence of CDI in an unadjusted model and with a numerically higher CDI incidence in the adjusted model. Meropenem was the formulary APBL that carried the highest risk of CDI. The results of this study provide further evidence supporting active antimicrobial stewardship to reduce unnecessary broad-spectrum antibiotics in the effort to alleviate the burden that CDI imposes on the healthcare system.