盐酸吡利霉素乳房灌注剂安全性试验

<正>吡利霉素是一种具有抗革兰阳性菌活性的林肯霉素类抗生素,通过与细菌核糖核酸(RNA)50S亚基结合起作用,从而干扰细菌内蛋白质合成,达到杀菌和抑菌的目的。吡利霉素具有抗葡萄球菌(金黄色葡萄球菌等)及抗链球菌(如无乳链球菌、停乳链球菌、乳房链球菌)的体外和临床活性,主要用于葡萄球菌、链球菌引起的奶牛隐性和临床型乳房炎。国产盐酸吡利霉素乳房灌注剂由浙江海正药业股份有限公司开发研制。本试验旨在应用健康     

4种药物对徐州地区奶牛乳房炎防治试验

对徐州地区6个奶牛饲养场,分别筛选临床型奶牛乳房炎和隐性奶牛乳房炎病例各80例,用4种不同的药物组合分别进行治疗,以观察治疗效果。结果表明:中西结合的混悬制剂复方阿莫西林乳房灌注剂乳管注入效果最佳,其对临床型奶牛乳房炎和隐性奶牛乳房炎的治愈率分别达到45%和60%。同时,对部分奶牛场奶牛进行综合性预防试验,减少了奶牛乳房炎的发病。     

国产盐酸吡利霉素乳区注入剂治疗奶牛乳房炎的效果观察

本试验通过与进口盐酸吡利霉素的对比,研究确定了国产盐酸吡利霉素对葡萄球菌、链球菌性乳房炎的治疗效果,旨在为药物的临床应用提供依据。结果表明,隐性乳房炎试验组和对照组的总有效率均为100%(12/12和10/10),治愈率分别为83.33%(10/12)和90%(9/10),平均用药次数为1.65次和1.5次;临床型乳房炎试验组的25mg组、50mg组、75mg组和对照组的总有效率分别为50%(5/10)、75%(10/12)、85.71%(12/14)和80%(8/10);治愈率为30%(3/10)、58.33%(7/12)、64.29%(9/14)和60%(6/10);平均用药次数为6次、4.9次、5.57次和5次。经卡方检验,试验组和对照组之间治愈率、有效率均无显著差异。可以得出国产盐酸吡利霉素对葡萄球菌和链球菌引起的隐性乳房炎和临床型乳房炎,均有良好的治疗效果。     

应用左旋咪唑治疗奶牛隐性乳房炎

奶牛隐性乳房炎对奶牛业生产危害较严重。据调查,全市奶牛隐性乳房炎污染率在36—71%之间。检验方法用C.M.T法。为治疗奶牛隐性乳房炎,我们在黑河市奶牛场进行盐酸左旋咪唑药物治疗试验,现报告如下: 一、试验材料及方法盐酸左旋咪唑:上海延安制药厂生产     

宁夏地区奶牛乳房炎源阴道加德纳菌分离鉴定及耐药性分析

为了研究奶牛乳房炎源阴道加德纳菌(GV)的耐药情况,从宁夏部分奶牛场采集临床型乳房炎奶牛乳样94份、隐性乳房炎奶牛乳样70份进行细菌分离鉴定,得到2株GV(均来自于临床型乳房炎奶牛乳样);动物试验结果表明GV对奶牛乳房炎没有致病性;药敏试验结果表明分离菌对哌拉西林、万古霉素、四环素、克林霉素耐药,对阿莫西林中介,对其他药物均敏感。     

唐山地区奶牛隐性乳房炎病原体调查与防治

本试验调查了唐山周边地区奶牛隐性乳房炎主要病原菌的流行状况,并分离致病菌,确定主要病原微生物是无乳链球菌和金黄色葡萄球菌。并对2种主要致病菌进行体外药敏试验,根据药物的敏感程度研究组方。选用30头患隐性乳房炎的阳性奶牛进行体内治疗试验,试验设为3组,经统计治疗结果,得出最佳的治疗药物为盐酸克林霉素注射液,治愈率为90%。     

