Skip to content

Advertisement

You're viewing the new version of our site. Please leave us feedback.

Learn more

BMC Veterinary Research

Open Access

Pharmacokinetics, bioavailability and dose assessment of Cefquinome against Escherichia coli in black swans (Cygnus atratus)

BMC Veterinary ResearchBMC series – open, inclusive and trusted201713:226

https://doi.org/10.1186/s12917-017-1148-7

Received: 5 April 2017

Accepted: 24 July 2017

Published: 28 July 2017

Abstract

Background

The objective of this study is to investigate pharmacokinetics and dose regimens of cefquinome in black swans following intravenous (IV) and intramuscular (IM) administration at a single dose of 2 mg/kg. The MICs of cefquinome against 49 Escherichia coli isolates from black swans were determined. Monte Carlo simulation was applied to conduct the dose regimen assessment and optimization of cefquinome against E. coli in black swans, and a pharmacokinetic/pharmacodynamic (PK/PD) cutoff was established for E. coli isolates obtained in this study.

Results

The PK parameters of T1/2α (0.31 h), T1/2β (1.69 h) and ClB (0.13 L/kg·h) indicated a rapid distribution and elimination of cefquinome in black swans after IV administration. After IM injection, the corresponding PK parameters of T1/2Ka, T1/2Ke, Tmax, Cmax, and F were 0.12 h, 1.62 h, 0.39 h, 5.71 μg/mL and 74.2%, respectively. The MICs of cefquinome against black swans E. coli ranged from 0.03 to 8 μg/mL, with MIC50 and MIC90 of 0.06 and 0.5 μg/mL, respectively. The PK/PD cutoff of cefquinome against E. coli was determined to be 0.2 μg/mL. Monte Carlo simulation showed that the nominal dose regimen (2 mg/kg/24 h) could not achieve a satisfactory probability of target attainment (PTA) for %TMIC ≥ 50%, indicating a risk of treatment failure and the development of potential drug resistance.

Conclusions

The current daily dosage of cefquinome when divided into 12-h interval (1 mg/kg/12 h) may be effective for the treatment of E. coli infections with an MIC ≤0.5 μg/mL.

Keywords

CefquinomeBlack swansPharmacokineticsMonte Carlo analysis

Background

The black swan (Cygnus atratus) is a large black-feathered waterbird which breeds mainly in New Zealand, Australia and adjacent coastal islands with nomadic migration patterns dependent on climatic conditions. As a popular ornamental bird, black swans have been introduced into numerous countries and have formed stable populations in zoological gardens [1]. In general, clinical bacterial infections caused by Enterobacteriaceae are common in waterfowl [2]. Additionally, Escherichia coli, Salmonella spp. and Campylobacter spp. infections can have serious detrimental on waterfowl populations and pose a potential threat to human public health as well. A recent study has reported the emergence of carbapenem and colistin-resistant E.coli isolates co-carrying bla NDM-5 and mcr-1 genes in the fowls [3], indicating the possible spread and prevalence of such resistant strains through the food chain and migration of wild birds.

Cefquinome is the 4th generation cephalosporin antibiotic developed solely for veterinary use and has been approved for the treatment of many diseases including respiratory tract disease, foot rot in cattle, calf septicemia, metritis-mastitis-agalactia syndrome in sows, foal septicemia and respiratory diseases in horses [4]. Cefquinome is routinely used at a single dose of 2 mg/kg BW once-daily [5]. The advantages of cefquinome include broad-spectrum antimicrobial activity, highly stable against β-lactamases, enhanced potency and the ability to penetrate easily into Gram-negative bacterium [6]. Previous pharmacokinetic studies of cefquinome have been conducted in various species including pigs, cattle, beagle dogs, wild boars and ducks [711]. However, no relavant study regarding administration of cefquinome in wild animals was reported, and most previous studies were focused on the characteristics of drug disposition without regard to the appropriate dose regimen assessment for therapeutic use of cefquinome. Here we report, to the best of our knowledge, for the first time cefquinome PK properties and dose regimens assessment in wild birds.

