恩诺沙星对土壤细菌数量及耐药性的影响

兽药吸收进入动物机体后,少部分药物将残留于动物组织细胞内,而大部分药物将排泄到体外,最终进入生态环境中,且可能造成环境污染。为了解恩诺沙星在环境中残留对土壤细菌的影响,在恩诺沙星作用于土壤后第35天,对纯培养法分离的土壤细菌进行了计数,并对土壤细菌进行了抗菌药物敏感性试验。结果表明,添加药物组的细菌总数均低于空白对照组,且药物浓度越高,细菌数量越少;在供试的19种抗菌药中,恩诺沙星敏感菌对其中的16种药物的敏感性均显著高于恩诺沙星耐药菌（P〈0.01）。     

徐州地区猪源致病性大肠杆菌耐药性检测

为了考察徐州地区猪源致病性大肠杆菌的耐药情况,采用传统微生物法对徐州周边地区52株猪大肠杆菌进行分离鉴定,试管二倍稀释法测定细菌对药物的敏感性,提取耐药菌质粒DNA,PCR扩增耐药基因目的片段。结果表明,氟苯尼考和阿莫西林对徐州周边临床大肠杆菌分离株的最小抑菌浓度(MIC)值与标准菌株相比较,分别提高20～512倍、10～800倍,个别临床分离株对恩诺沙星的MIC值高达80μg/mL,对头孢曲松的MIC值高达80μg/mL,对安普霉素的MIC值高达320μg/mL;经PCR检测临床分离株均扩增出氟苯尼考Flor耐药基因,Tem型ESBLs耐药基因目的片段。说明徐州周边临床大肠杆菌对氟苯尼考和阿莫西林已产生严重耐药性,对恩诺沙星和安普霉素已经耐药,但大部分菌株对头孢曲松敏感。提示徐州周边地区猪场应科学合理、有计划地轮换使用不同药物。     

豫北地区临床分离鸡大肠杆菌的体外药物敏感性测定

为了有效地治疗鸡大肠杆菌病,采用微量倍比稀释方法测定了17种抗菌药物对临床分离的豫北地区15株鸡大肠杆菌的体外最小抑菌浓度(MIC),并根据其MIC及MIC范围(MICRange)使用SPSS 13.0中Probit过程计算出17种抗菌药物的MIC50和MIC90.结果表明:多粘菌素B的抑菌作用最强,MIC50、MIC90分别为0.11、0.87 μg/mL;加替沙星的抑菌作用次之,MIC50、MIC90分别为2.53、3.88 μg/mL,其它3种药物恩诺沙星、左氧氟沙星、环丙沙星的抑菌作用相当,但不及加替沙星,MIC50、MIC90分别为10.11～11.79 μg/mL、15.16～21.13 μg/mL;多西环素和阿莫西林等12种抗菌药物的抑菌作用较小,MIC50、MIC90分别为18.53～388.50 μg/mL和30.59～713.42 μg/mL.     

恩诺沙星诱导水生细菌产生耐药性最低浓度选择

渔药多以拌料或直接投入水体的方式给药,药物经动物排泄最终进入土壤和表层水体中,造成药物在表层水体等环境中残留,药物在环境中残留将诱导环境细菌产生耐药性,而且耐药性可能通过食物链、环境或动物和人直接接触进行传递。为了解恩诺沙星在池塘水体中残留对水生细菌的影响,采用琼脂稀释法对水生细菌进行了抗菌药物敏感性试验。结果表明,恩诺沙星诱导水生细菌产生耐药性的最低浓度选择为8μg／mL。     

牛支原体药物敏感性试验

为了解牛支原体的体外药敏试验,以指导临床合理使用抗生素,对临床分离鉴定的3株牛支原体,采用微量稀释法测定其对环丙沙星、恩诺沙星、红霉素和诺氟沙星的最低抑菌浓度(MIC),重复3次,取平均值。结果表明,牛支原体对环丙沙星的MIC抑菌范围为64μg/mL～128μg/mL,对恩诺沙星的MIC值为4μg/mL～8μg/mL,对红霉素的MIC值为2μg/mL～4μg/mL,对诺氟沙星的MIC值在8μg/mL～16μg/mL之间。牛支原体对红霉素的耐药性最低,其次是恩诺沙星、诺氟沙星,对环丙沙星的耐药性最高。     