沙大净系列治疗奶牛乳房炎的研究

本试验采用复方中药沙大净系列对奶牛隐性乳房炎和临床型乳房炎进行治疗试验,并与传统西药疗法进行比较。结果表明,沙大净系列产品治疗奶牛乳房炎具有明显的效果。     

辽宁某牛场奶牛隐性乳房炎源链球菌耐药性研究

为了解辽宁阜新某奶牛场奶牛隐性乳房炎发生情况,采用体细胞计数法对奶牛场中94头临床表现健康的奶牛进行隐性乳房炎筛查,对检测后的阳性乳样进行链球菌的分离鉴定,并采用微量肉汤稀释法对分离所得的链球菌进行药敏试验。结果显示:该牛场奶牛隐性乳房炎的检出率为48.94%;对34株奶牛隐性乳房炎链球菌分离株进行体外药敏试验,发现菌株对头孢氨苄、磺胺间甲氧嘧啶和磺胺甲基异恶唑耐药率最高(100%);对苯唑西林、阿奇霉素、林可霉素、多西环素、土霉素、红霉素的耐药率均在82.4%以上;对氨苄西林、阿莫西林和环丙沙星较敏感,敏感率分别为44.1%、50.0%及52.9%。结果表明:该奶牛场隐性乳房炎源链球菌多重耐药现象严重。     

奶牛隐性乳房炎疗效对比试验

应用中药复方、单味蒲公英、硫酸庆大霉素合盐酸普鲁卡因，后海穴注射及盐酸左旋咪唑配合鱼腥草注射液肌肉注射四种方法，对４２头奶牛的隐性乳房炎进行了对比治疗试验，结果表明，左旋咪唑配合鱼腥草注射液肌肉注射及中药复方是治疗该病的最佳方法。     

辽宁阜新地区奶牛隐性乳房炎调查及大肠埃希菌药敏试验

为调查辽宁阜新地区奶牛隐性乳房炎患病情况,选取该地区某规模化养殖场,对190头泌乳期奶牛进行体细胞检测。结果显示,该地区奶牛隐性乳房炎患病率为34.2%,乳区阳性率为8.5%。采用微量肉汤稀释法检测阳性乳样分离到的大肠埃希菌对14种抗菌药物的敏感性。结果表明,26株隐性乳房炎大肠埃希菌分离株对甲砜霉素和头孢氨苄耐药率为100%、氟苯尼考73.1%、土霉素65.4%、头孢唑啉57.7%、阿莫西林30.8%、四环素30.8%、恩诺沙星26.9%、阿奇霉素19.2%、氧氟沙星15.4%、多西环素11.5%、环丙沙星11.5%,对头孢噻呋和庆大霉素耐药率为0。建议该地区根据药敏试验结果选取药物进行治疗。     

Efficacy of extended pirlimycin therapy for treatment of experimentally induced Streptococcus uberis intramammary infections in lactating dairy cattle

Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, around the time of calving, and during early lactation. Strategies for controlling S. uberis mastitis have not received adequate research attention and are therefore poorly defined and inadequate. Objectives of the present study were to evaluate the efficacy of extended therapy regimens with pirlimycin for treatment of experimentally induced S. uberis intramammary infections in lactating dairy cows during early lactation and to evaluate the usefulness of the S. uberis experimental infection model for evaluating antimicrobial efficacy in dairy cows. The efficacy of extended pirlimycin intramammary therapy regimens was investigated in 103 mammary glands of 68 dairy cows that became infected following experimental challenge with S. uberis during early lactation. Cows infected with S. uberis in one or both experimentally challenged mammary glands were randomly allocated to three groups, representing three different treatment regimens with pirlimycin, including 2-day (n = 21 cows, 31 mammary quarters), 5-day (n = 21 cows, 32 quarters), and 8-day (n = 26 cows, 40 quarters). For all groups, pirlimycin was administered at a rate of 50 mg of pirlimycin hydrochloride via intramammary infusion. A cure was defined as an experimentally infected mammary gland that was treated with pirlimycin and was bacteriologically negative for the presence of S. uberis at 7, 14, 21, and 28 days after treatment. Experimental S. uberis intramammary infections were eliminated in 58.1% of the infected quarters treated with the pirlimycin 2-day regimen, 68.8% for the 5-day regimen, and 80.0% for the 8-day regimen. Significant differences (P <.05) in efficacy were observed between the 2-day and 8-day treatment regimens. The number of somatic cells in milk decreased significantly following therapy in quarters for which treatment was successful in eliminating S. uberis. However, there was no evidence to suggest that extended therapy with pirlimycin resulted in a greater reduction in somatic cell counts in milk than the 2-day treatment. The S. uberis experimental infection model was a rapid and effective means of evaluating antimicrobial efficacy during early lactation at a time when mammary glands are highly susceptible to S. uberis intramammary infection.     

