Evaluation of the post-antibiotic effect for the combination of a β-lactam antibiotic and a β-lactamase inhibitor: ceftazidime-avibactam in neutropenic mouse thigh and lung infections.

The post-antibiotic effect (PAE) of ceftazidime-avibactam was evaluated using models of thigh- and lung-infection with in neutropenic mice. In thigh-infected mice, the PAE was negative (-2.18 to -0.

Pharmacodynamics of fosfomycin against ESBL- and/or carbapenemase-producing Enterobacteriaceae.

Background: The increase in antibiotic resistance in Gram-negative bacteria and the limited therapeutic options due to the shortage of new antibiotics have increased the interest of the 'old' antibiotic fosfomycin in the treatment of infections. However, there are contradictory reports on the pharmacodynamics of and emergence of resistance to fosfomycin.

Methods: Time-kill assays were performed with 11 ESBL-positive and 3 ESBL-negative strains, exposing the bacteria to 2-fold static concentrations from 0.

Pharmacodynamics of nitrofurantoin at different pH levels against pathogens involved in urinary tract infections.

Background: Urinary tract infections are among the most common human infections. Due to the progressive increase in ESBL-producing bacteria and the unavailability of new antibiotics, re-evaluation of 'old' antibiotics is needed. However, the pharmacodynamics of nitrofurantoin under variable pH conditions are poorly understood.

Pharmacodynamics of Cefepime Combined with Tazobactam against Clinically Relevant Enterobacteriaceae in a Neutropenic Mouse Thigh Model.

The lack of new antibiotics has prompted investigation of the combination of two existing agents-cefepime, a broad-spectrum cephalosporin, and tazobactam-to broaden their efficacy against extended-spectrum beta-lactamase (ESBL)-producing We determined the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the combination in a murine neutropenic thigh model in order to establish its exposure-response relationships (ERRs). The PK of cefepime were determined for five doses; that of tazobactam was determined in earlier studies (Melchers et al., Antimicrob Agents Chemother 59:3373-3376, 2015, https://doi.

Pharmacodynamics of Ceftazidime and Avibactam in Neutropenic Mice with Thigh or Lung Infection.

Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combinations of ceftazidime-avibactam for treating infections with ceftazidime-resistant Pseudomonas aeruginosa, pharmacodynamic responses were explored in murine neutropenic thigh and lung infection models. Exposure-response relationships for ceftazidime monotherapy were determined first.

Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice.

Ceftazidime and the β-lactamase inhibitor avibactam constitute a new, potentially highly active combination in the battle against extended-spectrum-β-lactamase (ESBL)-producing bacteria. To determine possible clinical use, it is important to know the pharmacokinetic profiles of the compounds related to each other in plasma and the different compartments of infection in experimentally infected animals and in humans. We used a neutropenic murine thigh infection model and lung infection model to study pharmacokinetics in plasma and epithelial lining fluid (ELF).