近年来，碳青霉烯耐药肠杆菌成为了一个威胁临床抗生素治疗的问题。肠杆菌属细菌作为腐生多宿主细菌，在环境、畜禽和人之间广泛存在，调查畜禽养殖生产过程中的碳青霉烯耐药肠杆菌属细菌，对预防和遏制肠杆菌属细菌碳青霉烯类耐药具有重要意义。

本研究从中国某养鸭场的鸭肠道与环境样本中，分离出携带bla_IMI的碳青霉烯类和黏菌素耐药肠杆菌属细菌。药敏试验显示，四株bla_IMI阳性肠杆菌属细菌分离株对碳青霉烯和黏菌素具有耐药性。PCR和Sanger测序证明了在不同ST型的菌株中检测到了三种bla_IMI亚型。全基因组测序证明bla_IMI基因存在于这些菌株的染色体或质粒中。接合转移实验证明了携带bla_IMI的质粒具有水平传播的能力。我们运用比较分析手段对其分子进化特征进行了研究，发现两株bla_IMI-16阳性阿氏肠杆菌之间具有高度相似的基因环境，但有着较远的亲缘关系，这提示了bla_IMI-16水平传播的可能。此外，携带bla_IMI-16的质粒是IncFⅠⅠ(Yp)质粒，该型质粒能够使宿主菌具备生长的竞争性优势。在该质粒上，bla_IMI-16的上下游鉴定出大量的可移动遗传元件（MGEs）序列，以IS1081、Tn903和ISE居多。本研究中的bla_IMI阳性肠杆菌属细菌中还携带有毒力基因，有助于增强菌株致病性。

综上所述，我们发现了在中国某鸭场内的肠杆菌属细菌中，bla_IMI由IncFⅠⅠ(Yp)质粒携带并促进其传播，从而导致了细菌碳青霉烯耐药性的传播。可移动遗传元件在水平传播中发挥着重要作用。对于bla_IMI基因的研究较少，此前，从未在中国大陆的养殖源细菌中发现，也未见有bla_IMI-16基因在中国大陆被鉴定的报道。我们的研究为不同亚型bla_IMI基因在中国的传播提供了证据，并为研究bla_IMI阳性耐药肠杆菌属细菌提供了参考数据。本研究强调：我们仍需要定期监测动物饲养过程中的bla_IMI阳性肠杆菌属细菌，以预防及遏制日益严重的碳青霉烯类药物耐药性传播的威胁。

抗生素耐药性已成为威胁人类健康的全球性问题。抗生素被广泛应用于肉鸡养殖从而影响它们的肠道微生物组和耐药组。为了更好地了解对农场动物持续性给药是如何改变微生物生态的变化，我们采用宏基因组的方法，研究脉冲式抗生素给药对肉鸡粪便微生物群、耐药基因（ARGs）及其宿主的影响。肉鸡分别接受三次连续五天的阿莫西林、金霉素、氟苯尼考单独给药和三种药的联合给药。结果显示，给药氟苯尼考能显著增加耐药基因floR和mcr-1的丰度，而给药阿莫西林则显著增加编码AcrAB-tolC外排泵的相关基因，如marA、soxS、sdiA、rob、evgS and phoP。这三种抗生素给药都显著增加微生物群中变形菌门的丰度。我们推测，耐药基因宿主埃希菌属丰度的上升，主要是由于在脉冲式抗生素给药下，其携带了β-内酰胺类、氯霉素和四环素耐药基因。这些结果表明，脉冲式阿莫西林、金霉素、氟苯尼考或三种药物的联合给药都能显著提高微生物群中变形菌门的丰度，而且会增加特定耐药基因的丰度。耐药基因大类主要由多重耐药基因组成，并且在抗生素处理的组别中，多重耐药基因的丰度与耐药基因总丰度具有很强的相关性。本研究对经脉冲式抗生素给药的鸡的粪便微生物群和耐药组的改变提供了全面的见解。

