Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink (Neovison vison)

Antimicrobial agents are used extensively off‐label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild‐type E. coli and S. delphini infections in mink.     

Sulfadiazine pharmacokinetics in grass carp (Ctenopharyngodon idellus) receiving oral and intravenous administrations

This study aimed to examine the bioavailability (BA) and pharmacokinetic (PK) characteristics of sulfadiazine (SDZ) in grass carp (Ctenopharyngodon idellus) after oral and intravenous administrations. Blood samples were collected at predetermined time points of 0.083, 0.17, 0.5, 1, 2, 4, 8, 16, 24, 48, 72, and 96 hr (n = 6). The samples were extracted and purified by organic reagents and determined by the ultra‐performance liquid chromatography. The software named 3P97 was used to calculate relevant PK parameters. The results demonstrated that the concentration–time profile of SDZ was best described by a one‐compartmental open model with first‐order absorption after a single oral dose. The main PK parameters of the absorption rate constant (K_α), the absorption half‐life (t_{1/2 Kα}), the elimination rate constant (K_e), the elimination half‐life (t_1/2Ke), and the area under concentration–time profile (AUC_0‐∞) were 0.3 1/h, 2.29 hr, 0.039 1/h, 17.64 hr, and 855.78 mg.h/L, respectively. Following intravenous administration, the concentration–time curve fitted to a two‐compartmental open model without absorption. The primary PK parameters of the distribution rate constant (α), the elimination rate constant (β), the distribution half‐life (t_1/2α), the elimination half‐life (t_1/2β), the apparent distribution volume (V_SS), the total clearance (CL), and AUC_0‐∞ were 9.62 1/hr, 0.039 1/hr, 0.072 hr, 17.71 hr, 0.33 L/kg, 0.013 L h^?1 kg^?1, and 386.23 mg.h/L, respectively. Finally, the BA was calculated to be 22.16%. Overall, this study will provide some fundamental information on PK properties in the development of a new formulation SDZ in the future and is partially beneficial for the appropriate usage of SDZ in aquaculture.     

Soil bacterial community response to sulfadiazine in the soil–root zone

Sulfonamide antibiotics reach soil via manure and adversely affect microbial diversity. Clear effects of these bacteriostatic, growth‐inhibiting antibiotics occur in the presence of a parallel input of microbial activity stimulating manure. Natural hot spots with already increased soil microbial activity are located in the rhizosphere, comprising microorganism such as Pseudomonas with plant growth promoting and pathogenic strains. The hypothesis was therefore that the antibiotic activity of sulfonamides is promoted in the rhizosphere even in the absence of manure, followed by shifts of the natural plant‐specific microbial community structure. This was evaluated by a laboratory experiment with Salix fragilis L. and Zea mays L. After 40 d of incubation, sub‐areas such as non‐rhizosphere soil, rhizosphere soil and plant roots were sampled. Effects on microbial community structure were analyzed using 16S rRNA gene fragment patterns of total bacteria community and Pseudomonas. Selected exoenzymes of N‐, P‐, and C‐cycling were used to test effects on microbial functions. Compared to the factors soil sub‐area and sulfadiazine (SDZ) content, plant species had the largest influence on the bacterial community structure and soil exoenzyme activity pattern. This was also reflected by an up to 1.5‐fold higher acid phosphatase activity in samples from maize‐ compared to willow‐planted soil. We conclude that antibiotic effects on the bacterial community structures are influenced by the antibiotic concentration and root influence.     

