Antibiotic resistance of motile aeromonads in indoor catfish and eel farms in the southern part of The Netherlands

The prevalence and degree of antibiotic resistance in catfish and eel farms in the southern part of The Netherlands was examined using motile aeromonads as indicator bacteria. A total of 29 water samples were collected, originating from six catfish farms, one catfish hatchery and three eel farms, and were plated on an Aeromonas-selective agar with and without antibiotics. From each plate, one colony was screened for presumptive motile aeromonads and tested for antibiotic susceptibility. The prevalence of resistance was as follows: ampicillin and oxytetracycline 100%; sulfamethoxazole 24%; trimethoprim 3%; and ciprofloxacin and chloramphenicol 0%. The majority of samples showed a high degree of oxytetracycline resistance, implicating fish farms as a major reservoir of oxytetracycline resistance genes. This reservoir might form a risk for human health and has major consequences for the effectiveness of this antibiotic in the treatment of infectious diseases in fish.     

土霉素片溶出度测定方法研究

目的:建立土霉素片溶出度的测定方法。方法:在检测波长271nm下用紫外分光光度法测定土霉素含量;以0.01mol·L-1盐酸溶液作溶剂,选用桨法测定土霉素片溶出度。结果:土霉素检测浓度线性范围为4～32IU·mL-(1r=0.9999)。平均回收率为100.1%(RSD=0.65%);45min时样品溶出度均在75%以上。结论:所建立方法可用于土霉素片溶出度测定。     

Exposure of a Tropical Soil to MG/KG of Oxytetracycline Elicits Hormetic Responses in the Catabolic Activities of Its Microbial Community

Many farmers in developing countries protect their crops with oxytetracycline and fertilize their farmlands with manure from animals that received this drug as growth promoter. In this study, a tropical soil was exposed to 0.1 mg kg(-1), 1 mg kg(-1), and 10 mg kg(-1) of oxytetracycline for 22 days to evaluate whether this antibiotic alters the capacity of a soil microbial community to metabolize 31 carbon sources. The communities exposed to 1 and 10 mg kg(-1) of oxytetracycline exhibited reduced catabolic activities for 3 and 6 substrates, respectively. In contrast, the communities exposed to 0.1 mg kg(-1) of oxytetracycline showed higher catabolic activities than the controls and the other two treatments for 19 substrates. These data reveal a hormetic response at the community level not previously described for soil bacteria and oxytetracycline.     

The Effects of Antibiotics and Steroids on the Carriage of Vaginal Bacteria into the Uterus During Insertion of Intra-uterine Monofilaments in the Guinea-pig

Abstract— The effects of systemic norethisterone acetate and oxytetracycline hydrochloride on the levels of vaginal microorganisms found in the uterus after the insertion of transcervical, intra-uterine monofilaments in the guinea-pig were determined. The results indicated that bacteria were transferred to the uterus from the vagina during the insertion process and, in the presence of an intra-uterine substrate, persisted for up to 6 months. Daily treatment with norethisterone acetate or oxytetracycline hydrochloride whilst the monofilament was in-situ failed to reduce the bacterial numbers in the uterus. Similarly, daily treatment with oxytetracycline hydrochloride for the 5 days before monofilament insertion had no effect on these bacteria.     

液相色谱-质谱联用法测定牛奶中4种四环素类药物残留量

目的建立牛奶样品中四环素、土霉素、金霉素、美他环素药物残留量的测定方法 ,进一步探讨四环素类药物的电喷雾质谱规律。方法生物样品经固相萃取后 ,采用HypersilBDS柱分离 ,以乙腈 水 甲酸 (体积比 37 5∶6 2 5∶1 2 )作为流动相 ,采用电喷雾离子源 ,以正离子检测方式进行一级、二级质谱分析。结果牛奶中四环素、土霉素及美他环素的检测限可达 0 0 5 μg/mL,金霉素的检测限可达 0 1 μg/mL。四环素、土霉素及美他环素的浓度在 0 1～ 5 0 μg/mL内 ,金霉素浓度在0 2～ 1 0 0 μg/mL内均呈线性。结论该方法专属性强 ,灵敏度高 ,适用于牛奶或其他生物样品中四环素类药物测定     