鸡源大肠杆菌质粒介导的氟喹诺酮类药物耐药基因qnrA的分子检测

对2005年~2007年从豫北地区临床分离的377株鸡源大肠杆菌进行生化鉴定,MIC值测定。被测菌株对氟喹诺酮类（FQs）药物恩诺沙星、环丙沙星和诺氟沙星均呈严重耐药,耐药率分别为94.9%、93.9%、94.9%。选取对恩诺沙星耐药（MIC>32 μg/ml）的235株大肠杆菌进行qnr基因的分子检测,结果显示仅有1株大肠杆菌（MIC=128 μg/ml）呈qnr基因阳性,经测序分析该基因命名为qnrA。     

猪源性链球菌的分离、鉴定和药敏试验

为了找到对猪链球菌病疗效较好的药物,本实验用平皿二倍稀释法,测定了临床分离的27株链球茵的MIC,耐药性监测的结果表明链球菌对所测11种药物有10种产生了不同程度的耐药性,只有盐酸恩诺沙星和阿莫西林对临床所分离的链球菌比较敏感,MIC50分别为0.125μg/mL、4 μg/mL.     

氟苯尼考与多种抗菌药物联合应用对大肠杆菌的体外抑菌试验

为了解氟苯尼考分别与恩诺沙星、TMP和多西环素联合用药的体外抑菌效果,本试验采用倍比稀释法,测定了氟苯尼考、恩诺沙星、TMP和多西环素对大肠杆菌O78的最小抑菌浓度(MIC);采用棋盘法进行恩诺沙星、TMP、多西环素分别与氟苯尼考联合应用对大肠杆菌的药敏试验。结果表明:四种抗菌药物都有较强的抑菌能力,氟苯尼考MIC为4μg/mL,恩诺沙星MIC为0.1μg/mL,TMP的MIC为16μg/mL,多西环素的MIC为4μg/mL。氟苯尼考与恩诺沙星联合表现为无关作用,与TMP联合表现为协同作用,与多西环素联合表现为累加作用。     

营养条件和传代次数对恢复大肠杆菌药物敏感性的影响

为探索恢复细菌对抗菌药物敏感性的方法,文章通过设计单因素试验分别研究了营养条件、传代次数与耐药菌敏感性恢复之间的关系。结果显示,对环丙沙星高度耐药的大肠杆菌菌株[MIC(最小抑菌浓度)=128μg/mL]在稀释8、16和32倍的培养基中传代培养210代后,恢复为敏感菌株(MIC=0.25μg/mL);对环丙沙星高度耐药的大肠杆菌在正常培养基中传代培养210代后,其MIC值为16μg/mL。表明对环丙沙星高度耐药的大肠杆菌在较低的营养条件下可以恢复为敏感菌株,较低的营养条件有利于细菌对药物敏感性的恢复。     

几种抗菌药物对嗜水气单胞菌突变选择窗(MSW)范围的研究

为了测定盐酸恩诺沙星、氟苯尼考和卡那霉素对5株临床分离的嗜水气单胞菌的MSW范围,本研究采用试管双倍稀释法测MIC,平板稀释法测MIC99,以超过1010 CFU接种于药物平板上的方法测MPC,确定了3种抗菌药物对5株临床分离的嗜水气单胞菌的突变选择窗范围.结果表明,卡那霉素和盐酸恩诺沙星对5株嗜水气单胞菌的MIC99相差不大,但MPC之间的差异较大:卡那霉素对4号菌株的MPC明显大于其他几种菌株,恩诺沙星对2号菌株的MPC明显小于其他菌株;氟苯尼考对2号菌株MIC99明显大于其他4种菌株,而MPC值均大于128 μg/mL.因此认为,目前恩诺沙星和氟苯尼考治疗嗜水气单胞菌的给药方案虽可发挥一定的治疗效果,但容易导致嗜水气单胞菌耐药性的产生.     

