Susceptibility breakpoint for cefquinome against Escherichia coli and Staphylococcus aureus from pigs

Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications.In this study,we established the wild-type cut-off(CO_(WT))and pharmacokinetic/pharmacodynamic cut-off(CO_(PD))of cefquinome against Escherichia coli and Staphylococcus aureus.A total of 210 E.coli and 160 S.aureus isolates were collected from pigs in Guangdong Province between 2014 and 2018.The minimum inhibitory concentrations(MICs)were determined using a microdilution broth method.MIC_(50)and MIC_(90)were 0.06 and 0.25μg m L^(–1)for E.coli and 0.5 and 1μg m L^(–1)for S.aureus,respectively.Statistical analysis and the ECOFFinder Program showed that the CO_(WT)for cefquinome against E.coli and S.aureus were0.125 and 2μg m L^(–1),respectively.The resistance rates were 11.9%for E.coli and 6.25%for S.aureus.Based on a5000-subject Monte Carlo simulation,the CO_(PD)value for cefquinome against E.coil and S.aureus was 0.25μg m L^(–1)under the recommended dose(2 mg kg^(–1),twice a day for 3 days),confirming that infections caused by strains with MIC≤0.25μg m L^(–1)could be effectively treated.Following adjustment of the dosing regimen to 4.5 mg kg^(–1),effective treatment(>90)was achieved for S.aureus infections with MIC_(90)1μg m L^(–1).This susceptibility breakpoint determination is significant for resistant surveillance and cefquinome dosage guidance against E.coli and S.aureus in pigs.

Preparation and Characterization of Lung-targeting Cefquinome-loaded PLGA Microspheres

We developed poly lactic-co-glycolic acid（PLGA） microspheres loaded with cefquinome and tested their effectiveness in a mouse model. The microspheres were prepared by optimizing several key parameters such as PLGA molecular weight, drug/polymer ratio, internal water volume and ethyl acetate. Drug loading efficiency, stability, in vitro release and tissue distribution in mouse were evaluated. The average particle size of the microspheres was 27.84 μm. The drug loading efficiency was 64.57%. The in vitro release of cefquinome from microspheres after 4 h was about 40% compared with over 90% for the drug alone. The concentration of cefquinome in lung reached 25 μg/g 0.25 h after injection, and kept at 10 μg/g 4 h after injection. However, the concentration of cefquinome was very low in other organs even 0.25 h after injection. In conclusion, Cefquinome-loaded PLGA microspheres are compatible as an effective lung-targeting drug delivery system and have a good sustained release efficacy.

Pharmacokinetics and Residues of Cefquinome in Milk of Lactating Chinese Dairy Cows After Intramammary Administration

The purpose of the study was to investigate the pharmacokinetics of cefquinome in plasma and milk samples of lactating Chinese Holstein following a single intramammary administration into one quarter at the dose of 75 mg. Residue depletion of cefquinome in milk administrated at one quarter following three consecutive infusions at the same dose were also carried out. Cefquinome concentrations in plasma and milk were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method. A non-compartmental analysis was used to obtain the pharmacokinetic parameters of cefquinome. Following the single treatment, cefquinome wasn’t detected in any of the plasma samples. The concentration of cefquinome in milk reached peaked values （Cmax） of （599.00±322.00） μg mL-1 at 2 h after administration （Tmax）, elimination half-life （t1/2λz） was （4.63±0.26） h, area under the concentration-time curve （AUC0-∞） was （4 890.19±1 906.98） μg mL-1 h, and mean residence time （MRT） was （6.03±2.27） h. In residue depletion study, cefquinome concentrations in 5 out of 6 milk samples at 72 h were lower than the maximum residue limit ifxed by the European regulatory agency （20μg kg-1 for cefquinome） and cefquinome still could be detected in milk of treated quarters at 120 h post-treatment. The maximum concentration （Cmax） of cefquinome in milk from treated quarters was （486.50±262.92） μg mL-1 and arrived at 6 h after administration （Tmax）, elimination half-life （t1/2λz） was （6.30±0.76） h, area under the concentration-time curve （AUC0-∞） was （44 747.79±11 434.43） μg mL-1 h, and mean residence time （MRT） was （10.09±1.40） h. This study showed that cefquinome has the feature of poor penetration into blood and was eliminated quickly from milk in lactating cows after intramammary administration.

The solubility of cefquinome sulfate in pure and mixed solvents

Solid-liquid equilibrium data of cefquinome sulfate is important to develop industrial crystallization processes for cefquinome sulfate. The solubilities of cefquinome sulfate in five pure solvents （methanol, ethanol, ethylene glycol, acetic acid and water） from 277.15 to 305.15 K and in a binary acetone-water solvent from 278.15 to 293.15 K were measured at atmospheric pressure. The pure-solvent solubility data was correlated to the modified Apelblat and Van＇t Hoff equations whereas the mixed-solvent system data was correlated to the modified Apelblat, Van＇t Hoff, CNIBS/R-K and Jouy- ban-Acree models. It was found that the solubilities of cefquinome sulfate in all tested solvents decreased with the increasing of temperature. In addition, the thermodynamic properties of the dissolution processes, including standard Gibbs free energy, enthalpy and entropy changes, were calculated using the Van＇t Hoff equation. It was found that the dissolution of cefquinome sulfate is exothermic.

硫酸头孢喹肟的质谱研究

Cefquinome was studied by ESI and EI mass spectrometry,and its structure was proved from mass spectrometry. The results indicated that ESI positive ion of cefquinome included[M+H]+529,395.5,323.6,166.6.the main fragmentations of EI MS involved m/z 528,395,239,225,33,132,105,91,77,44,and so on.The structure segment accorded with its cracking.