The objective of this study was to verify the supposition that efflux might be involved in the drug resistance of Riemerella anatipestifer isolates. Two broad-spectrum efflux pump inhibitors, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and Phe-Arg-β-naphthylamide (PAβN), on the contribution of minimum inhibitory concentrations of amikacin, streptomycin, chloramphenicol, tetracycline, ceftriaxone, ceftazidime, nalidixic acid, levofloxacin, enrofloxacin, as well as ciprofloxacin against 69 clinical R. anatipestifer isolates were investigated. We first reported that the two efflux pump inhibitors could restore the antimicrobial susceptibility of R. anatipestifer isolates. It is suggested that active efflux system is possible to be linked with the development of resistance in R. anatipestifer isolates.

Contamination of deoxynivalenol (DON) in grains is common worldwide and pigs are particularly susceptible to this mycotoxin. The distribution of DON in porcine tissues following intravenous administration was investigated in this study. Fifteen pigs were randomly divided into three groups. Animals in groups A and B were administrated with DON at the dose of 250 and 750 μg kg–1 body weight, respectively, while group C served as blank control. Plasma, bile and 27 tissues were collected at 30 min post-administration. DON concentrations in all samples were tested using high-performance liquid chromatography- tandem mass spectrometry (HPLC-MS/MS). To observe the distribution of DON in tissues, these samples were further subjected to the immunohistochemical analyses. Totally, the bile and 13 tissues were sampled for DON-based detection, including kidney, mesenteric lymph nodes, muscle, stomach, jejunum, colon, plasma, spleen, rectum, cecum, liver, ileum, and duodenum. No significant difference was observed for the concentrations of DON in duodenum, ileum and liver samples between groups A and B; while the DON concentrations in cecum and rectum of group B were significantly higher (P-value <0.05) than those in group A. In addition, the DON concentrations in stomach, jejunum, colon, mesenteric lymph nodes, muscle, kidney, spleen, bile, and plasma of group B were remarkably higher than those of group A (P-value<0.01). Levels of DON in other 14 tissues including medulla oblongata, midbrain, diencephalon, pons, tip and tongue body, tongue, soft palate, tonsils, pharyngeal mucosa, oral buccal mucosa, thymus, thyroid, esophagus and adrenal gland were all below the limit of detection. The results of immunohistochemistry showed that 11 tissue samples (medullaoblongata, tonsil, adrenal medulla, thyroid gland, thyroid, stomach, duodenum, jejunum, kidney, spleen, and mesenteric lymph nodes) were positive and DON was mainly distributed around blood vessels in these tissues. Therefore, we believed that concentrations of DON in tissues differ when pigs are in exposure to various dosages and DON causes lesions in many pig tissues.

The purpose of the study was to investigate the pharmacokinetics of cefquinome in plasma and milk samples of lactating Chinese Holstein following a single intramammary administration into one quarter at the dose of 75 mg. Residue depletion of cefquinome in milk administrated at one quarter following three consecutive infusions at the same dose were also carried out. Cefquinome concentrations in plasma and milk were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental analysis was used to obtain the pharmacokinetic parameters of cefquinome. Following the single treatment, cefquinome wasn’t detected in any of the plasma samples. The concentration of cefquinome in milk reached peaked values (Cmax) of (599.00±322.00) μg mL-1 at 2 h after administration (Tmax), elimination half-life (t1/2λz) was (4.63±0.26) h, area under the concentration-time curve (AUC0-∞) was (4 890.19±1 906.98) μg mL-1 h, and mean residence time (MRT) was (6.03±2.27) h. In residue depletion study, cefquinome concentrations in 5 out of 6 milk samples at 72 h were lower than the maximum residue limit fixed by the European regulatory agency (20 μg kg-1 for cefquinome) and cefquinome still could be detected in milk of treated quarters at 120 h post-treatment. The maximum concentration (Cmax) of cefquinome in milk from treated quarters was (486.50±262.92) μg mL-1 and arrived at 6 h after administration (Tmax), elimination half-life (t1/2λz) was (6.30±0.76) h, area under the concentration-time curve (AUC0-∞) was (44747.79±11434.43) μg mL-1 h, and mean residence time (MRT) was (10.09±1.40) h. This study showed that cefquinome has the feature of poor penetration into blood and was eliminated quickly from milk in lactating cows after intramammary administration.