In the present study, we present the PK profile and bioavailability of cefquinome in black swans. The MICs of cefquinome against 49 E. coli isolates from black swans were also determined. In addition, Monte Carlo analysis was performed to derive the corresponding daily dose regimens required to achieve the specific activity for various MIC breakpoints based on the determined PK parameters in black swans, the MIC distribution and the reported PD targets [12]. These results may provide fundamental data for the assessment of clinical efficacy of cefquinome and suggestions for a more rational dose regimen in black swans expected of having E. coli infections.

Methods

Animals and experimental design

Twelve healthy black swans weighting 5.14 ± 0.79 kg were divided equally into two groups. Each group randomly included three males and three females. Swans in each group received cefquinome (cefquinome sulfate injection, 40 mg/mL, Qilu Animal Health Products Co., Ltd., Jinan, China) at a single dose of 2 mg/kg/24 h BW by IV (brachial vein) or IM (chest muscle) injection. The black swans used in this study were kindly provided by the Lv-Yuan Rare Bird Farm (Shangdong, China). All birds were raised in accordance with the National Standards for Laboratory Animals of China (GB 14925–2010), allowed ad libitum access to water and antibacterial-free feedstuffs. The animal experimental protocol was approved by the Committee on the Ethics of animals of South China Sea Fisheries Research Institute and the Institutional Animal Care and Use Committee of Lv-Yuan Rare Bird Farm.

Sample collection and analysis

Blood (0.5 mL) was collected from the contralateral brachial vein with heparin sodium before and at 0.083, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h following IV or IM administration. Plasma samples were then immediately isolated by centrifugation at 4000 rpm for 10 min and stored at −80 °C until further analysis.

A 0.2 mL aliquot of plasma sample was transferred into a capped centrifuge tube, and then mixed with 0.2 mL of acetonitrile. After vortexing (30 s) and centrifuging (12,000 rpm, 10 min), the supernatant was filtered through a 0.22 μm nylon syringe filter and collected into a sample vial for concentration determination. The plasma cefquinome concentrations were determined using a modified high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method as our previously reported [9] (details are given in Additional file 1). The calibration standards in the linear range of 0.01–0.5 μg/mL were produced by working solutions spiked in blank plasma after extraction. All samples that had concentrations above 0.5 μg/mL were diluted proportionally with the control plasma prior to extraction with acetonitrile. The limit of detection (LOD) and quantification (LOQ) for cefquinome in plasma were set according to signal-to-noise (S/N) ratio of 3:1 and 10:1, respectively. The analytical method was validated by assessing extraction efficiency and inter- and intra-day reproducibility at drug concentrations of 0.01, 0.1 and 0.5 μg/mL.

Pharmacokinetic analysis

Pharmacokinetic parameters of cefquinome were estimated by a compartmental method using WinNonlin software (version 6.1, Pharsight, St. Louis, MO, USA). The best-fitting model required to describe cefquinome time-concentration curves for each swan was determined by application of the weighed residual sums of square and Akaike Information Criterion (AIC) methods [13]. The time-concentration of IV route was best fitted in WinNonlin program using a two-compartment model as presented in Model 7: Concentration (T) = Ae-α∙T + Be-β∙T. The IM route was best fitted in WinNonlin program using a one-compartment model with the first-order absorption as presented in Model 3: \( \mathrm{Concentration}\ \left(\mathrm{T}\right)=\frac{\mathrm{Dose}\kern0.75em \cdot \kern0.5em Ka}{{\mathrm{V}}_{\mathrm{d}}\ \left(Ka\hbox{-} Ke\right)}\ {\mathrm{e}}^{-Ke\cdot \mathrm{T}}\hbox{-} {e}^{-Ka\cdot \mathrm{T}} \). For IV dosing, the distribution and elimination half-lives were estimated as T1/2α = 0.693/α and T1/2β = 0.693/β, respectively. The half-lives of the first-order absorption and elimination after IM injection were correspondingly calculated as T1/2Ka = 0.693/Ka and T1/2Ke = 0.693/Ke. The other PK parameters, peak plasma concentration (Cmax), the time to Cmax (Tmax), the apparent steady-state volume of distribution (Vss), total area under time-concentration curve (AUC) and total body clearance (ClB) were also calculated in WinNonlin software. The bioavailability (F%) was calculated according to the standard equations as follows [14]: \( \mathrm{F}=\kern0.75em \frac{AUC_{IM}}{AUC_{IV}}\times 100\% \). All PK parameters were presented as mean ± SD values.

