Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids

Zhang, B.X.; Lu, Xiao-xiong; Gu, Xiaoyan; Li, X.H.; Gu, Mengxiao; Zhang, N.; Shen, Xiu; Ding, Huanzhong

doi:10.1016/j.tvjl.2013.12.015

Cited by 28 publications

(38 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported terminal half life, clearance and Vss were respectively 2.4 ± 0.21 h, 0.11 ± 0.03 L/h.kg, 0.3 ± 0.5 L/kg and were very close to our values. The terminal elimination half-life of cefquinome is similar to values that were observed in piglet (Zhang et al, 2014), ducks (Liguo et al, 2011), rabbit (Hwang et al, 2011), and horses (Winther et al, 2011) in the range of (0.9–2.77 h) following IV administration. The volume of distribution at steady state was low which means that cefquinome was not as widely distributed as previously reported for piglet (Zhang et al, 2014), sheep (Uney et al, 2011), rabbits (Hwang et al, 2011), and horses (Winther et al, 2011) in the range (0.19–0.36 L/kg).…”

Section: Discussionsupporting

confidence: 81%

“…The objective of the approach described here is to clear an organism of a pathogen, which was expected to be present in the central compartment during acute infection. Our model for S. aureus with a MIC of 0.25 μg/mL lead to AUC 24 h /MIC for bacteriostasis and bactericidal action close 30 and 52 h which are higher than those (21 and 35 h, respectively) reported in piglet cage tissue fluid for a strain of E. coli with an MIC of 0.03 μg/mL (Zhang et al, 2014). The PK-PD surrogates have been widely used to provide dosages that aim to ensure clinical cures.…”

Section: Discussionmentioning

confidence: 54%

“…For time-dependent drugs such as cephalosporin, it was rarely reported and as far as we know, only one recent paper investigated in vivo the mutant selection window for cefquinome against E. coli in an in vitro model (Zhang et al, 2014). For S. aureus , the observed in vitro MPC (2 μg/mL) was 8 times higher than the MIC (0.25 μg/mL).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, some strategies have been established for dosage regimens to attain appropriate PK/PD targets in severe infection and to minimize selection of antibiotic resistance (Drusano, 2004; Olofsson and Cars, 2007; Duszyńska, 2012). Recently, one researcher investigated the pharmacokinetics and ex-vivo pharmacodynamics activity of cefquinome by using tissue cage fluid and serum obtained from pigs (Zhang et al, 2014). Efficacy of different dosage regimens was investigated in a Staphylococcus aureus infection in a thigh model of neutropenic mouse (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

et al. 2015

View full text Add to dashboard Cite

Cefquinome is a fourth generation cephalosporin with antimicrobial activity against gram negative and gram positive bacterial species, including Staphylococcus aureus. The aim of our study was to observe the ex-vivo activity of cefquinome against Staphylococcus aureus strains by using bovine serum from intravenously treated cattle. Cefquinome kinetics were measured by liquid chromatography and UV detection. In vitro post antibiotic effects (PAEs) and mutant prevention concentrations were determined with S. aureus strain ATCC 12598. Cefquinome exhibited time-dependent killing and produced in vitro PAEs increasing with concentration and time of exposure. A pharmacokinetic-pharmacodynamic model was established to simulate the efficacy of cefquinome for different dosage regimens. A dosage of 2 mg/kg every 12 h for 3 days was expected to reach a bactericidal activity against S. aureus in case of septicemia.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These data suggest that animal dosage regimens should supply a %ƒT ϾMIC of CEQ for 20 to 40% of the interval for S. suis 2. Based on a previous pharmacokinetic study of CEQ in pigs (37), MIC distribution (38), and the value of %ƒT ϾMIC target indices, a 5,000-subject Monte Carlo simulation was performed using Crystal Ball Professional, version 11.1.2.4, software to predict a reasonable dosage regimen. The probability of target attainment (PTA) of Ͼ100% could be achieved for a static effect and 1-log 10 killing effect for a MIC of Յ0.13 g/ml under the recommended clinical dose of 2 mg/kg/24 h, indicating that the current recommended CEQ dosages are sufficient in treating infectious diseases of pig caused by S. suis 2.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes

Guo

Liao

Wang

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

c Streptococcus suis serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as S. suis. This study evaluated the in vitro and in vivo antimicrobial activities of CEQ against four strains of S. suis serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (10 6 to 10 8 CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (E max ) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%ƒT >MIC ) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (R 2 ‫؍‬ 91% and R 2 ‫؍‬ 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (P ‫؍‬ 0.006) and a 2-fold exposure time (P ‫؍‬ 0.01) were required for a 1-log kill using large inocula of 10 8 CFU/thigh. Streptococcus suis is an important pathogen in the swine industry and causes significant economic losses worldwide. Moreover, it is an emerging zoonotic pathogen causing severe infection in people who have close contact with diseased pigs or pork-derived products (1, 2). To date, 35 serotypes based on S. suis capsular antigens have been described. S. suis serotype 2 is the most virulent and the dominant pathogenic serotype. It has been associated with a variety of severe clinical infections such as meningitis, septicemia, pneumonia, arthritis, and endocarditis in both pigs and humans (3, 4). Significant public health concerns were raised due to large outbreaks of S. suis 2 in humans that occurred in China in 1998 and 2005 that caused high morbidity and mortality (5). Because suitable vaccines were not available, the control of S. suis 2 infections depended almost entirely on the use of antimicrobials. However, the occurrence of high levels of resistance of S. suis to certain antimicrobials (e.g., macrolides, lincosamides, tetracyclines, and sulfonamides) has limited the choice of antimicrobial agents for treatment (6). It has previously been reported that the majority of S. suis strains are susceptible to ␤-lactams (MIC of Յ0.03 g/ml). This suggested that these drugs may be efficacious in the treatment of S. suis 2 infections (7).Cefquinome (CEQ) is a fourth-generation cephalosporin developed solely for veterinary use and has been highly effective against a wide variety of Gram-positive and Gram-negative bacteria (8). CEQ has also been tested and was shown to be effective in animals using a standard thig...

show abstract

Pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation of cefquinome in llamas, following intravenous, intramuscular and subcutaneous administration in serum and tissue cage fluid

Himelfarb

Lorenzutti

Litterio

et al. 2017

Small Ruminant Research

View full text Add to dashboard Cite

Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids

Cited by 28 publications

References 23 publications

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes

Pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation of cefquinome in llamas, following intravenous, intramuscular and subcutaneous administration in serum and tissue cage fluid

Contact Info

Product

Resources

About