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1.
The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.  相似文献   

2.
1. The pharmacokinetic aspects of orbifloxacin were studied in both healthy and naturally diseased ducks after a single intravenous and intramuscular dose of 5?mg?kg?1 body weight. The serum concentrations of orbifloxacin following single intravenous and intramuscular injections were higher in diseased than in healthy ducks.

2. The disposition of orbifloxacin after a single intravenous injection was described by a two-compartment open model in both healthy and diseased ducks. Orbifloxacin was distributed and eliminated at a significantly slower rate in diseased than in healthy ducks. The total body clearance (ClB) was lower in diseased (0·131?l?kg?1?h?1) than healthy ducks (0·191?l?kg?1?h?1).

3. Following intramuscular administration of orbifloxacin, the peak serum concentration (Cmax) was higher in diseased than in healthy ducks, and this was achieved at a maximum time (tmax) of 1·114 and 0·993?h, respectively. The drug was eliminated at a significant slower rate in diseased ducks (elimination half-life t 0·5( el )?=?5·07?h) than in healthy ducks (elimination half-life t 0·5( el )?=?4·18?h).

4. These results indicate that drug elimination patterns in healthy and diseased ducks are not the same. The pharmacokinetic profile of the drug is altered in diseased ducks due to the increased serum orbifloxacin concentrations compared with clinically healthy ducks. In conclusion, 5?mg?kg?1 body weight of orbifloxacin administered as a single dose once daily could be useful in the treatment of disease caused by Pasteurella multocida pathogen in ducks.  相似文献   


3.
During October 2014, the Minnesota Department of Health was notified of five Hospital A patients with Pasteurella multocida bacteraemia; three had died. Human soft tissue infection with P. multocida typically results from cat or dog bites or scratches. Invasive infection, defined as a P. multocida isolate from a usually sterile site, is rare. We evaluated P. multocida isolations at Hospital A, compared with other Minnesota hospitals to understand invasive infection trends. A case was defined as clinically confirmed P. multocida in a Minnesota resident during 2012–2014. All hospital laboratories were queried; Fisher's exact test was used for comparison. Medical charts were reviewed for 2014 Hospital A patients with P. multocida infections. The Minnesota clinical laboratories survey response rate was 79% (63/80). At Hospital A, proportion of P. multocida isolates from usually sterile sites increased from 0% (0/2) during 2012 to 11% (1/9) during 2013, and to 86% (5/6) during 2014. The proportion of patients with P. multocida isolated from sterile sites was 35% (6/17) at Hospital A compared with 10% (58/583) statewide during 2012–2014 combined (< 0.05). Among 2014 Hospital A patients with invasive P. multocida infection, all five were men; median age was 70 (range: 44–78) years. Four were temporally clustered within a 33‐day period; three of those had bacteraemia on admission, making hospital acquisition possible in only one. Among five bacteraemia patients, four had cirrhosis and/or skin ulcerations, and three died. The proportion of invasive P. multocida cases was substantially higher at Hospital A during 2014. No epidemiologic links between patients were found. Three had known pet exposure. Collaborative educational efforts of chronically ill pet owners by physicians and veterinarians can acknowledge the health benefits of pet ownership, while minimizing risk for serious invasive zoonotic infections, including those caused by P. multocida.  相似文献   

4.
The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.  相似文献   

5.
Florfenicol is a broad‐spectrum antibacterial drug. Exopalaemon carinicauda is important in the prawn aquaculture industry in China. Florfenicol pharmacokinetics in E. carinicauda were studied at different temperatures and via different routes of administration to provide a scientific basis for the rational use of drugs for E. carinicauda production. At water temperatures of 22 ± 0.4°C and 28 ± 0.3°C, after intramuscular (IM) injection and oral (per ora (PO)) administration of florfenicol at 10 mg/kg body weight (BW) and 30 mg/kg BW, respectively, the florfenicol concentration in the plasma, hepatopancreas, gills, muscles, and carapace of E. carinicauda was determined by high‐performance liquid chromatography. After IM injection at different temperatures, the metabolism of florfenicol in E. carinicauda conformed to a two‐compartment open model with zero‐order absorption. After PO administration, the metabolism of florfenicol in E. carinicauda was consistent with a two‐compartment open model with first‐order absorption. Using an identical administration route but different water temperatures, the metabolism of florfenicol in E. carinicauda was quite different. Overall, florfenicol was absorbed rapidly and distributed widely in E. carinicauda, but elimination was slow and the bioavailability was not high. A low temperature and PO administration resulted in a low elimination rate.  相似文献   