MIC determination

A total of 49 E. coli strains were obtained from more than 300 faecal swabs of black swans breeded in five different separated populations between 2014 and 2015. The MICs of cefquinome for these E. coli isolates were determined using the standard CLSI microdilution method [15]. The MICs for 50% and 90% of the isolates (MIC50 and MIC90, respectively) were calculated accordingly.

Monte Carlo analysis and dose assessment

For β-lactam antibiotics acting by the time-dependent killing mechanisms, it is commonly recommended that the duration of time that drug levels exceed the MIC (%TMIC) should be at least 50% and possibly more than 80% of the dosing interval to ensure an appropriate bactericidal effect [12]. To further assess the recommended dose regimens of cefquinome in black swans against E. coli, a 10,000-subject Monte Carlo analysis was conducted using the Crystal Ball Professional software (version 7.2.2; Oracle Corporation), based on the current PK parameters, MIC distribution and the PD targets (%TMIC > 50 or 80%).

The %TMIC values after IM injection was calculated using the following equation: \( \mathrm{Concentration}\kern0.75em \left(\mathrm{t}\right)\kern0.5em =\kern0.5em \frac{\mathrm{Dose}\kern0.75em \cdot \kern0.5em Ka\kern0.75em \cdot \mathrm{F}}{{\mathrm{V}}_{\mathrm{d}}\ \left(Ka\hbox{-} Kel\right)}\ {\mathrm{e}}^{\hbox{-} Ke\cdot \mathrm{t}}\hbox{-} {\mathrm{e}}^{\hbox{-} Ka\cdot \mathrm{t}} \), where concentration is the MIC, Vd is the apparent volume of distribution, F is bioavailability, Ka is constant of absorption rate and Ke is constant of elimination rate for IM administration. All PK parameters were assumed to be normally distributed in the form of mean and standard deviation (Table 1). In order to obtain a unimodal distribution, the two isolates with a MIC of 8 μg/mL were consequently removed, and the log2-transformed MIC distribution of the other 47 isolates was submitted to the non-linear least squares regression and standard goodness-of-fit test. The probability of attaining the %TMIC targets at the specific MICs was accordingly calculated. The PK/PD cutoff (COPD) is defined as the MIC, at which the PTA for %TMIC target (50%) was equal to 90% under the current clinical recommended dose (2 mg/kg/24 h). For calculation of daily dose regimens, the MIC was defined as a single value ranging from 0.03 to 8 μg/mL. Scenarios were simulated separately for a single IM injection of cefquinome from 0 to 265 mg/kg with 24-h or 12-h intervals. The precise recipes of cefquinome required to achieve the specific activity (%TMIC > 50 or 80%) against E. coli isolate at each MIC in black swans were also estimated based on PK data, Monte Carlo analysis and the equation mentioned above.
Table 1

Mean ± SD values of the pharmacokinetic parameters of cefquinome in black swans after IV and IM administration at a dose of 2 mg/kg BW

