Pharmacokinetic/pharma-codynamic study of pralurbactam (FL058) combined with meropenem in a neutropenic murine thigh infection model.

Introduction: Pralurbactam (FL058) is a novel β-lactamase inhibitor with good inhibitory activity on class A, C, and D β-lactamases. This study aimed to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) relationship of pralurbactam/meropenem in a neutropenic murine thigh infection model.

Methods: After 2-h infection, neutropenic mice was treated with meropenem every 2 h alone or in combination with pralurbactam at different dosing frequencies for 24 h, and the colony count in the thighs was determined before and after treatment.

Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia.

Purpose: Lefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against and via PK/PD analysis.

Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistant .

Carbapenem-resistant (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B, and colistin/sulbactam combination therapy.

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019.

pharmacokinetics/pharmacodynamics of FL058 (a novel beta-lactamase inhibitor) combined with meropenem against carbapenemase-producing Enterobacterales.

FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an infection model. By simulating human concentration-time profiles in the model, meropenem combined with FL058 when administered 1 g/0.

A combination of genomics and transcriptomics provides insights into the distribution and differential mRNA expression of type VI secretion system in clinical .

Unlabelled: The type VI secretion system (T6SS) serves as a crucial molecular weapon in interbacterial competition and significantly influences the adaptability of bacteria in their ecological niche. However, the distribution and function of T6SS in clinical , a common opportunistic nosocomial pathogen, have not been fully elucidated. Here, we conducted a genomic analysis of 65 clinical isolates obtained from patients with varying infections.

pharmacodynamics of nemonoxacin and other antimicrobial agents against .

This study first reported the effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant (MRMP) and macrolide susceptible (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with .

Pharmacokinetic, Pharmacokinetic/Pharmacodynamic, and Safety Investigations of Lefamulin in Healthy Chinese Subjects.

This study aimed to explore the pharmacokinetics (PK) and safety of oral (PO) and intravenous (IV) lefamulin in healthy Chinese subjects and to evaluate the efficacy of the intravenous administration regimen using pharmacokinetic/pharmacodynamic (PK/PD) analysis. This study was a randomized, open-label, single- and multiple-dose, intravenous and oral administration study. PK parameters were calculated, and the probability of target attainment (PTA) and the cumulative fraction of response (CFR) after IV administration of lefamulin 150 mg 1 h q12 h were analyzed with Monte Carlo simulations.

Pharmacokinetics and Pharmacodynamics of a Novel Vancomycin Derivative LYSC98 in a Murine Thigh Infection Model Against .

Introduction: LYSC98 is a novel vancomycin derivative used for gram-positive bacterial infections. Here we compared the antibacterial activity of LYSC98 with vancomycin and linezolid in vitro and in vivo. Besides, we also reported the pharmacokinetic/pharmacodynamic (PK/PD) index and efficacy-target values of LYSC98.

Highly selective electrocatalytic reduction of nitrate to nitrogen in a chloride ion-free system by promoting kinetic mass transfer of intermediate products in a novel Pd-Cu adsorption confined cathode.

The mass transfer on the catalyst surface has a great influence on the selectivity of electrocatalytic nitrate reduction to nitrogen. In this study, a Pd-Cu adsorption confined nickel foam cathode is designed in the absence of both proton exchange membranes and chloride ions. The repulsion of the cathode enables intermediate products such as nitrite to accumulate in the confined region, resulting in an increase in the possibility of a second-order reaction to form nitrogen.

Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in .

is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of have not been fully elucidated.

Proteomic Response Revealed Signaling Pathways Involving in the Mechanism of Polymyxin B-Induced Melanogenesis.

Polymyxin B is a last-line antibiotic for extensively resistant Gram-negative bacterial infection. Skin hyperpigmentation is a serious side effect induced by polymyxin B that severely compromises the psychological health and compliance of patients. The literature lacks mechanistic studies that explain how hyperpigmentation occurs, and this substantially hinders the development of intervention strategies and improved compliance.

Pharmacokinetics and pharmacodynamics of peptide antibiotics.

Antimicrobial resistance is a major global health challenge. As few new efficacious antibiotics will become available in the near future, peptide antibiotics continue to be major therapeutic options for treating infections caused by multidrug-resistant pathogens. Rational use of antibiotics requires optimisation of the pharmacokinetics and pharmacodynamics for the treatment of different types of infections.

Polymyxin B Combined with Minocycline: A Potentially Effective Combination against bla-harboring CRAB in In Vitro PK/PD Model.