6.
7.
To explore the in vivo antimicrobial activity of cefquinome against Pasteurella multocida in piglets, a piglet tissue cage infection model was used in this study. After the population of P. multocida reached 107 CFU/mL in a tissue cage, piglets received an intramuscular administration of cefquinome at 0.2, 0.4, 0.8, 1, 2, and 4 mg/kg once daily for 3 days. To assess the tissue cage pharmacokinetics (PKTCF) of cefquinome, tissue cage fluid was collected for cefquinome analysis at 1, 3, 6, 9, 12, and 24 hr after each of the 3 daily drug administrations. Bacteria were counted every 24 hr after drug administration and at 48 and 72 hr after the last administration. Evaluation of the relationship between pharmacokinetic/pharmacodynamic (PK/PD) parameters and the antibacterial effect showed that the surrogate of %> minimum inhibitory concentration (MIC) (R2 = 0.981) was the best PK/PD index that correlated with effectiveness of cefquinome against P. multocida. The respective values of %> MIC required for continuous 1/3‐log, 1/2‐log, and 1‐log reductions were 14.23, 34.45, and 73.44%, respectively, during each 24‐hr treatment period. In conclusion, cefquinome exhibited a potent antibacterial effect against P. multocida. When %> MIC reached 73.44%, cefquinome exhibited a bactericidal effect against P. multocida after three successive daily administrations.  相似文献   

8.
For clinical isolates of bovine Mannheimia haemolytica and Pasteurella multocida, this study reports minimum inhibitory concentration (MIC) differences for tetracycline, oxytetracycline and doxycycline between cation‐adjusted Mueller‐Hinton broth (CAMHB), foetal bovine serum (FBS) and Roswell Park Memorial Institute (RPMI) medium. MICs were determined according to CLSI standards and additionally using five overlapping sets of twofold dilutions. Matrix effect: (a) free drug MICs and minimum bactericidal concentrations (MBC) for all drugs were significantly higher in FBS than in CAMHB for both pathogens (p < 0.001); (b) MICs and MBCs were higher for CAMHB and FBS compared to RPMI for P. multocida only. Net growth rate for P. multocida in CAMHB was significantly slower than in FBS and higher than in RPMI, correlating to MIC and MBC ranking. Drug effect: doxycycline MICs and MBCs were significantly lower (p < 0.001) in both CAMHB and FBS than tetracycline and oxytetracycline for both pathogens. Only for M. haemolytica were oxytetracycline MIC and MBC significantly lower than tetracycline, precluding the use of tetracycline to predict oxytetracycline susceptibility in this species. Determining potencies of tetracyclines in a physiological medium, such as FBS, is proposed, when the objective is correlation with pharmacokinetic data for dosage determination.  相似文献   