Parameter

Unit

IV

IM

Ka

1/h

5.64 ± 3.07

A

μg/mL

10.7 ± 4.97

α

1/h

2.27 ± 0.23

Kel

1/h

0.43 ± 0.03

B

μg/mL

4.20 ± 1.91

β

1/h

0.42 ± 0.09

Vss

L/kg

0.32 ± 0.17

T1/2Ka

h

0.12 ± 0.04

T1/2α

h

0.31 ± 0.03

T1/2Ke

h

1.62 ± 0.11

T1/2β

h

1.69 ± 0.85

Tmax

h

0.39 ± 0.19

Cmax

μg/mL

5.71 ± 1.43

AUC

μg·h/mL

16.5 ± 4.92

12.17 ± 4.32

ClB

L/kg·h

0.13 ± 0.04

F

%

74.2 ± 26.3

A, zero-time intercept of the distribution slope in the compartment model; B, zero-time inter of decline in plasma concentration of drug; α, distribution rate constant; β, elimination constant; Ke, constant of elimination rate; Ka, constant of absorption rate; T1/2Kel, elimination half-life; T1/2α, the distribution half-life; T1/2β, the half-life of elimination; T1/2Ka, absorption half-life; Vss, the apparent steady-state volume of distribution; ClB, total body clearance; AUC, total area under the concentration–time curve from zero to infinity; Tmax, time to Cmax from time zero; Cmax, peak plasma concentration; F, bioavailability

Results

Cefquinome concentration assay in swan plasma

The matrix-matched calibration curve was linear between 0.01 and 0.5 μg/mL, with a coefficient of determination (R2) of 0.998. The LOQ and LOD were 0.01 and 0.005 μg/mL, respectively. Mean extraction recoveries from the five replicate assays were 88.9 ± 7.96%, 95.2 ± 7.20% and 98.3 ± 7.97% at spiked drug concentrations of 0.01, 0.1, and 0.5 μg/mL, respectively. The intraday coefficients of variation for replicate control samples (n = 5) within these concentration ranges varied from 1.52 to 5.69%, and the interday coefficients of variation ranged from 5.96 to 7.18%.

Pharmacokinetics of cefquinome in plasma

No adverse effect or intolerance was observed during the entire experiment. The plasma time-concentration profiles are plotted in Fig. 1, and the corresponding PK parameters are summarized in Table 1. Cefquinome exhibited a biphasic decline and showed the best fit to a two-compartmental open model after IV dosing in black swans. The distribution half-life (T1/2α) and elimination half-life (T1/2β) were 0.31 ± 0.03 h and 1.69 ± 0.85 h, respectively. After IM injection, the drug time-concentration data was best described by a one-compartment model with first-order absorption. Cefquinome was absorbed rapidly with an absorption half-life (T1/2Ka) of 0.12 h. The peak concentration (Cmax; 5.71 μg/mL) was achieved at 0.39 h, and the bioavailability was 74.2 ± 26.3% after IM injection. No drug was detected at 24 h after cefquinome administration.
Fig. 1

Semi-logarithmic plot of plasma concentration-time profiles of cefquinome after IV and IM administration at a single dose of 2 mg/kg BW. Values are mean ± SD (n = 6)

MIC distribution

As shown in the primitive cefquinome MIC distribution in Fig. 2a, the MICs for cefquinome against 49 E. coli strains isolated from black swans were in the range of 0.03 to 8 μg/mL. The MIC50 and MIC90 were determined to be 0.063 and 0.5 μg/mL, respectively (Additional file 2: Table S1). The distribution percentage at each MIC (0.03, 0.06, 0.13, 0.25, 0.5, 1, 2 and 8 μg/mL) was 26.5%, 42.9%, 14.3%, 6.1%, 2.0%, 2.0%, 2.0% and 4.1%, respectively. In the fitted log2-transformed MIC distribution of the 47 isolates, the best fit for the unimodal population was found (R 2  = 0.85) when presumed MIC distribution was defined as being between 0.03 and 2.0 μg/mL.
Fig. 2

The MIC distribution of cefquinome against E. coli isolates from black swans. a Primary MIC distribution of 49 E. coli isolates; (b) Fitted MIC distribution of the estimated 47 E. coli isolates after the goodness-of-fit tests and nonlinear least-squares regression. The lines indicate fitted theoretical normal distribution values

