Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin

Abstract

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded I8-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.

Use of Accuracy Profile Procedure to Validate a Real-Time PCR Method to Quantify Bacteria in Feces

“…We can conclude that cefquinome had no effect on the Bacteroides-Prevotella group, as was shown by Limbert et al (28), who found that 11 of the 14 tested strains were resistant to cefquinome at an in vitro concentration higher than 100 µg/mL (28).…”

“…The high in vivo activity of cefquinome against the genus Bifidobacterium was supported by the absence of detection during the treatment period (28). Bifidobacteria were detected before and after the treatment, while during cefquinome administration from Day 1 to Day 3, Bifidobacterium levels dropped below the LOD (5 log 10 CFU/g).…”

Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Staphylococcus aureus Infection

“…Today, S. aureus is recognized as the most commonly implicated organism (22,23). Cefquinome possesses a broad antibacterial spectrum (against, e.g., S. aureus, including MRSA) and favorable pharmacokinetics; thus, it merits further investigation into its chemotherapeutic properties (7). The use of antimicrobial PK-PD analyses to identify the pharmacodynamic activity of antimicrobial agents through the integration of the PK properties, in vitro potency (MIC), and outcome is one approach that has proven helpful for the design of effective dosing regimens in humans and animals, as well as in the development of appropriate in vitro susceptibility breakpoints (15,24,25).…”

“…Cefquinome (formerly HR 111V) is a fourth-generation cephalosporin developed solely for veterinary use. It displays antimicrobial activities in vitro and in vivo against a broad spectrum of Gram-positive and Gram-negative bacterial species, including methicillin-resistant and methicillin-susceptible S. aureus, and it is considered to be highly stable against ␤-lactamases encoded by chromosomes and genes on plasmids (7)(8)(9).…”

Critical parameters for the stability of cefquinome sulfate in aqueous solutions and solid phase

“…A significant enhancement of activity and an extension of the antibacterial spectrum were achieved by the introduction of a methoxyimino-aminothiazolyl moiety into the acyl side chain of the cephalosporin, which made it resistant to inactivation by b-lactamases [6][7][8][9][10][11]. The quaternary quinoline group at position 3 in the cefem ring and the resulting zwitterionic structure facilitate the rapid penetration of cefquinome across the biological membranes of animals and bacteria, ensuring its fast bactericidal action after injection.…”