Background: Daptomycin is widely used in bone and joint infections (BJIs) caused by Gram-positive cocci. The pharmacokinetics of daptomycin are characterized by relevant variability in terms of drug exposure. Due to these pharmacological properties, the dosing suggested by the Summary of medical Product Characteristics could result in sub-therapeutic or toxic concentrations, especially considering the high doses recommended for BJIs. Therapeutic Drug Monitoring (TDM) of daptomycin helps clinicians in verifying the patient’s exposure, due to the lack of pharmacokinetic/pharmacodynamic (PK/PD) data in this clinical setting. Methods: We retrospectively analyzed 170 daptomycin plasma concentrations of 77 patients with BJIs from July 2022 to December 2023. We focused on the pharmacokinetics of daptomycin to investigate when drug plasma concentrations achieved adequate PK/PD targets. Results: In the first TDM, 7.8% of patients were underexposed according to the estimated area under the curve (eAUC_0–24h < 666 mg·h/L), whereas 35.1% were on target according to both the eAUC and trough plasma concentration (eAUC_0–24h 666 − 939 mg·h/L; C_min < 24.3 mg/L). The patients who were overexposed had trough plasma concentrations > 24.3 mg/L (27.3%) or eAUC_0–24h > 1174 mg·h/L (33.8%). Differences in drug exposure were observed according to weight and sex. Conclusions: Due to the difficult management of this drug’s dosing, analyzing daptomycin plasma concentrations through TDM represents a powerful tool in BJIs.

Carbapenem-resistant Acinetobacter baumannii (A. baumannii; CRAB) isolates represent a serious public health concern. Recently, a novel molecule, the cefiderocol (FDC), has emerged as a promising therapeutic option for CRAB infections. In the present study, we analysed the genomes of five A. baumannii ST2 isolates from four hospitalized patients. All patients were treated with FDC and an ampicillin/sulbactam (AMP/SUL) combination. Whole-genome sequencing of the five CRAB isolates was performed using an Illumina MiSeq instrument. A detailed bioinformatic analysis was carried out to acquire information about genotyping, antimicrobial resistance genes (ARGs), virulence associated genes (VAGs), single nucleotide polymorphisms (SNPs), and the phylogenetic tree of the five CRAB isolates. Among the five CRAB isolates, only three (Ab.2, Ab.3, and Ab.4) exhibited resistance to FDC. The genomes of all isolates were highly similar, and multilocus sequence typing (MLST) analysis indicated they all belong to sequence type 2 (ST2), corresponding to international clone 2. Phylogenetic analysis suggests that isolates Ab.2, Ab.3, and Ab.4 may share a common ancestor or be linked by a possible transmission event. In contrast, isolates Ab.1 and Ab.5 were more divergent from the other three. Nevertheless, all five isolates harboured the same ARGs and VAGs. The OXA-23, OXA-66, and ADC-25 β-lactamases were detected in all strains. The FDC-non-susceptible isolates showed a K235N/H370Y double mutation within PBP3, along with a G370C substitution in PBP1a. The four clinical cases described in this study represent an important example of the efficacy and good practice of FDC plus AMP/SUL combination in the treatment of critical patients suffering from CRAB infections. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

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.

Background: Daptomycin is a once‐daily lipopeptide antibiotic with a narrow therapeutic window. As higher doses (8–12 mg/kg) are increasingly used to treat resistant gram‐positive infections, achieving therapeutic exposure while minimizing toxicity has become critical. Understanding daptomycin therapeutic drug monitoring (TDM) and what sampling strategy may be most precise and feasible are key to guiding appropriate dosing. The primary objective of this study was to ascertain the precision and bias of a mid‐point sample area under the curve over 24‐h (AUC ₂₄ ) determination compared to a peak and trough sample AUC ₂₄ determination using both simple calculation‐based methods and a Bayesian model versus no TDM. Methods: Adult patients receiving daptomycin with at least three steady‐state concentrations (peak, mid‐point, trough) were included in this analysis. A previously published one‐compartment population pharmacokinetic model was applied using Bayesian estimation (Monolix Suite 2024R1). AUC ₂₄ values were estimated using all three concentrations (AUC _ref ), and then re‐estimated using individual samples (peak, mid‐point, or trough) or paired samples (peak + trough). Performance of each strategy was evaluated using regression analysis with the coefficient of determination for precision ( R ² ) and mean bias. Results: The cohort included 210 patients (60% male) with a mean (range) age of 66 (18–91) years, body weight 78 (41–140) kg, and BMI 27 (14–51) kg/m ² . A total of 880 daptomycin concentrations were analyzed in patients receiving a mean (range) daptomycin dose of 9 (5–17) mg/kg. The mean (range) AUC ₂₄ was 869 (385–1692) mg·h/L; only 45.7% of patients achieved the target range of 666 to 939 mg·h/L. A single mid‐point sample had similar correlation to AUC ₂₄ ( R ² = 0.57) as trough‐only ( R ² = 0.55), and greater precision than peak‐only ( R ² = 0.44). Bayesian estimation with two samples (peak + trough) provided the highest accuracy ( R ² = 0.87) and lowest bias. Conclusions: A mid‐interval sampling strategy offers a practical alternative to traditional TDM for daptomycin, enabling more consistent AUC estimation when full sampling is not feasible. A two‐sample Bayesian approach remains the most accurate, supporting broader implementation of individualized daptomycin dosing.