Monte Carlo analysis and dose assessment

The PTA values of cefquinome administered at single dose of 2 mg/kg/24 h against E. coli at each MIC were presented in Fig. 3. When MIC of E. coli was below 0.2 μg/mL, the PTA for achieving %TMIC > 50% was as high as 90.2%. Therefore, the PK/PD cutoff of cefquinome against 49 E. coli isolates obtained in our study was 0.2 μg/mL. In addition, the calculated daily dosages of cefquinome required to achieve the specific activity (%TMIC > 50% or 80%) against E. coli isolates with different MICs in black swans were summarized in Table 2. A simulated dose regimen (1.86 mg/kg/24 h) would be only therapeutically effective against E. coli with MIC ≤0.125 μg/mL in black swans. However, the similar daily total dose (1.94 mg/kg) may achieve a successful therapy for E. coli with a MIC of ≤0.5 μg/mL after splitting the dose into 12-h intervals (0.97 mg/kg/12 h). Similarly, as shown in Fig. 4, for the used E. coli MIC distribution in the present study, a PTA of 11.2% for %TMIC ≥ 80% was acquired when cefquinome administered at 2 mg/kg once-daily, while 91.9% could be achieved if the same dose given at 12-h intervals (1 mg/kg/12 h).
Fig. 3

The probability of target attainment (PTA) of cefquinome treated with the current clinical dose regimen (2 mg/kg/24 h) against E. coli at each MIC value

Table 2

Calculated total daily dose of cefquinome required to achieve the specific activity (%TMIC > 50% or 80%) against E. coli isolates from black swans with diverse MIC values

MIC (μg/mL) for E. coli isolates

Total daily dose (mg/kg) of cefquinome required to achieve

%TMIC > 50%

%TMIC > 80%

24-h interval

12-h intervals

24-h interval

12-h intervals

0.031

0.45

0.14

3.88

0.38

0.063

0.89

0.24

7.95

0.72

0.125

1.86

0.48

16.4

1.68

0.25

3.25

0.98

33.7

2.96

0.5

7.38

1.94

67.3

6.54

1

14.6

3.86

132.7

12.9

2

29.7

7.72

264.2

27.4

8

115.1

31.2

106.6

Fig. 4

The probability distribution of the calculated %TMIC for cefquinome using a 10,000-subject Monte Carlo analysis based on the measured PK parameters obtained following IM injection at 2 mg/kg BW with 24-h (a and b) and 12-h (c and d) dosing interval in black swans and E. coli MIC distribution in this study. The areas of blue columns represent the probability of target attainment (PTA) for %TMIC ≥ 50 or 80%

Discussion

This study was the first of its kind to investigate PK of cefquinome applied in wild birds. The elimination half-life (T1/2β) of cefquinome after IV administration was 1.69 h, which was similar to those values reported in chickens (1.29 h) and ducks (1.57 h), indicating a relatively short drug persistence in black swans [11, 16]. However, an evidently shorter elimination half-life was observed in beagle dogs (0.98 h) or sheep (0.78 h) [9, 17]. Similarly, a more rapid absorption (T1/2Ka) of cefquinome after IM injection were acquired in black swans (0.12 h), chickens (0.07 h) and ducks (0.12 h) compared with in mammals such as piglets (0.41 h), sheep (0.31 h) and camels (4.35 h) [11, 1720]. This PK property represented a shorter duration for the drug to reach systemic circulation and to more rapidly establish of effective drug concentration in birds.

The diffusion of cefquinome in the body tissues of different animal species is very small. In this study, barely 0.32 L ⁄kg of Vss was obtained in black swans similar to 0.25 L/kg in piglets and 0.19 L/kg in pigs [21, 22]. According to the CVMP report, an attenuated distribution of cefquinome to intracellular spaces was due to low fat solubility and that it acts as an organic acid with a low pKa of 2.51 or 2.91 [5]. In addition, total body clearance (ClB) in black swans was determined to be 0.13 ± 0.04 L/kg·h in this study, which is similar to 0.18 L/kg in rabbits or 0.12 L/kg in horse but lower than the corresponding value of 0.26 L/kg in piglets [18, 23, 24].