Efficacy of extended intramammary ceftiofur therapy against mild to moderate clinical mastitis in Holstein dairy cows: A randomized clinical trial

Few studies have investigated the efficacy of extended ceftiofur therapy and none have focused on extended therapy for naturally occurring clinical mastitis. The objective of this study was to compare the efficacy of extended intramammary ceftiofur therapy of 8 d duration with a standard 2-day regimen for the treatment of naturally occurring mild to moderate clinical mastitis in lactating dairy cows. Holstein cows from 22 dairy herds (n = 241) were randomly allocated to the 2 treatment groups. For each case of mastitis, 125 mg of ceftiofur hydrochloride was administered intramammary once a day for 2 or 8 d. Clinical cure, 21 d after the last treatment, was 89% (98/110) in each group. Bacteriological cure 21 d after the last treatment for the 2- and 8-day regimens were 32% (15/47) and 61% (25/41), respectively, for all bacteria (P = 0.007), 64% (9/14) and 82% (9/11), respectively, for streptococci (P = 0.50), and 0% (0/20) and 47% (9/19), respectively, for Staphylococcus aureus (P = 0.0004). There were no statistical differences between groups for new intramammary infections. Overall, ceftiofur extended therapy increased cure when compared to a 2-day regimen for the treatment of naturally occurring mild to moderate clinical mastitis in lactating dairy cows.     

Comparison of plasma pharmacokinetics and bioavailability of ceftiofur sodium and ceftiofur hydrochloride in pigs after a single intramuscular injection

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.     

A comprehensive review of ceftiofur sodium and hydrochloride formulations for treatment of acute bovine foot rot

Seven well-controlled studies conducted under multiple management conditions demonstrated that ceftiofur, a late-generation veterinary parenteral cephalosporin, is effective for the treatment of bovine foot rot in beef and dairy cattle. Two preliminary dosage titration studies using a challenge model compared the efficacy of ceftiofur (1.1 mg or 2.2 mg ceftiofur equivalents [CE]/kg administered once daily for 3 days) with placebo. One preliminary clinical study evaluated the efficacy of ceftiofur sodium (1.0 mg CE/kg once daily for 3 days) in lactating dairy cows. Two clinical trials evaluated the efficacy of ceftiofur sodium versus placebo for naturally occurring foot rot, and two trials compared the efficacy of ceftiofur sodium or hydrochloride (1.0 mg CE/kg) with oxytetracycline (6.6 or 10 mg/kg), each administered once daily for 3 days, for treatment of acute foot rot in beef cattle. All trials demonstrated the efficacy of ceftiofur for treatment of acute bovine foot rot. Ceftiofur and oxytetracycline were comparable in efficacy, with ceftiofur having excellent injection-site tolerance and short or no milk discard or preslaughter withdrawal.     

Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice

Ceftiofur sodium, a broad-spectrum beta-lactamase-resistant cephalosporin, was evaluated in vitro and in vivo in mice. Ceftiofur is the sodium salt of (6R, 7R)-7[( 2-amino-4-thiazolyl)-Z- (methoxyimino)acetyl]amino)-3-[( (2-furanylcarbonyl)thio]methyl)-8-oxo-5- thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylate. Minimal inhibitory concentration values were obtained with 264 strains representing 9 genera and 17 species of bacterial pathogens from cattle, swine, sheep, horses, poultry, dogs, cats, and human beings. Ceftiofur was more active than was ampicillin against all strains tested including beta-lactamase-producing organisms. In mice with systemic infections, ceftiofur was more active than or equivalent to ampicillin, cephalothin, cefamandole, cloxacillin, cefoperazone, or pirlimycin. These protection tests included infections with Escherichia coli, Haemophilus pleuropneumoniae, H somnus, Pasteurella haemolytica, P multocida, Salmonella typhimurium, or Staphylococcus aureus. In infant mice with E coli-induced lethal diarrhea and in mice with S aureus and E coli-induced mastitis, ceftiofur was comparable or more active than was ampicillin.     

Effect of prepartum intramammary treatment with pirlimycin hydrochloride on prevalence of early first-lactation mastitis in dairy heifers

OBJECTIVE: To determine whether prepartum intramammary treatment of dairy heifers with pirlimycin hydrochloride would reduce the prevalence of intramammary infection (IMI) and lower the somatic cell count (SCC) during early lactation or improve 305-day mature equivalent milk production. DESIGN: Prospective clinical trial. ANIMALS: 183 Holstein-Friesian heifers (663 quarters) from 2 dairy farms. PROCEDURE: Heifers were assigned to treatment and control groups. Treated heifers received a single 50-mg dose of pirlimycin in each mammary quarter approximately 10 to 14 days prior to parturition. Prepartum mammary gland secretions and postpartum milk samples were collected for bacterial culture. Postpartum milk samples were also collected for determination of SCC or California mastitis testing and were tested for pirlimycin residues. Mature equivalent 305-day milk production data were recorded. RESULTS: Treated heifers in herd A had a higher overall cure rate, higher cure rates for IMI caused by coagulase-negative staphylococci (CNS) and Staphylococcus aureus, lower SCC, and lower prevalence of chronic IMI, compared with control heifers. Treated heifers in herd B had a higher overall cure rate and cure rate for IMI caused by CNS, compared with control heifers, but postpartum California mastitis test scores and prevalence of chronic IMI did not differ between groups. Mature equivalent 305-day milk production did not differ between herds or treatment groups. No pirlimycin residues were detected in postpartum milk samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that prepartum treatment of dairy heifers with pirlimycin may reduce the prevalence of early lactation IMI, particularly IMI caused by CNS, without causing pirlimycin residues in milk.     

复方盐酸头孢噻呋混悬剂的药代动力学研究

利用药物动力学的方法考察复方盐酸头孢噻呋混悬剂是否具备缓释长效的特点,同时研究鱼腥草油对头孢噻呋药代动力学的影响。36只SPF大鼠随机平均分成三组:A组单剂量注射复方盐酸头孢噻呋混悬剂,B组单剂量注射盐酸头孢噻呋混悬剂,C组单剂量注射头孢噻呋钠粉针;三组注射剂量均为50 mg/(kg.bw)。采用反相高效液相色谱内标法测定血浆药物浓度,并以DAS2.0药动学程序和SPSS(11.0)统计软件对所得数据进行分析。A、B、C组药时数据均符合一级吸收二室模型(权重=1/cc),主要动力学参数如下:A组:T1/2Ka=(1.253±0.100)h,Tpeak=(2.000±0.000)h,Cmax=(35.203±5.732)mg/L,AUC=(229.51±18.278)mg.h/L;B组:T1/2Ka=(0.341±0.090)h,Tpeak=(1.000±0.000)h,Cmax=(43.919±1.51)mg/L,AUC=(188.488±9.611)mg.h/L;C组:T1/2Ka=(0.044±0.012)h,Tpeak=(0.167±0.000)h,Cmax=(159.091±19.971)mg/L,AUC=(128.554±6.625)mg.h/L。实验数据表明,复方盐酸头孢噻呋混悬剂肌肉注射后,其药物动力学特征表现为吸收缓慢,血药浓度平稳,消除半衰期延长,生物利用度高等特点,在临床上注射1次,连用3 d,可以维持有效血液浓度。     

