Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced<i>Staphylococcus aureus</i>mastitis

Badawy, Shymaa A. El; Amer, Aziza M.; Kamel, Gehan M.; Eldeib, Kamal M.; Constable, Peter D.

doi:10.1111/jvp.12790

Cited by 5 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the TAR of over 90% was also attained easily when we removed isolates with MIC over than 16 μg/ml. Thus, the rational dose was consistent with current dosage, but it was much higher than that recommended in Shymaa's study (37.5 mg) (El Badawy et al, 2019). A smaller species (goat) was used in Shymaa's study, which means the milk volume is lower and the concentration in milk for the same dose is higher compared to our study.…”

Section: Discussionsupporting

confidence: 85%

“…Several PK/PD studies of cefquinome have been undertaken. Shymaa studied the PK/ PD relationship of intramammary cefquinome in healthy and experimentally induced Staphylococcus aureus mastitis lactating goats (El Badawy et al, 2019). Yu Y investigated the in vivo PK/PD modeling of cefquinome against E. coli and Staphylococcus aureus mastitis through intramammary administration in lactating mice (Yu et al, 2016(Yu et al, , 2017.…”

Section: Backg Rou N Dmentioning

confidence: 99%

See 1 more Smart Citation

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli

Xiao

Chen

Yan

et al. 2021

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

Cefquinome is the fourth generation of cephalosporin approved solely in animal usage. In order to slow down the resistance development of E. coli to cefquinome, and to protect and maintain the effectiveness of cefquinome, an ex vivo PK/PD modeling of cefquinome against E. coli in cows after intramammary infusion administration was conducted. The epidemiologic cutoff (ECOFF) and pharmacodynamic cutoff (COPD) of cefquinome against E. coli in lactation cows after intramammary infusion administration were recommended. The MICs of cefquinome against 1073 clinical E. coli isolates ranged from 0.015 to >64 μg/ml, and the ECOFF was defined as 0.125 μg/ml. The pharmacokinetic results showed that cefquinome maintained high concentration in milk for a long period with the T1/2β of 10.60 h after intramammary infusion in dairy cows. The drug concentration in skimmed milk was still as high as 0.15 mg/ml after 48 h. Cefquinome displayed bacterial killing effect at 2× MIC with the initial inoculum of 106 cfu/ml in vitro; however, the same effect was attained with a concentration as high as 32× MIC with the initial inoculum of 108 cfu/ml both in artificial medium and in skimmed milk. The initial inoculum is an important factor on time‐killing curve accounting for weakened killing pattern of cefquinome. The AUC0–24 h/MIC index correlated well with ex vivo efficacy. The AUC0–24 h/MIC values for bactericidal effect were 50, 016, and 67,644, respectively, for initial inoculum of 106 and 108 cfu/ml, indicating the bacterial loading or the severity of infection would infect the PK/PD modeling results. The ex vivo PK/PD‐based population dose prediction indicated a target attainment rate (TAR) at the existing daily dose (75 mg/udder) of 84.77% against E. coli. Thus, it was recommended as rational dosage. The COPD of cefquinome against E. coli was determined as 8 μg/ml at the dose of 75 mg/udder. The derived ECOFF, COPD, together with ex vivo PK/PD‐based population dose prediction served as important steps in the establishment of optimum dose regimen and provided a useful interpretative criterion to categorize the antimicrobial susceptibility testing results of cefquinome.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Backg Rou N Dmentioning

confidence: 99%

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli

Xiao

Chen

Yan

et al. 2021

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Under the recommended dose (55 mg/gland/12 h), even severely infected mastitis (10 8 CFU/mL) could be cured, much less the slight infection mastitis (10 6 CFU/mL). It was higher than that recommended in Shymaa's study (37.5 mg) ( 39 ) because in this study the severe infection (8 log 10 CFU/mL) was concerned. In addition, the recommended dose (55 mg/gland/12 h) was lower than the present using dose regimen (75 mg/gland/12 h) without reducing the antibacterial effect.…”