As an animal-specific cephalosporin, cefquinome has been widely employed in veterinary medicine due to excellent antimicrobial activity. Cefquinome is considered to be a time-dependent antimicrobial agent, and %TMIC is the dominant PK/PD index correlated with the therapeutic efficacy [25]. The previous PK/PD studies in animal infection models have demonstrated that drug levels of β-lactam antibiotics needed to exceed the MIC for 36% to 40% of dosing interval to exert an in vivo bacteriostatic effect against Enterobacteriaceae [26]. In general, the magnitude of %TMIC to ensure a significant bactericidal or virtual elimination effect should be at least 50% of the recommended dosing interval [12, 27].

The PK/PD cutoff is crucial for guiding clinical use of antimicrobials. For most β-lactam antibiotics, the CLSI and EUCAST have established the COPD from human studies. However, as an important index reflecting the variations in host species PK and bacterial species MIC distribution, the COPD is normally significantly different between human and animals [28]. Currently, no breakpoint data of cefquinome was established for animal infections caused by E. coli. In the present study, the COPD of cefquinome against E. coli in black swans was determined to be 0.2 μg/mL at the recommended dose (2 mg/kg/24 h) based on Monte Carlo analysis, which was lower than the EUCAST clinical COPD values of cefotaxime (2 μg/mL), cefpodoxime (1 μg/mL), ceftriaxone (2 μg/mL), cefixime (1 μg/mL) and ceftibuten (1 μg/mL) against Enterobacteriaceae [29]. However, as only 49 E. coli isolates were used in our study due to the limited population of black swans, the relatively conservative COPD should be verified in a larger number of bacteria and clinical practices.

For dosage regimen assessment, Monte Carlo analysis is an important computing tool that is useful to predict the attainment of therapeutic efficacy and determine the COPD according to PK data, MIC distribution and the magnitude of PK/PD indices. As seen in Table 2, the increasing total amount of drug exerted little added therapeutic efficacy even with a considerably high simulated dose. However, after splitting into 12-h intervals, the identical daily dose could achieve a more satisfactory outcome than a single dosing. Therefore, more frequent administrations are needed for cefquinome to obtain a longer treatment period in the form of %TMIC. Routinely, a twice-daily schedule is considered a good compliance target in the clinical practice. Based on the current PK study, MIC distribution and specific PD targets, if the dose is given at 1 mg/kg twice daily, the 10,000-subject Monte Carlo simulation showed that the PTA of 95.9% and 89.2% could be achieved for %TMIC > 50% and 80% targets, respectively, against E. coli isolates in this study. In addition, taking into account the recently reported %TMIC target of 51.7% required to achieve a 2-log10 killing effect in murine thigh infection against E. coli isolates [27], cefquinome 1 mg/kg/12 h is estimated to be effective against E. coli infection in black swans.

Conclusions

To our knowledge, it is the first report about the PK and dose assessment study for cefquinome in black swans targeting E. coli strains. In the present study, we investigated pharmacokinetics and bioavailability of cefquinome following IV and IM administration in black swans. The MICs of cefquinome against 49 E. coli isolates from black swan were also determined. On the basis of PK data, MIC distribution and PD analysis, this study evaluated dose regimens of cefquinome in black swans against E. coli infections. Our findings suggest that the daily dose regimen of cefquinome at 1 mg/kg/12 h would be appropriate to achieve a satisfactory efficacy in the treatment of infections caused by E. coli in black swans.

