Background/Objectives: Elastomeric infusion pumps have emerged as a transformative tool in outpatient parenteral antimicrobial therapy (OPAT), enabling continuous intravenous administration outside hospital settings, enhancing patient autonomy, reducing healthcare costs, and playing a role in antimicrobial stewardship. This aim of this review is to update current evidence on antibiotic stability in elastomeric infusion pumps, analyzing environmental factors, clinical efficacy, and practical challenges associated with OPAT implementation. Methods: A narrative review was conducted using PubMed and the Cochrane Library, focusing on studies published between 2022 and 2025. Included studies assessed antibiotic stability in elastomeric pumps under real-world and laboratory conditions, examining factors such as temperature sensitivity, light exposure, and material interactions. Results: Findings indicate considerable variability in antibiotic stability, with some agents maintaining prolonged efficacy while others degrade rapidly under certain conditions. Antibiotics with greater stability are better suited for OPAT, whereas those prone to degradation present challenges for continuous infusion. Clinical studies report favorable treatment outcomes, including high cure rates and manageable adverse event profiles. However, discrepancies between laboratory-controlled conditions and real-world settings highlight the necessity for more comprehensive stability evaluations to ensure optimal antibiotic selection and administration in OPAT programs. Conclusions: Optimizing antibiotic formulations, standardizing stability protocols, and advancing elastomeric pump technologies are essential for enhancing OPAT effectiveness. Future research should focus on real-world simulation studies and refining device materials to expand the range of stable antibiotics, ensuring safer and more efficient outpatient antimicrobial therapy.

(1) Background: Granulicatella adiacens is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment strategy, and partially due to higher rates of complications, such as heart failure, peripheral septic embolism, and peri-valvular abscess, as well as a higher rate of valve replacement. Depending on the affected valve (native valve endocarditisNVE, or prosthetic valve endocarditisPVE), the American Heart Association (AHA) 2015 treatment guidelines (GLs) suggest penicillin G, ampicillin, or ceftriaxone plus gentamicin (2 weeks for NVE and up to 6 weeks for PVE), while vancomycin alone may be a reasonable alternative in patients who are intolerant of β-lactam therapy. The European Society of Cardiology (ESC) 2023 GLs recommend treating NVE with penicillin G, ceftriaxone, or vancomycin for 6 weeks, suggesting combined with an aminoglycoside (AG) for at least the first 2 weeks only for PVE; likewise, the same recommendations for IE due to Enterococcus faecalis. (2) Methods: Starting from the case of a 51-year-old man with G. adiacens aortic bio-prosthesis IE who was successfully treated with aortic valve replacement combined with double beta-lactams, an AG-sparing regimen, we performed microbiology tests in order to validate this potential treatment change. (3) Results: As for E. faecalis IE, we found that the combination of ampicillin plus cephalosporines (like ceftriaxone or ceftobiprole) showed a synergistic effect in vitro, probably due to wider binding to penicillin-binding proteins (PBPs), thus contributing to enhanced bacterial killing and good clinical outcome, as well as avoiding the risk of nephrotoxicity due to AG association therapy. (4) Conclusions: Further studies are required to confirm this hypothesis, but double beta-lactams and an adequate sourcecontrol could be a choice in treating G. adiacens IE.