The following article analyses the excipients used in the parenteral formulations registered by the U.S. Food and Drug Administration (FDA) in the years 2011 and 2021. It adds real-word data for parenteral excipients in approved products from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) and the Irish Health Products Regulatory Authority (HPRA) in 2021. Maximum daily exposures (MDEs) for all parenteral excipients that had their amount listed either in the Medsafe or HPRA database are presented. Altogether, there were 355 excipients found in the parenteral dosage forms across all markets (US, New Zealand, and Ireland). Only 90 excipients (25.3%) were found in all three markets. In contrast, there were 187 (52.7%) excipients found in only one market. The MDE values of parenteral excipients from New Zealand and Ireland are frequently higher than the values found in the FDA inactive ingredients database (IID), adding important new information when the toxicity of these excipients is considered. There is a heterogenicity between the markets in use of parenteral excipients, with the US market leading in the number of total excipients as well as excipients present only in the US market. Nevertheless, there are several excipients not found in the US market that are registered in other markets. The comprehensive listing of parenteral excipients used worldwide presented in this article enables formulation scientists to quickly reference all potential parenteral excipients that are already proven safe and acceptable when designing a new parenteral formulation. Further, a list of new values for the MDE, often higher than those listed in the IID, provides important information for formulation scientists and toxicologists about the potential toxicity of these excipients.

Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy.
METHODS: We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy. We included studies without restrictions on language or publication year. Eligibility was reviewed independently by two assessors, and data extraction was cross validated. We evaluated bias risk via the Cochrane tool and determined the evidence certainty using GRADE. Meta-analysis was conducted using a random effects model. The protocol of this review was registered on PROSPERO (CRD42023460389).
RESULTS: Thirteen RCTs, involving 1,310 participants were included. We found no difference in mortality (Risk Ratio [RR] 0.54, 95% Confidence Interval [CI] 0.23 to 1.26; P = 0.93), treatment failure (RR 1.0, CI 0.59 to 1.72; P = 0.99), adverse reaction related to antimicrobials (RR 0.89, CI 0.69 to 1.15; P = 0.38), and administration device (RR 0.58, CI 0.17 to 1.98; P = 0.87) between outpatient and inpatient parenteral antimicrobial therapy. The overall body of evidence had a low level of certainty.
CONCLUSIONS: Existing evidence suggests OPAT is a safe and effective alternative to inpatient treatment. Further RCTs are warranted for a thorough comparison of inpatient and outpatient parenteral antimicrobial therapy with a high level of certainty.

There are many factors to consider when selecting a container closure system for parenteral drug products to maintain their quality, efficacy, and safety. One aspect to consider for products stored in glass vials is the glass type. Although the glass vials in which most parenteral products are stored are classified as Type I by the United States Pharmacopoeia, Chapter <660>, not all glass vials that meet the glass performance characteristics of Type I are equivalent. In the study presented here, Type I glass vials from three suppliers of three different Type I glass vials (standard, delamination control, and coated) were investigated to evaluate the impact that each Type I glass vial had on the stability of a drug product under development. To evaluate this impact, a three-phase study was conducted in which the compatibility between the drug product and each vial was assessed through the measurement of the critical quality attributes of the product, extractable and leachable inorganic elements were analyzed for each vial, and finally a stability study under accelerated conditions was conducted for the drug product in the most compatible vial based on the aforementioned experiments. Results from this study demonstrated that there are, in fact, significant differences in glass vials regardless of their classification as Type I. In the study conducted here, delamination control Type I glass vials were found to be superior to both Standard Type I and coated Type I vials for the drug product under investigation.

In the wake of the COVID-19 pandemic, and its negative impact on both acute and elective care and decline in available inpatient resources, there is an imperative to maximize safe and effective alternatives to inpatient hospital care. Properly governed outpatient parenteral antimicrobial therapy (OPAT) services embed the principles of antimicrobial stewardship (AMS) (including use of early oral therapy) and support admission avoidance and early discharge for a growing range of patient groups with complex infections through well-organized multidisciplinary team working. Expansion of OPAT aligns with the UK\'s national strategy to deliver care closer to home and cost-effectively maximize use of inpatient resources. OPAT serves as an exemplar to other ambulatory services and presents opportunities for developing and assuring AMS strategies within the rapidly developing hospital-at-home and virtual ward environments.

Particulate contamination, the unintentional presence of particles in parenteral fluids, is associated with potential risks such as phlebitis and thrombophlebitis. Recent guidelines recommend the use of filter needles when withdrawing parenteral fluid from vials with a rubber stopper. However, the literature is limited and lacks clarity regarding the advantages of filter needles over conventional needles. The aim of this study was to assess the compliance of parenteral fluids regarding particulate contamination after withdrawing fluid using both conventional needles and filter needles, following the guidelines of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP). Visible particles were counted through visual inspection and sub-visible particles were quantified utilizing the light obscuration particle count test. Particle counts for both types of needles were compared to Ph. Eur. and USP standards and differences in particle contamination were assessed using a Mann-Whitney U test. Both types of needles demonstrated compliance with Ph. Eur. and USP standards regarding particulate contamination of visible and sub-visible particles. However, filter needles exhibited a significantly higher particle count for particles with a size of ≥25 µm compared to conventional needles (p = 0.0029). In conclusion, both types of needles demonstrate suitability for aspirating fluid from vials featuring rubber stoppers regarding particulate contamination. Nevertheless, non-filter needles are preferred for withdrawing fluid from vials with a rubber stopper over filter needles due to their lower cost.

Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.

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Outpatient parenteral antimicrobial therapy (OPAT) relies on substantial uncompensated provider time. In this study of a large academic OPAT program, the median amount of unbilled OPAT management time was 27 minutes per week, per OPAT course. These data should inform benchmarks in pursuing novel payment approaches for OPAT.

Outpatient parenteral anti-infective therapy (OPAT) involves the administration of intravenous anti-infectives outside a hospital setting. This shortens the inpatient stay and leads to a reduction in treatment costs, fewer instances of nosocomial infections and enhanced quality of life for the patient.
UNASSIGNED: Die ambulante parenterale antiinfektive Therapie (APAT) bezeichnet die Applikation intravenöser antiinfektiver Substanzen außerhalb des Krankenhauses. Diese Vorgehensweise ermöglicht eine Verkürzung der Krankenhausliegedauer und reduziert so das damit verbundene Risiko nosokomialer Infektionen. Gleichzeitig trägt die APAT dazu bei, die Lebensqualität der Patient:innen zu verbessern. Im vorliegenden Beitrag werden die Grundzüge der APAT beschrieben. Organisation, Planung und konkrete Durchführung werden erläutert.