海葵来源真菌Cochliobolus lunatus（TA26-46）对土霉素生物转化的研究

目的 研究海葵来源真菌Cochliobolus lunatus (TA26-46)对土霉素的生物转化作用。方法 通过在察氏固体培养基平板中添加土霉素,利用海洋真菌体内特殊的转化酶系统对土霉素进行生物转化;利用HPLC-DAD进行转化产物的追踪,并运用硅胶柱层析和半制备型HPLC等分离纯化转化产物,利用核磁、质谱等现代波谱分析方法对转化产物进行结构鉴定,并测试转化产物的抗菌活性。 结果 海洋真菌C. lunatus (TA26-46)对土霉素(1)产生了生物转化作用,从发酵物中分离鉴定得到2个土霉素的降解产物hemi-cyclines A 和B (2和3)。抗菌活性测试结果表明,降解产物未显示抗菌活性。结论 通过生物学方法,利用海洋真菌C. lunatus (TA26-46)成功对四环类抗生素土霉素进行了生物转化,获得了无抗菌活性的降解产物,为解决环境中的抗生素污染问题提供了借鉴。     

Comparative pharmacokinetics of doxycycline and oxytetracycline in patients with hyperlipidemia

This study examines the pharmacokinetics of lipophilic drug doxycycline (Vibramycin) and water-soluble antibiotic oxytetracycline hydrochloride (Oxyterracyna) in patients with hyperlipidemia type IIa and type IV according to Fredrickson. Antibiotics were administered orally as a single dose and determined in plasma by a fluorimetric method. The calculations were performed by aid of a computer. Increased concentrations of doxycycline were found; they were higher in type IIa, as compared with type IV. Area under the curve (AUC) and peak concentrations as well as rate constant for elimination in subjects with type IV were significantly elevated; volumes of distribution and total body clearance were markedly diminished. Decreased concentrations of oxytetracycline, area under the curve, peak concentration and rate constant for elimination were observed in patients with type IV. In both types of hyperlipidemia volume of distribution was increased and half-life in patients with type IV was significantly prolonged. The findings show that hyperlipidemia can be an important factor of drug action. Alterations of pharmacokinetics of lipophilic doxycycline and hydrophilic oxytetracycline were contrasting.     

Bioavailability and dissolution of different formulations of oxytetracycline preparations.

1 The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of five different preparations of the antibiotic. None of these preparations had been studied previously. 2 There was a statistically significant correlation between the time required for 50% dissolution at pH 2 and biological availability, as assessed by the peak plasma level or the area under the plasma concentration-time curve. 3 The mean bioavailability of oxytetracycline was greatest with preparations of the hydrochloride, and with film-coated tablets of the dihydrate. In contrast, sugar-coated tablets of oxytetracycline dihydrate were associated with poorer dissolution characteristics and reduced biological availability.     

Comparative pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline in rainbow trout (Oncorhynchus mykiss).

1. The pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline were studied in rainbow trout at a water temperature of 16 degrees C after intravascular (10 and 20 mg/kg, respectively) and oral (75 mg/kg) dosing. 2. The pharmacokinetics were best described by a two-compartment open model giving distribution half-lives of 0.31 h and 1.53 h, and elimination half-lives of 69.7 h and 60.3 h for oxolinic acid and oxytetracycline, respectively. The respective volumes of distribution (Vdarea) were 1.94 l/kg and 1.34 l/kg. 3. The apparent oral bioavailability for oxolinic acid and oxytetracycline was 13.6% and 5.6%. 4. The plasma protein binding was 27% for oxolinic acid and 55% for oxytetracycline. 5. Both drugs were well tolerated, the acute oral toxicities (LD50) exceeding 4000 mg/kg.     