水热预处理对猪粪厌氧消化系统中磺胺嘧啶降解的影响

为进一步了解水热预处理对猪粪连续厌氧消化过程中磺胺嘧啶（sulfadiazine, SDZ）降解机制的影响,以及对厌氧消化系统性能的影响效果。该研究以猪粪为对象,对比研究了水热预处理对厌氧发酵模式下SDZ的降解变化规律与途径及其对猪粪产气性能的影响。研究结果表明：水热预处理（150 ℃）使中温连续厌氧反应器中的SDZ的综合去除率显著提升（P <0.05）,由40.5%～58.5%提高到54.4%～75.2%;并且通过中间降解产物推测SDZ的生物降解途径主要包括SDZ水解、羟基化、硫脱氧、氨基氧化、嘧啶环裂解等;在厌氧消化性能方面,水热预处理使稳定运行后反应器的日产沼气量提高了约34.05%（P <0.05）。此外,对反应器中微生物群落分析后,发现Syntrophomonas、Sedimentibacter与SDZ的降解高度相关,并且经过水热预处理后Sedimentibacter的相对丰度较未水热预处理显著提升。因此,水热预处理耦合厌氧消化工艺具有同步提高SDZ降解和厌氧消化性能的作用,有助于进一步提高沼液的生态安全性。     

三种农用抗生素降解真菌的筛选及其降解性能

为了从重金属污染的土壤中分离筛选出能降解土霉素、诺氟沙星、磺胺二甲嘧啶的真菌菌株,利用抗生素作为唯一碳源进行抗生素降解真菌富集驯化培养,分离纯化耐受真菌,将纯化后的菌株回接到以抗生素作为唯一碳源的液体培养基中,运用高效液相色谱法（HPLC）及紫外分光光度法对各菌株抗生素降解能力进行检测,并通过菌落形态学特征、ITS序列和系统发育树对菌株进行分子鉴定。筛选到4株抗生素降解真菌KS248、KS256、KS257、KS272,分别鉴定为轮状镰刀菌（Fusarium verticillioides）、腐皮镰刀菌（Fusarium solani）、聚多曲霉（Aspergillus sydowii）、微紫青霉（Penicillium janthinellum）。其中,菌株KS248、KS256、KS257具有土霉素、诺氟沙星、磺胺二甲嘧啶降解能力;菌株KS272具有土霉素、诺氟沙星降解能力。在抗生素初始浓度1500 μg·L^-1、30℃、150 r·min^-1条件下避光培养7 d后,菌株KS272降解土霉素、诺氟沙星能力最强,降解率分别达到40.29%、10.59%,菌株KS256降解磺胺二甲嘧啶能力最强,降解率达到18.53%。筛选出的菌株均具有2种及以上抗生素降解能力,对抗生素的降解率从高到低依次为土霉素、诺氟沙星、磺胺二甲嘧啶,且随着抗生素浓度增加,菌株对各抗生素降解能力有不同程度的削弱。     

利用表面等离子共振法检测牛乳中磺胺嘧啶

利用表面等离子体共振(surface plasmon resonance,SPR)技术检测牛乳中的磺胺嘧啶。将牛血清白蛋白偶联的磺胺类药物广谱抗原作为传感芯片特异识别探针结合到生物芯片表面,通过免疫竞争抑制法原理结合SPR技术检测牛乳中的磺胺嘧啶。建立标准曲线,检测磺胺嘧啶的最低检测限为3.41 ng/mL,牛乳中加标准品的回收率为71％～120％,所采用的SPR方法对于检测牛乳中的磺胺嘧啶具有较高的灵敏度和准确性。     