Abbreviations

%TMIC

The duration of time that drug levels exceed the MIC in dosing interval

BW: 

Bodyweight

CLSI: 

Clinical and laboratory standards institute

EUCAST: 

European committee on antimicrobial susceptibility testing

IM: 

Intramuscular

IV: 

Intravenous

MIC: 

Minimal inhibitory concentration

PD: 

Pharmacodynamic

PK: 

Pharmacokinetic

PTA: 

Probability of target attainment

Declarations

Acknowledgements

We thank the Lv-Yuan Rare Bird Farm for providing the black swans.

Funding

This work was supported by the Aquatic Products Quality and Safety Special Project of Guangdong (Grant No. GDSCZA2015008). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

LDL and DHZ designed and conducted the experiment. QW and XFW ran the simulations and analyzed the resulting data. DHZ drafted the manuscript. All authors read, revised and approved the final manuscript.

Ethics approval and consent to participate

This study was approved by the Committee on the Ethics of Animals of South China Sea Fisheries Research Institute and the Institutional Animal Care and Use Committee of Lv-Yuan Rare Bird Farm. The owners of the rare bird farm consented for their animals to be used in this study. All experiments were conducted using the guidelines of National Standards for Laboratory Animals of China (GB 14925–2010).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Key Laboratory of Aquatic Product Processing, Ministry of Agriculture
(2)
Laboratory of Quality & Safety Risky Assessment for Aquatic Product on Storage and Preservation
(3)
Fishery Environments and Aquatic Products Quality Inspection & Testing Center of the Ministry of Agriculture
(4)
South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences

