Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers.

Background: Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.

In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol.

Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms.

Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions.

Background: Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited.

Linezolid brain penetration in neurointensive care patients.

Background: Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown.

Objectives: To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients.

Plasma and intraperitoneal pharmacokinetics of ceftazidime/avibactam in peritoneal dialysis patients.

Objectives: Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD.

Individualized antimicrobial dose optimization: a systematic review and meta-analysis of randomized controlled trials.

Background: Therapeutic drug monitoring and Model-informed precision dosing allow dose individualization to increase drug effectivity and reduce toxicity.

Objectives: To evaluate the available evidence on the clinical efficacy of individualized antimicrobial dosing optimization.

Methods: Data sources: PubMed, Embase, Web of Science, and Cochrane Library databases from database inception to 11 November 2022.

Comparison of ultrafiltration and microdialysis for ceftriaxone protein-binding determination.

Background: High protein binding (PB) of antibiotics has an impact on their antimicrobial activity. It has been questioned whether in vitro PB determination can capture the dynamic and concentration-dependent PB of highly bound antibiotics.

Objectives: This clinical study compared in vitro ultrafiltration (UF) and in vivo IV microdialysis (MD) methods to determine ceftriaxone PB.

Relationship between Pharmacokinetic/Pharmacodynamic Target Attainment and Microbiological Outcome in Critically Ill COVID-19 Patients with Documented Gram-Negative Superinfections Treated with TDM-Guided Continuous-Infusion Meropenem.

Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram-negative superinfections. Methods: Patients receiving CI meropenem for documented Gram-negative infections at the COVID ICU of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and undergoing therapeutic drug monitoring from January 2021 to February 2022 were retrospectively assessed. Average steady-state meropenem concentrations (Css) were calculated and the Css/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy.

Biomarkers Predicting Tissue Pharmacokinetics of Antimicrobials in Sepsis: A Review.

The pathophysiology of sepsis alters drug pharmacokinetics, resulting in inadequate drug exposure and target-site concentration. Suboptimal exposure leads to treatment failure and the development of antimicrobial resistance. Therefore, we seek to optimize antimicrobial therapy in sepsis by selecting the right drug and the correct dosage.

Meropenem concentrations in brain tissue of neurointensive care patients exceed CSF levels.

Background: Inadequate antibiotic exposure in cerebral infections might have detrimental effects on clinical outcome. Commonly, antibiotic concentrations within the CSF were used to estimate cerebral target levels. However, the actual pharmacological active unbound drug concentration beyond the blood-brain barrier is unknown.