磺胺嘧啶在黑土及其不同粒径组分中的吸附行为研究

采用批平衡吸附试验法,研究了磺胺嘧啶在黑土及其不同粒径中的吸附行为。结果表明,磺胺嘧啶的吸附不同程度地偏离线性模型,但均可用Freundlich模型和Langmuir模型进行良好地线性拟合。黑土（〈0.2mm）及其不同粒径（粘粒：〈0.002mm、粉粒：0.002~0.02mm、砂粒：0.02~0.2mm）的Freundlich容量因子Kf值分别为29.6、53.1、32.9L.kg-1和21.6L.kg-1,说明磺胺嘧啶在黑土及其不同粒径中的吸附行为存在差异。将吸附参数Kf进行碳标化处理后,Koc值除粉粒外,其他基本一致。随着溶液pH的持续增加（1.0~10.0）,黑土及其不同粒径中的磺胺嘧啶的吸附参数lgKf呈现先急剧降低然后稍微回升的趋势,由此推测,阳离子交换作用可能是磺胺嘧啶土壤吸附的重要机制。过氧化氢处理去除土壤有机质后,黑土的Kd值从1.92L.kg-1降为1.22L.kg-1,磺胺嘧啶的吸附量由16.5mg.kg-1降低到11.2mg.kg-1,说明有机质含量也是影响磺胺嘧啶吸附行为的重要因素。     

高效液相色谱同时检测鱼肉组织中4种磺胺与甲氧苄啶的残留量

建立了同时测定鱼肉组织中4种磺胺(磺胺嘧啶、磺胺甲基嘧啶、磺胺二甲基嘧啶、磺胺甲恶唑)和甲氧苄啶残留量的高效液相色谱法.鱼肉组织用乙腈提取后经乙腈饱和的正己烷去脂,过HLB柱净化,甲醇洗脱,减压浓缩蒸干,流动相(乙腈+1%乙酸,体积比为10∶90)定容,用带DAD检测器的高效液相色谱仪在272 nm波长下检测,流动相采用梯度洗脱.结果显示:4种磺胺和甲氧苄啶分别在0025～10 μg·mL-1和005～20 μg·mL-1范围内呈良好线性关系,相关系数(r)为0999;4种磺胺和甲氧苄啶分别在002、010和020 mg·kg-1和004、020和040mg·kg-1 3个浓度水平下的添加回收率为752%～979%,变异系数为28%～100%(n＝6);根据3倍信噪比计算,磺胺嘧啶、磺胺甲基嘧啶、磺胺二甲基嘧啶、磺胺甲恶唑和甲氧苄啶的最低检测限分别为0006、0007、0008、0008和0019mg·kg-1.     

HPLC法测定复方磺胺嘧啶钠注射液的含量

为建立兽药复方磺胺嘧啶钠注射液含量测定的高效液相色谱测定法。采用流动相为0.1%的磷酸溶液-乙腈(85:15,V∶V),色谱柱为C18柱,柱温为40℃,流速为1.0 mL/min,检测波长为240 nm。采用外标法进行定量。磺胺嘧啶钠的线性范围为12.5～200μg/mL,线性方程为Y=44.873X+11.999,r~2=1.000;甲氧苄啶的线性范围为2.5～40μg/mL,线性方程为Y=62.288X+4.0826,r~2=1.000,方法的线性关系良好,添加回收率均大于98%,RSD均小于2%。结果显示该方法简单、精确、可操作,可以用于测量复方磺胺嘧啶钠注射液中磺胺嘧啶钠与甲氧苄啶的含量。     

磺胺嘧啶在土壤中的降解与迁移研究

为了较为全面地了解兽药磺胺嘧啶在土壤环境中的降解性和迁移性,通过室内模拟降解试验和动态土柱淋溶试验,研究了磺胺嘧啶在土壤中的降解和迁移行为。结果表明,在试验条件下,磺胺嘧啶在土壤中的降解能力很弱。磺胺嘧啶在土壤中有一定的淋溶向下迁移性,不同土壤间迁移状况差异较大。砂土中磺胺嘧啶具有较强的迁移能力,经淋溶后渗出40cm土柱的磺胺嘧啶为加药量的70.16%,而其在壤土和粘土柱中的渗出率分别为39.66%和51.12%。磺胺嘧啶在3种供试土壤中的淋溶向下迁移能力为：砂土〉粘土〉壤土。磺胺嘧啶在土壤中的淋溶向下迁移能力与土壤性质密切相关,土壤质地和有机质含量是影响磺胺嘧啶在土壤中淋溶向下迁移能力的重要因素。