Phase 1 study of the safety, tolerability, and pharmacokinetics of a synthetic macrocyclic peptide antibiotic (BRII-693) in healthy adult participants.

BRII-693 is a next-generation intravenous (IV)-administered synthetic macrocyclic peptide antibiotic for infections caused by drug-resistant gram-negative pathogens. This single-center, randomized, double-blind, placebo-controlled phase 1 study investigated the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of BRII-693 in 104 healthy participants. In single-dose cohorts, 10-400 mg of BRII-693 was evaluated in eight participants (six active; two placebo) per cohort.

A phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the pharmacokinetics, safety, and tolerability of oral ceftibuten in healthy adult subjects.

This was a phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of oral ceftibuten to describe the pharmacokinetics (PK) of ceftibuten (administered form) and ceftibuten (metabolite), and to describe safety and tolerability at higher than licensed doses. Subjects received single 400, 600, or 800 mg doses of ceftibuten on Days 1 and 4, followed by 7 days of twice-daily dosing from Days 4 to 10. Non-compartmental methods were used to describe parent drug and metabolite PK in plasma and urine.

potency of xeruborbactam in combination with multiple β-lactam antibiotics in comparison with other β-lactam/β-lactamase inhibitor (BLI) combinations against carbapenem-resistant and extended-spectrum β-lactamase-producing .

Recently, several β-lactam (BL)/β-lactamase inhibitor (BLI) combinations have entered clinical testing or have been marketed for use, but limited direct comparative studies of their activity exist. Xeruborbactam (XER, also known as QPX7728), which is undergoing clinical development, is a cyclic boronate BLI with potent inhibitory activity against serine (serine β-lactamase) and metallo-β-lactamases (MBLs). The objectives of this study were (i) to compare the potency and spectrum of β-lactamase inhibition by various BLIs in biochemical assays using purified β-lactamases and in microbiological assays using the panel of laboratory strains expressing diverse serine and metallo-β-lactamases and (ii) to compare the potency of XER in combination with multiple β-lactam antibiotics to that of other BL/BLI combinations in head-to-head testing against recent isolates of carbapenem-resistant (CRE).

Pharmacokinetic-Pharmacodynamic Target Attainment Analyses as Support for Meropenem-Vaborbactam Dosing Regimens and Susceptibility Breakpoints.

Meropenem-vaborbactam is a fixed-dose beta-lactam/beta-lactamase inhibitor with potent and activity against Klebsiella pneumoniae carbapenemase (KPC)-producing . Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were undertaken using population pharmacokinetic models, nonclinical PK-PD targets for efficacy, surveillance data, and simulation to provide support for 2 g meropenem-2 g vaborbactam every 8 h (q8h) administered as a 3-h intravenous (i.v.

The Ultrabroad-Spectrum Beta-Lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-Lactam Antibiotics against Beta-Lactamase-Producing Strains of Resistant .

QPX7728 is a cyclic boronate ultrabroad-spectrum beta-lactamase inhibitor, with potent activity against both serine beta-lactamases and metallo-beta-lactamases. QPX7728 can be delivered systemically by the intravenous (i.v.