诺氟沙星诱导水生细菌产生耐药性的最低选择浓度的调查

渔药多以拌料或直接投入水体的方式给药,渔药经动物排泄出体外最终也将进入土壤和表层水体中,从而造成药物在表层水体等生态环境中残留。在生态环境中的药物残留诱导环境细菌产生耐药性,而且耐药性可能通过食物链、环境或者动物和人的直接接触进行传递。为了进一步了解诺氟沙星在池塘水体中的残留对水生细菌的影响,本试验采用琼脂稀释法对水生细菌进行了抗菌药物敏感性试验。结果表明,诺氟沙星诱导水生细菌产生耐药性的最低选择浓度为8μg／mL。     

Bacterial resistance to quinolone antibiotics in Poland

The resistance of 167 pathogenic bacteria of animal origin to quinolones was determined by the disc diffusion method, and by the minimum inhibitory concentration (MIC) test. The highest resistance of Escherichia coli was found to be against nalidixic acid (NA), 49.1% and flumequine (FLU), 38.2%. The sensitivity of the strains were: ciprofloxacin (CIP; 81.8%); enrofloxacin (ENR; 81.8%); norfloxacin (NOR; 80.0%); and pefloxacin (PE; 76.4%). Salmonella spp. showed 100% sensitivity to CIP, ENR, NOR and PE. A high resistance percentage in the cases of: FLU (86.7%); PE (50.0%); and CIP (26.65%) distinguished the Streptococcus spp. The highest percentage sensitivity of Staphylococci was found with three fluoroquinolones: CIP, ENR and NOR, 94.3% each (66 strains). The studies did not indicate that a total cross-resistance might occur between the examined quinolones.     

Susceptibility of bacteria isolated from pigs to tiamulin and enrofloxacin metabolites

Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were tested using selected bacteria with previously defined minimal inhibitory concentrations (MIC). The TIA metabolites tested were: N-deethyl-tiamulin (DTIA), 2beta-hydroxy-tiamulin (2beta-HTIA) and 8alpha-hydroxy-tiamulin (8alpha-HTIA), and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR-N). Bacteria, all of porcine origin, were selected as representatives of bacterial infections (Staphylococcus hyicus and Actinobacillus pleuropneumoniae), zoonotic bacteria (Campylobacter coli) and indicator bacteria (Escherichia coli and enterococci). Furthermore the effects of these compounds were tested on the microbial community of active sludge to test any negative effect on colony forming units (CFU). DTIA had a potency of 12.5-50% of the potency of TIA. 2beta-HTIA and 8alpha-HTIA had potencies less than 1% of the potency of TIA. ENR-N had a potency of 0.75-1.5% of the potency of ENR, while CIP and ENR had similar potencies. Results obtained here indicate that CIP and DTIA could contribute to the selective pressure for upholding antimicrobial resistant bacteria in animals under ENR or TIA treatment. The most potent metabolites CIP and DTIA showed considerable potencies against activated sludge bacteria compared to the parent compounds. EC(50) (microg/ml) for ENR, CIP, TIA and DTIA were 0.018 [95% CI: 0.028-0.149], 0.064 [95% CI: 0.007-0.046], 6.0 [95% CI: 3.6-9.8], and 9.7 [95% CI: 5.8-16.3], respectively. This indicates that the compounds can change the bacterial population in the sludge, and hereby alter the properties of the sludge.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t_1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC_0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr^?1 kg^?1, respectively. The PK parameters of ENR and DNX following IM injection were t_1/2λz 21.10 and 28.41 hr, AUC_0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC_0‐48CPR/AUC_0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC_0‐24/minimum inhibitory concentration (MIC) and maximum concentration (C_max)/MIC ratios for susceptible bacteria, with the MIC₉₀ of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration

To the best of the authors’ knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem–mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43–44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 μg/mL) in freshwater crocodiles, C. siamensis.     

Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows.

OBJECTIVE: To compare pharmacokinetic variables of enrofloxacin (ENR) after IV administration in mice, rats, rabbits, sheep, and cows and to perform allometric analysis of ENR. ANIMALS: 47 mice, 5 rats, 5 rabbits, 5 sheep, and 5 cows. PROCEDURE: Serially obtained plasma samples were assayed for ENR concentration, using high-performance liquid chromatography. In vitro plasma protein binding was determined by ultrafiltration. Plasma ENR concentration versus time curves were fitted by use of nonlinear least-squared regression analysis. Pharmacokinetic variables were correlated further with body weight. RESULTS: In all species studied, the best fit was obtained for a two-compartment open model; ENR half-life ranged from 89 minutes in mice to 169 minutes in cows. Volume of distribution was large in all species studied, with values ranging from 10.5 L/kg in mice to 1.5 L/kg in sheep. Body clearance ranged from 68.1 ml/min/kg for mice to 4.6 ml/min/kg for sheep. Unbound ENR was found to be (mean +/- SD) 58+/-2, 50+/-6, 50+/-2, 31+/-2, and 40+/-3% in plasma of mice, rats, rabbits, sheep, and cows, respectively. The only pharmacokinetic variables that could be correlated with body weight were elimination half-life, clearance, and volume of distribution. Allometric exponents denoting proportionality of half-life, body clearance, and volume of distribution with body weight were 0.06, 0.82, and 0.90, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An allometric approach could provide a suitable method for determining a scale for ENR pharmacokinetics among various mammalian species. This would faciliatate the administration of appropriate doses of ENR to all animals.     

Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits

The purpose of this study was to determine the pharmacokinetics and possible interactions of enrofloxacin (ENR) and flunixin meglumine (FM) in healthy rabbits and in rabbits where endotoxaemia had been induced by administering Escherichia coli lipopolysaccharide (LPS). Six male adult New Zealand White rabbits were used for the study. In Phase I, FM (2.2 mg/kg) and ENR (5 mg/kg) were given simultaneously as a bolus intravenous (IV) injection to each healthy rabbit. After a washout period, Phase II consisted of purified LPS administered as an IV bolus injection, then FM and ENR. LPS produced statistically significant increases in some serum biochemical concentrations. After the drugs were co-administered, the kinetic parameters of FM were not significantly different in healthy compared to endotoxaemic rabbits. It is concluded that ENR and FM could be co-administered to rabbits to treat endotoxaemia as no negative interaction was observed between the pharmacokinetics of both drugs.     

beta-Lactam resistance and beta-lactamases in bacteria of animal origin

beta-Lactams are among the most clinically important antimicrobials in both human and veterinary medicine. Bacterial resistance to beta-lactams has been increasingly observed in bacteria, including those of animal origin. The mechanisms of beta-lactam resistance include inaccessibility of the drugs to their target, target alterations and/or inactivation of the drugs by beta-lactamases. The latter contributes predominantly to beta-lactam resistance in Gram-negative bacteria. A variety of beta-lactamases have been identified in bacteria derived from food-producing and companion animals and may further serve as a reservoir for beta-lactamase-producing bacteria in humans. While this review mainly describes beta-lactamases from animal-derived Escherichia coli and Salmonella spp., beta-lactamases from animal-derived Campylobacter spp., Enterococcus spp., Staphylococcus spp. and other pathogens are also discussed. Of particular concern are the increasingly-isolated plasmid-encoded AmpC-type CMY and extended-spectrum CTX-M beta-lactamases, which mediate acquired resistance to extended-spectrum beta-lactams. The genes encoding these enzymes often coexist with other antimicrobial resistance determinants and can also be associated with transposons/integrons, increasing the potential enrichment of multidrug resistant bacteria by multiple antimicrobial agents as well as dissemination of the resistance determinants among bacterial species. Characterization of beta-lactam-resistant animal-derived bacteria warrants further investigation of the type and distribution of beta-lactamases in bacteria of animal origin and their potential impact on human medicine.