Polymyxin-based combination therapy is commonly used to treat carbapenem-resistant (CRAB) infections. In the present study, the bactericidal effect of polymyxin B and minocycline combination was tested in three CRAB strains containing bla by the checkerboard assay and in vitro dynamic pharmacokinetics/pharmacodynamics (PK/PD) model. The combination showed synergistic or partial synergistic effect (fractional inhibitory concentration index ≤0.

Pharmacokinetic/Pharmacodynamic Based Breakpoints of Polymyxin B for Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Pathogens.

The latest PK/PD findings have demonstrated negligible efficacy of intravenous polymyxins against pulmonary infections. We investigated pharmacokinetic/pharmacodynamic (PK/PD)-based breakpoints of polymyxin B for bloodstream infections and the rationality of the recent withdrawal of polymyxin susceptibility breakpoints by the CLSI. Polymyxin B pharmacokinetic data were obtained from a phase I clinical trial in healthy Chinese subjects and population pharmacokinetic parameters were employed to determine the exposure of polymyxin B at steady state.

Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China.

Pharmacometrics is an emerging science that interprets drug, disease, and trial information in a mathematical fashion to inform and facilitate efficient drug development and/or regulatory decisions. Pharmacometrics study is increasingly adopted in the regulatory review of new antimicrobial agents. We summarized the 31 antimicrobial agents approved by the US Food and Drug Administration (FDA) and the 26 antimicrobial agents approved by European Medicines Agency (EMA) from January 2001 to May 2019.

Epidemiological and genomic characteristics of Acinetobacter baumannii from different infection sites using comparative genomics.

Background: Acinetobacter baumannii is a common nosocomial pathogen that poses a huge threat to global health. Owing to the severity of A. baumannii infections, it became necessary to investigate the epidemiological characteristics of A.

Pharmacokinetics and Pharmacodynamics of Nemonoxacin in a Neutropenic Murine Lung Infection Model Against .

Nemonoxacin, a novel nonfluorinated quinolone for the treatment of community-acquired pneumonia. We reported the pharmacokinetic/pharmacodynamic (PK/PD) targets and PK/PD breakpoints of nemonoxacin against using a neutropenic murine lung infection model. Single-dose PK analysis after subcutaneous administration of nemonoxacin at doses from 2.

Pharmacokinetics of Levornidazole Tablet in Healthy Chinese Subjects and Proposed Dosing Regimen Based on Pharmacokinetic/Pharmacodynamic Analysis.

Introduction: Levornidazole is a novel nitroimidazole antimicrobial agent active against anaerobes. We aimed to investigate the pharmacokinetic (PK) profile of levornidazole after single and multiple oral doses of levornidazole tablets in healthy Chinese subjects and propose the dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis.

Methods: A single-center, randomized, double-blind, placebo-controlled study was conducted with a single ascending dose (250, 500, 1000, and 1500 mg) and multiple doses of 500 mg levornidazole q12h for 7 days.

Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.

Purposes: To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin.

Methods: Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted in 18 healthy Chinese subjects. Both CMS formulas met the requirements of European Pharmacopoeia 9.

Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects.

Objectives: Polymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.

Enhanced bacterial killing with colistin/sulbactam combination against carbapenem-resistant Acinetobacter baumannii.

Aims: Polymyxin-based combination therapy is often used to treat carbapenem-resistant Acinetobacter baumannii (A. baumannii) infections. Although sulbactam is intrinsically active against A.

Therapeutic drug monitoring of polymyxin B by LC-MS/MS in plasma and urine.

A robust and rapid method for therapeutic drug monitoring (TDM) is urgently needed for polymyxin B, which is a last-line antibiotic for multidrug-resistant gram-negative bacteria infection. A 3-min run of LC-MS/MS method was established to determine the main components of polymyxin B (polymyxin B1 and B2) in human plasma or urine. Solid-phase extraction was employed to eliminate the matrix effect from complicated samples from patients.

Dose Optimization of Colistin Combinations against Carbapenem-Resistant Acinetobacter baumannii from Patients with Hospital-Acquired Pneumonia in China by Using an Pharmacokinetic/Pharmacodynamic Model.

Colistin-based combination therapy has become an important strategy to combat the carbapenem-resistant (CRAB). However, the optimal dosage regimen selection for the combination with maximum efficacy is challenging. Checkerboard assay was employed to evaluate the synergy of colistin in combination with meropenem, rifampin, fosfomycin, and minocycline against nine carbapenem-resistant isolates (MIC of meropenem [MIC], ≥32 mg/liter) isolated from Chinese hospital-acquired pneumonia (HAP) patients.