9.
Avian pathogenic Escherichia coli could cause localized and systemic infection in the poultry, and danofloxacin is usually used to treat avian colibacillosis through oral administration. To promote prudent use of danofloxacin and reduce the emergence of drug‐resistant E. coli strains, it is necessary to understand the population pharmacokinetics (PopPK) of danofloxacin in chicken intestines. In this study, reversed‐phase high performance liquid chromatography (HPLC) with fluorescence detection was used to detect the concentrations of danofloxacin in the contents of duodenum, jejunum, and ileum of the healthy and infected chickens after single oral administration (5 mg/kg body weight). Then, the PopPK of danofloxacin in intestines were analyzed using NONMEM software. As a result, a two‐compartment PK model best described the time‐concentration profile of duodenal, jejunal, and ileal contents. Interestingly, absorption rate (Ka), distribution volume (V), and clearance (CL) for danofloxacin from duodenal, jejunal to ileal contents were sequentially decreased in the healthy chickens. However, the trend of Ka, V, and CL of danofloxacin was changed dramatically in the intestine of infected chickens. Ka and V of danofloxacin in the jejunum were higher than in the ileum and duodenum. Compared with healthy chickens, Ka and V of danofloxacin in the duodenum decreased significantly, while increased in jejunum, respectively. It has been noted that Ka decreased and V increased in the ileum of infected chickens. Besides, CL in the duodenum, jejunum, and ileum of infected chickens was, respectively, lower than those of healthy chickens. Interestingly, the relative bioavailability (F) of danofloxacin in the ileum was relatively higher in both healthy and infected chickens. In addition, F in the duodenal, jejunal, and ileal contents of infected chickens was respectively higher than healthy chickens. In summary, the PopPK for danofloxacin in infected chicken intestines was quite different from healthy chickens. The absorption, distribution, and clearance of danofloxacin in healthy chickens decreased from duodenum to jejunum and to ileum. Moreover, the pharmacokinetic characteristics in the intestine of infected chickens changed significantly, and the pharmacokinetic characteristics in the ileum can be used as a representative of all intestinal segments.  相似文献   

10.
Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr, AUC0–∞, Tmax, T1/2, Cmax, CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.  相似文献   

11.
健康白羽肉鸡20只,随机分为A、B两组,以20mg/kg的剂量单次灌服两种工艺的20%氟苯尼考粉。并于给药后不同时间点从翅下静脉采血,采用已建立的UPLC-MS/MS测定血浆中的药物浓度。采用 WinNonlin 5. 2. 1 药动学分析软件的非房室模型拟合血药浓度-时间数据。结果显示:A组达峰时间(Tmax)和达峰浓度(Cmax)分别为1.675±0.782 h、1073.20±425.72 ng/mL,平均消除半衰期T1/2λz约为4.729±3.347 h,平均曲线下面积 (AUClast) 为 4498.76±2596.16 h?ng/mL;B组达峰时间(Tmax)和达峰浓度(Cmax)分别为1.523±1.723 h、4654.64±1669.75 ng/mL,平均消除半衰期T1/2λz约为2.193±1.515 h,平均曲线下面积 (AUClast)为15392.84±2586.10 ng/mL;相对生物利用度约为342.16%。结果表明,采用环糊精包合工艺的氟苯尼考粉的生物利用度显著高于普通工艺的氟苯尼考粉。  相似文献   

12.
氟苯尼考对鸡多杀性巴氏杆菌感染的疗效试验   总被引:1,自引:0,他引:1  
以试管肉汤两倍稀释法测定氟苯尼考和氯霉素对鸡多杀性巴氏杆菌的最小抑菌浓度,然后对实验性鸡多杀性巴杆菌感染进行内服或肌注给药3d(每天2次)的治疗试验。结果表明,氟苯尼考和氯霉素对鸡多杀性巴氏杆菌的最小抑菌浓度分别是0.5和1.0μg/mL。以20、40、80mg/kgBW氟苯尼考和40mg/kgBW氯霉素的剂量给鸡内服给药后,对鸡多杀性巴氏杆菌感染的治愈率分别为93.3%、100%、100%及70%;相同剂量肌注给药的治愈率分别为86.7%、100%、100%和83.3%,而感染对照组的死亡率为90.0%。  相似文献   

13.
For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion‐limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion‐limited lung, flow‐limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration–time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.  相似文献   