Section: Discussioncontrasting

confidence: 55%

Ex Vivo Pharmacokinetics and Pharmacodynamics Modeling and Optimal Regimens Evaluation of Cefquinome Against Bovine Mastitis Caused by Staphylococcus aureus

et al. 2022

View full text Add to dashboard Cite

Cefquinome, the fourth-generation cephalosporin applied solely for veterinary medicine, is commonly used for bovine mastitis caused by Staphylococcus aureus. The present study aims to establish an optimal dose and provide a PK/PD Cutoff value (COPD) for cefquinome against S. aureus based on ex vivo pharmacokinetics and pharmacodynamics (PK/PD) integration. This study investigated the pharmacokinetics (PK) of cefquinome when administered as three consecutive intramammary (IMM) doses of cefquinome in three healthy dairy cows at 75 mg/gland. Drug concentration was determined by HPLC-MS/MS assay. The ex vivo pharmacodynamics (PD) of cefquinome were evaluated by using a milk sample from a PK experiment. The relationship between the AUC/ MIC of cefquinome and bacterial loading reduction was simulated using a Sigmoid Emax model. The cefquinome concentration in milk attained a maximum level of 1.55 ± 0.21 mg/mL at 1.8 h after the third administration. The mean value of the area under the concentration-time curve (AUC0−24) was 26.12 ± 2.42 mg·h/mL after the third administration. The elimination half-life was 10.6 h. For PD profile, the MICs of cefquinome in milk were 2–4 times higher than those in the broth. In vitro time-killing curve shows that initial bacterial concentration has a huge impact on antibacterial effect on three strains. The antibacterial effect was weakened with the initial bacterial concentration increasing from 106 to 108 CFU/mL. The AUC0−24h/MIC index correlated well with ex vivo efficacy both for the initial inoculum of 106 CFU/mL and 108 CFU/mL (R2 > 0.84). According to the inhibitory sigmoid Emax model analysis, the PK/PD surrogate (AUC0−24/MIC) values were 8,638, 1,397, and 3,851 for bactericidal effect (E = −3) with an initial inoculum of 106 CFU/mL, while the corresponding values were 12,266, 2,295, and 5,337, respectively, with the initial inoculum of 108 CFU/mL. The ex vivo PK/PD based population dose prediction indicated a target attainment rate (TAR) of 90% of 55 mg/gland/12 h. The COPD for cefquinome against S. aureus was 2 μg/mL under the recommended dose of 55 mg/gland/12 h. However, it should be validated in clinical practice in future investigations. These results contribute to the rational use of cefquinome for mastitis treatment in clinical veterinary medicine.

show abstract

“…In general, cephalosporins have low penetration into milk [ 62 , 63 , 64 , 65 , 66 ] with variable pharmacokinetic parameters and slower milk depletion in mastitic animals [ 67 , 68 ]. Cephalexin exhibited a nearly double terminal serum elimination half-life in ewes compared to cattle, in addition to increased concentrations of cephalexin residues [ 69 ].…”

Section: Data Extraction and Presentation (Antibiotic Drug Classes Re...mentioning

confidence: 99%

Antibacterial Drug Residues in Small Ruminant Edible Tissues and Milk: A Literature Review of Commonly Used Medications in Small Ruminants

Richards

Martin

Donnell

et al. 2022

Animals

View full text Add to dashboard Cite

This review provides a summary of extracted data from the published literature that contains drug residue depletion data for edible tissues and milk following treatment of sheep and goats. Out of 20,234 records obtained during the initial search, data from 177 records were included in this review. The data is separated by antibiotic class for ease of comparison between studies. Extracted data includes the active ingredient, dosing information, animal health status, analytical method and limits of detection, tolerance and maximum residue limit information, and time frames relative to residue absence or detection. This information is useful for understanding drug residue depletion profiles following extra-label use and for estimating withdrawal intervals, in order to protect the human food chain.

show abstract

Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally inducedStaphylococcus aureusmastitis

Cited by 5 publications

References 46 publications

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli

Ex Vivo Pharmacokinetics and Pharmacodynamics Modeling and Optimal Regimens Evaluation of Cefquinome Against Bovine Mastitis Caused by Staphylococcus aureus

Antibacterial Drug Residues in Small Ruminant Edible Tissues and Milk: A Literature Review of Commonly Used Medications in Small Ruminants

Contact Info

Product

Resources

About