Pharmacokinetics of cyadox (CYX) and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox (BDCYX), cyadox-1-monoxide (CYX-1-O) and quinoxaline-2-carboxylic acid (QCA), three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox (CYX) was administered to 8 healthy cross-bread swine intravenously (i.v.) and orally (p.o.) at a dosage of 1 mg kg-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve (AUC0- ) were (0.38±0.03) μg mL-1 h (CYX), (0.018±0.002) μg mL-1 h (BDCYX) and (0.17±0.02) μg mL-1 h (CYX-1-O), respectively. The terminal elimination half-lives (t1/2lz) were determined to be (0.93±0.07) h (CYX), (1.45±0.04) h (BDCYX), and (0.92±0.04) h (CYX-1-O), respectively. Steady-state distribution volume (Vss) of (2.14±0.11) L kg-1 and total body clearance (CL) of (2.84±0.19) L h-1 kg-1 were determined for CYX after i.v. dosing. The bioavailability (F) of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations (Cmax) of (1.08±0.06) μg mL-1 (CYX), (0.0068± 0.0004) μg mL-1 (BDCYX) and (0.25±0.03) μg mL-1 (CYX-1-O) were observed at Tmax of 0.033 h (CYX), 1 h (BDCYX) and 0.033 h (CYX-1-O), respectively. The main pharmacokinetic parameters after p.o. administration were as follows: AUC0- were (0.42±0.04) μg mL-1 h (CYX), (1.38±0.14) μg mL-1 h (BDCYX), (0.59±0.02) μg mL-1 h (CYX-1-O) and (1.48±0.09) μg mL-1 h (QCA), respectively. t1/2lz were (4.77±0.33) h (CYX), (5.77±0.56) h (BDCYX), (4.12±0.28) h (CYX-1-O), and (8.51±0.39) h (QCA), respectively. After p.o. administration, Cmaxs of (0.033±0.002) μg mL-1 (CYX), (0.22±0.03) μg mL-1 (BDCYX), (0.089±0.005) μg mL-1 (CYX-1-O), and (0.17± 0.01) μg mL-1 (QCA) were observed at Tmax of (7.38±0.33) h (CYX), (7.25±0.31) h (BDCYX), (7.38±0.33) h (CYX-1-O), and (7.25±0.31) h (QCA), respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve (AUC0- )of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t1/2lz) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.

An accurate and precise method for the determination of tulathromycin in swine plasma was developed and validated. Plasma samples were analyzed by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) using electrospray ionization (ESI). Tulathromycin was extracted from plasma by precipitation with acetonitrile and separated using a Phenomenex Luna 5 μm C18 column (150 mm×2.0 mm) at a flow rate of 0.25 mL min-1. Solvent A consisted of 0.002 mol L-1 ammonium acetate and formic acid (999:1, v/v), and solvent B was acetonitrile. The mass spectrometer was operated in the selected-ion mode with atmospheric pressure chemical ionization to monitor the respective MH+ ions, namely, m/z 577.3 for tulathromycin and m/z 679.3 for the internal standard roxithromycin. The calibration curves were linear in a dynamic range of 2.0-500 ng mL-1 on the column. The accuracy was ranged from 95.25 to 109.75%, and the precision was ranged from 2.81 to 7.72%. The recoveries measured at 3 concentration levels (20, 250, and 500 ng mL-1) were higher than 98%. The method described above is efficient, and has the required accuracy and precision for rapid determination of tulathromycin in plasma. The method was applied to study the pharmacokinetics of tulathromycin in swine, and tulathromycin demonstrated a rapid absorption, wide distribution, and slow elimination after intramuscular administration.