浊度法测定土霉素原料药及其片剂的效价

目的:建立测定土霉素原料药及其片剂效价的浊度法。方法:采用浊度法,试验菌为金黄色葡萄球菌,加菌量为1.0%～1.5%(V/V),培养温度为37℃,培养时间为4h左右;同时与管碟法比较效价测定结果。结果:土霉素检测浓度的线性范围为0.05～0.4IU·mL-1,原料药平均回收率为99.59%(RSD=2.0%),片剂平均回收率为99.51%(RSD=1.91%);与管碟法比较含量无显著性差异。结论:本方法灵敏、快速、影响因素较少,可用于测定土霉素原料药及其片剂的效价。     

Validation of a single liquid chromatography-tandem mass spectrometry approach for oxytetracycline determination in bull plasma,seminal plasma and urine

Oxytetracycline is a broad-spectrum antibiotic, which inhibits protein synthesis and is generally used for the treatment of pneumonia, shipping fever, leptospirosis and wound infections in cattle and swine. The present work proposes a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for oxytetracycline quantification in bull plasma, seminal plasma and urine, requiring limited sample treatment before analysis. Extraction with trichloroacetic acid followed by dilution of the supernatant in mobile phase proved to be effective in all three matrices, allowing to rapidly process large batches of samples. Sharp and symmetrical peak shape was obtained using a BEH C18 reversed-phase column in a chromatographic run of just 3.5 min. The mass spectrometer operated in positive electrospray ionization mode and monitored specific transitions for oxytetracycline (461.1 → 425.8) and the internal standard demeclocycline (465.0 → 447.6). The method was validated over concentration ranges suitable for field concentrations of oxytetracycline found in each matrix, showing good linearity during each day of testing (R² always >0.99), as also confirmed by analysis of variance (ANOVA) and lack-of-fit tests. Excellent accuracy and precision were demonstrated by calculated bias always within ±15% and CV% below 10% at all quality control (QC) levels in the three matrices. Matrix effect and recovery were investigated for both analytes, which showed consistent and comparable behaviour in each matrix. To our knowledge, this is the first validated approach for mass spectrometric determination of oxytetracycline in seminal plasma and urine. The method was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to assess the oxytetracycline concentration–time profile in plasma, seminal plasma and urine.     

In vitro toxicity of antimicrobials on RTG-2 and RTL-W1 fish cell lines

This study proposed a battery of endpoints based on in vitro fish cell lines. Two fish cell lines and four toxicity endpoints are considered. The tetracycline (TC), oxytetracycline (OTC), sulfachlorpyridazine (SCP), and septrin(?) (ST) were selected as model antimicrobials and chlorpyrifos as positive control. EROD was induced by septrin(?) (formulation containing sulfamethoxazole and trimethoprim) at concentrations higher than 20mg/L, but inhibited by tetracycline, oxytetracycline and chlorpyrifos. Dose dependent inhibition responses were observed for β-galactosidase (β-Gal) activity in cells exposed to septrin(?), tetracycline or oxytetracycline. The EROD EC50s ranged between 2.29×10(-2)mg/L (chlorpyrifos) and 167.63mg/L (tetracycline). The β-Gal EC50s ranged between 22.1 (septrin(?)) and 84.59mg/L (tetracycline). Data suggest that in vitro testing using a battery of endpoints can be a cost-effective solution for screening the toxicity of antimicrobials on fish. The absence of in vitro effects at concentrations well above those expected/measured in the environment may replace the need for conducting acute lethality tests on fish.     

Comparative pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline in rainbow trout (Oncorhynchus mykiss)

1. The pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline were studied in rainbow trout at a water temperature of 16°C after intravascular (10 and 20?mg/kg, respectively) and oral (75?mg/kg) dosing.

2. The pharmacokinetics were best described by a two-compartment open model giving distribution half-lives of 0˙31?h and 1˙53?h, and elimination half-lives of 69˙7?h and 60˙3?h for oxolinic acid and oxytetracycline, respectively. The respective volumes of distribution (V_darea) were 1˙94 1/kg and 1˙34 1/kg.