Acute coliform mastitis in buffaloes (Bubalus bubalis): Clinical findings and treatment outcomes

This report was delineated to study the clinical, bacteriological and therapeutic aspects concerned with acute coliform mastitis in buffaloes. Bacteriological examination of 80 quarter milk samples obtained aseptically from 56 buffaloes with acute mastitis revealed that coliform bacteria was the most common pathogen (45 cases) followed by Staphylococcus aureus (seven cases) then Streptococcus uberis (three cases), and Streptococcus agalactiae (one case). Clinically, hotness, swelling and painful reaction with serous excretion containing clots was recorded in buffaloes with coliform mastitis. The efficacy of ceftiofur was evaluated in the treatment of buffaloes with acute coliform mastitis. Parenteral ceftiofur neither improved clinical signs nor returned milk to pre-infection production level, whereas intramammary ceftiofur and combination of intramammary with parenteral ceftiofur improved the clinical signs in 10/15 and 12/15 buffaloes, respectively. On quarter level, 3/17, 12/17 and 15/21 quarters recovered in groups received parenteral, intramammary and combination therapy, respectively. This study demonstrates that systemic ceftofur is not effective in the treatment of clinical coliform mastitis in buffaloes.     

Preparation and pharmacokinetics of ceftiofur sodium liposomes in cows

Liu, S., Guo, D., Guo, Y., Zhou, W. Preparation and pharmacokinetics of ceftiofur sodium liposomes in cows. J. vet. Pharmacol. Therap. 34 , 35–41. The objective of this study was to prepare ceftiofur sodium liposomes and assess their physical properties, stability, antibacterial effects, and pharmacokinetics. These liposomes appeared as a milky, light yellow suspension with encapsulation efficiency at 57.2 ± 1.17%, and there were no significant changes in all estimated indexes at 4 °C for 90 days. The minimum inhibitory concentrations of liposomes were all 1/4th that of ceftiofur sodium against Streptococcus suis, Staphylococcus aureus, Escherichia coli, and Salmonella enteritidis. Six healthy, adult cows in two treatment groups were dosed intravenously with ceftiofur sodium liposomes and ceftiofur sodium, serial blood samples collected, and plasma concentrations determined by high performance liquid chromatography. Intravenous plasma concentration profiles of liposomes best fit a two‐compartment model and the elimination half‐life was 2.11 times that of ceftiofur sodium. Thus, this liposome preparation provided therapeutically effective plasma concentrations for a longer duration than with the drug alone, making it more effective and convenient for use in treating bovine mastitis that requires long duration maintenance of therapeutic plasma concentrations.     

Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows

OBJECTIVE: To determine the elimination kinetics of ceftiofur hydrochloride in milk after intramammary administration in lactating dairy cows. DESIGN: Prospective study. ANIMALS: 5 lactating dairy cows. PROCEDURE: After collection of baseline milk samples, 300 mg (6 mL) of ceftiofur was infused into the left front and right rear mammary gland quarters of each cow. Approximately 12 hours later, an additional 300 mg of ceftiofur was administered into the same mammary gland quarters after milking. Milk samples were collected from each mammary gland quarter every 12 hours for 10 days. Concentrations of ceftiofur and its metabolites in each milk sample were determined to assess the rate of ceftiofur elimination. RESULTS: Although there were considerable variations among mammary gland quarters and individual cows, ceftiofur concentrations in milk from all treated mammary gland quarters were less than the tolerance (0.1 microg/mL) set by the FDA by 168 hours (7 days) after the last intramammary administration of ceftiofur. No drug concentrations were detected in milk samples beyond this period. Ceftiofur was not detected in any milk samples from nontreated mammary gland quarters throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur administered by the intramammary route as an extra-label treatment for mastitis in dairy cows reaches concentrations in milk greater than the tolerance set by the FDA. Results indicated that milk from treated mammary gland quarters should be discarded for a minimum of 7 days after intramammary administration of ceftiofur. Elimination of ceftiofur may be correlated with milk production, and cows producing smaller volumes of milk may have prolonged withdrawal times.