14.
[目的]观察抗菌药物氟苯尼考对多杀性巴氏杆菌的体外抑菌效果,评价其对人工感染多杀性巴氏杆菌小白鼠的防治效果。[方法]采用微量肉汤稀释法测定临床常用的9种抗菌药物对多杀性巴氏杆菌的抑菌效果,筛选敏感抗菌药物,进一步选择小白鼠开展预防试验和治疗试验,观察抗菌药物对人工感染多杀性巴氏杆菌小白鼠的防治效果。[结果]在9种常见的抗菌药物中,对多杀性巴氏杆菌抑菌效果最好的是氟苯尼考和多西环素,2种药物的MIC为1 μg/mL,MBC为2 μg/mL;抑菌效果最差的是延胡索酸泰妙菌素,MIC为64 μg/mL,MBC为128 μg/mL。利用多杀性巴氏杆菌人工感染小白鼠,治疗试验与预防试验均设置阴性对照组(注射生理盐水)、阳性对照组(攻毒细菌)以及药物治疗或预防组(攻毒细菌+氟苯尼考);治疗试验获得氟苯尼考的保护率为78.6%,预防试验的保护率为84.6%。[结论]氟苯尼考对人工感染多杀性巴氏杆菌小白鼠有较好的防治效果。  相似文献   

15.
The objective of this work was to manufacture an enteric formulation of florfenicol (FF) using hot‐melt extrusion (HME) technology and to evaluate its in vitro dissolution and in vivo pharmacokinetics. For the HME process, hypromellose acetate succinate LG (HPMCAS‐LG) was the enteric polymer mixed with FF, and the two components were extruded with a standard screw configuration at a speed of 50 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X‐ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT‐IR) were performed to characterize the HME extrudate. The release percentage of the enteric formulation in the acidic stage was <10% of the loaded FF, whereas that in the phosphate buffer stage was >80%. Pharmacokinetic evaluations in swine revealed that the enteric formulation had a longer t1/2λ and MRT than commercially available FF powder (FULAIKA®), indicating that the novel formulation exhibited enteric and sustained release properties. Compared with the commercial product, the relative bioavailability of the enteric formulation reached up to 117.2%. This study suggests that this formulation may have potential for future commercialization.  相似文献   

16.
Increase in the number of small‐scale backyard poultry flocks in the USA has substantially increased human‐to‐live poultry contact, leading to increased public health risks of the transmission of multi‐drug resistant (MDR) zoonotic and food‐borne bacteria. The objective of this study was to detect the occurrence of Salmonella and MDR Gram‐negative bacteria (GNB) in the backyard poultry flock environment. A total of 34 backyard poultry flocks in Washington State (WA) were sampled. From each flock, one composite coop sample and three drag swabs from nest floor, waterer‐feeder, and a random site with visible faecal smearing, respectively, were collected. The samples were processed for isolation of Salmonella and other fermenting and non‐fermenting GNB under ceftiofur selection. Each isolate was identified to species level using MALDI‐TOFF and tested for resistance against 16 antibiotics belonging to eight antibiotic classes. Salmonella serovar 1,4,[5],12:i:‐ was isolated from one (3%) out of 34 flocks. Additionally, a total of 133 ceftiofur resistant (CefR) GNB including Escherichia coli (53), Acinetobacter spp. (45), Pseudomonas spp. (22), Achromobacter spp. (8), Bordetella trematum (1), Hafnia alvei (1), Ochrobactrum intermedium (1), Raoultella ornithinolytica (1), and Stenotrophomonas maltophilia (1) were isolated. Of these, 110 (82%) isolates displayed MDR. Each flock was found positive for the presence of one or more CefR GNB. Several MDR E. coli (n = 15) were identified as extended‐spectrum β‐lactamase (ESBL) positive. Carbapenem resistance was detected in non‐fermenting GNB including Acinetobacter spp. (n = 20), Pseudomonas spp. (n = 11) and Stenotrophomonas maltophila (n = 1). ESBL positive E. coli and carbapenem resistant non‐fermenting GNB are widespread in the backyard poultry flock environment in WA State. These GNB are known to cause opportunistic infections, especially in immunocompromised hosts. Better understanding of the ecology and epidemiology of these GNB in the backyard poultry flock settings is needed to identify potential risks of transmission to people in proximity.  相似文献   