3. The apparent oral bioavailabiiity for oxolinic acid and oxytetracycline was 13˙6% and 5˙6%.

4. The plasma protein binding was 27% for oxolinic acid and 55% for oxytetracycline.

5. Both drugs were well tolerated, the acute oral toxicities (LD₅₀) exceeding 4000?mg/kg.     

On the influence of a special preparation of oxytetracycline and sodiumbituminosulfonates on amount and composition of skin surface lipids in acne vulgaris (author's transl)]

Two groups of 27 and 23 patients with acne vulgaris were first treated for a period of one week with 1 g oxytetracycline a day p.o. In a second treatment period of 6 weeks the first group received 100 mg oxytetracycline a day p.o. and the second group a combination of 100 mg oxytetracycline and 1.2 g sodiumbituminosulfonates a day p.o. In the third treatment period, similarly continued for 6 weeks, the method was reversed. Gastric juice-insoluble preparations were used for the investigation. All criteria for a double-blind study were considered. Amount and composition of the skin surface lipids were analysed before beginning the treatment, at the end of the 2nd and at the end of the 3rd treatment period. The combination of both agents in gastric juice-insoluble preparations suppresses to a great extent the known effects brought about by the substances separately, namely the reduction in free fatty acids and the decrease in the skin surface lipids. The findings also show that the reduction of the free fatty acids was in a limited time observed only in patients treated with 100 mg oxytetracycline a day p.o. if they had been treated in the beginning of this therapy with a higher dosage of tetracycline.     

The action of colloidal silicon dioxide as a glidant for lactose, paracetamol, oxytetracycline and their mixtures.

Anomalies are observed in some of the physical and mechanical properties of mixtures of lactose, paracetamol and oxytetracycline when small amounts of colloidal silicon dioxide are added to them. Owing to its differing propensities to coat the particles of the host powders, the silicon dioxide acts as a glidant for the lactose and paracetamol, but as an antiglidant for the oxytetracycline.     

Bioactivity of some chemotherapeutic agents in selected polyethylene glycol ointment bases

Six different chemotherapeutic agents were individually incorporated in each of fourteen selected polyethylene glycol ointment bases, and their bioactivities were assessed using different diffusion techniques. The prepared medicated ointments were evaluated for drug release using the standard microbiological agar cup diffusion, the long period method and the short period method, as well as dialysis through artificial kidney membrane. On the basis of consistency, stability and diffusion results, formulation 11 was the most suitable base for ampicillin, formulation 14 for oxytetracycline HCl, formulation 10 and 9 for neomycin sulphate, and preparation 10 for chloramphenicol. On the basis of the results of drug release, it was evident that formulation 3 was the best for ampicillin and chloramphenicol, formulation 2 for erythromycin, formulation 4 for neomycin sulphate, formulation 12 for sulphadimidine, and formulation 14 for oxytetracycline HCl.     

土霉素及其盐酸盐的热特征

用差示扫描量热法 (DSC)和导数热重法 (DTG)测定土霉素及其盐酸盐的热特征 ,包括熔点、多晶型、水分、分解点温度和热焓值。结果显示土霉素与对照品热特征一致。盐酸土霉素熔融分解过程无转晶变化。     

膜分离法回收土霉素结晶母液中的土霉素

土霉素结晶母液经超滤膜预处理后 ,通过反渗透膜所得浓缩液 ,再经超滤膜处理后 ,15 %氨水调p H值从土霉素结晶母液回收土霉素 ,得到的土霉素纯度 82 .9% ,效价 771u/ mg,回收率 6 2 %。此结晶母液为二次母液 ,与车间冲洗水等混合后可较容易地进行生物降解     

The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.     

The disposition of four tetracyclines in normal subjects

Summary The disposition of minocycline, tetracycline, doxycycline and oxytetracycline was investigated in four male volunteers after multiple dosing. Values for half life, renal clearance and volume of distribution were calculated and corrected for plasma protein binding. Tetracycline and oxytetracycline have a much larger volume of distribution than minocycline and doxycycline but similar half lives. They give higher tissue levels for equivalent plasma levels. Since their cost per unit dose is much lower they should be the tetracyclines of first choice.