References

  1. Pizzey G, Knight F. The field guide to the birds of Australia. 9th ed. New York, NY, USA: Harper Collins Publishers, Pymble, NSW, Australia; 2012.Google Scholar
  2. Janda JM, Abbott SL. The enterobacteria. 2nd ed. Washington, DC: ASM Press; 2016.Google Scholar
  3. Yang RS, Feng Y, Lv XY, Duan JH, Chen J, Fang LX, Xia J, Liao XP, Sun J, Liu YH. Emergence of NDM-5 and MCR-1-producing Escherichia Coli clone ST648 and ST156 from a single Muscovy duck (Cairina Moschata). Antimicrob Agents Chemother. 2016;60(11):6899–902.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Limbert M, Isert D, Klesel N, Markus A, Seeger K, Seibert G, Schrinner E. Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin. Antimicrob Agents Chemother. 1991;35(1):14–9.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Committee for Medicinal Products for Veterinary Use (CVMP). Cefquinome. Summary report. EMEA/MRL/005/95. London: European Medicines Agency (EMA); 1995.Google Scholar
  6. Dumka VK, Dinakaran V, Ranjan B, Rampal S. Comparative pharmacokinetics of cefquinome following intravenous and intramuscular administration in goats. Small Rumin Res. 2013;113(1):273–7.View ArticleGoogle Scholar
  7. Zhao DH, Zhang CY, Zhang Z, Liu ZC, Liu BT, Yu JJ, Guo JP, Deng H, Liu YH. Population pharmacokinetics of cefquinome in pigs. J Vet Pharmacol Ther. 2013;36(4):313–9.View ArticlePubMedGoogle Scholar
  8. Shan Q, Yang F, Wang J, Ding H, He L, Zeng Z. Pharmacokinetic/pharmacodynamic relationship of cefquinome against Pasteurella multocida in a tissue-cage model in yellow cattle. J Vet Pharmacol Ther. 2014;37(2):178–85.View ArticlePubMedGoogle Scholar
  9. Zhou YF, Zhao DH, Yu Y, Yang X, Shi W, Peng YB, Liu YH. Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for Escherichia Coli in beagle dogs. J Vet Pharmacol Ther. 2015;38(6):543–8.View ArticlePubMedGoogle Scholar
  10. Liu B, Zhang C, Zhang X, Yang S, Yu J, Sun J, Liu Y. Pharmacokinetics and bioavailability of cefquinome in crossbred wild boars. J Vet Pharmacol Ther. 2012;35(6):611–4.View ArticlePubMedGoogle Scholar
  11. Yuan L, Sun J, Wang R, Sun L, Zhu L, Luo X, Fang B, Liu Y. Pharmacokinetics and bioavailability of cefquinome in healthy ducks. Am J Vet Res. 2011;72(1):122–6.View ArticlePubMedGoogle Scholar
  12. Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. J Vet Pharmacol Ther. 2004;27(6):467–77.View ArticlePubMedGoogle Scholar
  13. Yamaoka K, Nakagawa T, Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978;6(2):165–75.View ArticlePubMedGoogle Scholar
  14. Toutain PL, Bousquet-Melou A. Bioavailability and its assessment. J Vet Pharmacol Ther. 2004;27(6):455–66.View ArticlePubMedGoogle Scholar
  15. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; approved standard-Third Edition. Wayne: CLSI document M31-A3; 2008.Google Scholar
  16. Xie W, Zhang X, Wang T, Du S. Pharmacokinetic analysis of cefquinome in healthy chickens. Br Poult Sci. 2013;54(1):81–6.View ArticlePubMedGoogle Scholar
  17. Uney K, Altan F, Elmas M. Development and validation of a high-performance liquid chromatography method for determination of cefquinome concentrations in sheep plasma and its application to pharmacokinetic studies. Antimicrob Agents Chemother. 2011;55(2):854–9.View ArticlePubMedGoogle Scholar
  18. Li XB, Wu WX, Su D, Wang ZJ, Jiang HY, Shen JZ. Pharmacokinetics and bioavailability of cefquinome in healthy piglets. J Vet Pharmacol Ther. 2008;31(6):523–7.View ArticlePubMedGoogle Scholar
  19. El-Gendy AAM, Tohamy MA, Radi AM. Pharmacokinetic profile and some pharmacodynamic aspects of cefquinome in chickens. Beni-Suef Vet Med J. 2009;19:33–7.Google Scholar
  20. Al-Taher AY. Pharmacokinetics of Cefquinome in camels. J Anim Vet Adv. 2010;9(4):848–52.View ArticleGoogle Scholar
  21. Song IB, Kim TW, Lee HG, Kim MS, Hwang YH, Park BK, Lim JH, Yun HI. Influence of the injection site on the pharmacokinetics of cefquinome following intramuscular injection in piglets. J Vet Med Sci. 2013;75(1):89–92.View ArticlePubMedGoogle Scholar
  22. Zhang BX, Lu XX, Gu XY, Li XH, Gu MX, Zhang N, Shen XG, Ding HZ. Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids. Vet J. 2014;199(3):399–405.View ArticlePubMedGoogle Scholar
  23. Allan MJ, Thomas E. Pharmacokinetics of cefquinome after parenteral administration of an aqueous solution in the horse. J Vet Pharmacol Ther. 2003;26(Supplement 1):104.Google Scholar
  24. Hwang YH, Song IB, Lee HK, Kim TW, Kim MS, Lim JH, Park BK, Yun HI. Pharmacokinetics and bioavailability of cefquinome in rabbits following intravenous and intramuscular administration. J Vet Pharmacol Ther. 2011;34(6):618–20.View ArticlePubMedGoogle Scholar
  25. Wang J, Shan Q, Ding H, Liang C, Zeng Z. Pharmacodynamics of cefquinome in a neutropenic mouse thigh model of Staphylococcus Aureus infection. Antimicrob Agents Chemother. 2014;58(6):3008–12.View ArticlePubMedPubMed CentralGoogle Scholar
  26. Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995;22(1–2):89–96.View ArticlePubMedGoogle Scholar
  27. Shan Q, Liang C, Wang J, Li J, Zeng Z. In vivo activity of cefquinome against Escherichia Coli in the thighs of neutropenic mice. Antimicrob Agents Chemother. 2014;58(10):5943–6.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26(1):1–10. quiz 11-12View ArticlePubMedGoogle Scholar
  29. EUCAST. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.0, 2017. [http://www.eucast.org/clinical_breakpoints].

Copyright

© The Author(s). 2017

Advertisement