17.
A study on bioavailability and pharmacokinetics of florfenicol was conducted in 20 crossbred healthy sheep following a single intravenous (i.v.) and intramuscular (i.m.) doses of 20 and 30 mg/kg body weight (b.w.). Florfenicol concentrations in serum were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm in which serum samples were spiked with chloramphenicol as internal standard. Serum concentration-time data after i.v. administration were best described by a three-compartment open model with values for the distribution half-lives (T(1/2alpha)) 1.51 +/- 0.06 and 1.59 +/- 0.10 h, elimination half-lives (T(1/2beta)) 18.83 +/- 6.76 and 18.71 +/- 1.85 h, total body clearance (Cl(B)) 0.26 +/- 0.03 and 0.25 +/- 0.01 L/kg/h, volume of distribution at steady-state (V(d(ss))) 1.86 +/- 0.11 and 1.71 +/- 0.20 L/kg, area under curve (AUC) 76.31 +/- 9.17 and 119.21 +/- 2.05 microg.h/mL after i.v. injections of 20 and 30 mg/kg b.w. respectively. Serum concentration-time data after i.m. administration were adequately described by a one-compartment open model. The pharmacokinetic parameters were distribution half-lives (T(1/2k(a) )) 0.27 +/- 0.03 and 0.25 +/- 0.09 h, elimination half-lives (T(1/2k(e) )) 10.34 +/- 1.11 and 9.57 +/- 2.84 h, maximum concentrations (C(max)) 4.13 +/- 0.29 and 7.04 +/- 1.61 microg/mL, area under curve (AUC) 67.95 +/- 9.61 and 101.95 +/- 8.92 microg.h/mL, bioavailability (F) 89.04% and 85.52% after i.m. injections of 20 and 30 mg/kg b.w. respectively.  相似文献   

18.
19.
Cryptosporidium and Enterocytozoon are common opportunistic pathogens in HIV+ patients in developing countries, especially those do not have access to antiretroviral therapy. To determine the distribution of genotypes/subtypes of Cryptosporidium and Enterocytozoon bieneusi, faecal specimens were collected from 132 HIV+ persons attending a tertiary hospital in Ibadan, Nigeria. By polymerase chain reaction, eight and ten patients were identified as positive for Cryptosporidium spp. and E. bieneusi, respectively. Seven of the Cryptosporidium specimens were identified as C. hominis, while the remaining one as the new species C. viatorum recently identified in the United Kingdom. DNA sequencing of the 60‐kDa glycoprotein gene showed that the C. hominis belonged to three common subtype families: Ia (in three patients), Ib (in one patient) and Ie (in one patient). In contrast, DNA sequencing of the E. bieneusi internal transcribed spacer products showed the occurrence of genotypes associated with both humans (Peru 8 in one patient, Nig2 in two patients and a new genotype in one patient) and animals (D in one patient and Type IV in five patients). Low CD4+ cell count was identified as a risk factor for both cryptosporidiosis and microsporidiosis.  相似文献   

20.
The purpose of this retrospective, multicentre case series was to describe the outcome following surgery and/or radiation of spinal meningiomas and nerve sheath tumours (NSTs) based upon treatment modality, with a specific aim to evaluate the survival times and time to recurrence following treatment for each histopathological diagnosis. Our hypothesis was that the addition of radiation therapy modalities to treatment will yield longer time to recurrence of clinical signs and survival time. Thirty‐four dogs met the inclusion criteria of histopathologically diagnosed extramedullary spinal meningioma or NST. Sixteen extramedullary spinal meningiomas and 18 NSTs were diagnosed. A diagnosis of meningioma was associated with a significantly longer survival time compared with NSTs, with median survival times (MST) of 508 days (95% confidence interval [CI]: 66‐881) vs 187 days (95% CI: 76‐433; P = .02). Dogs (seven) treated with stereotactic radiation therapy (SRT) for recurrence after surgery alone or SRT alone as their initial treatment gained an additional 125 to 346 days survival time.  相似文献   

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