Ecotoxicological effects of human and veterinary antibiotics on water flea (Daphnia magna)

In the present study, we assessed the ecotoxicological effects of selected human and veterinary antibiotics to D. magna. Ecological risk assessment was done by calculating the risk quotients (RQs) of the antibiotics to the species. Results showed that enrofloxacin, a veterinary fluoroquinolone antibiotic, was the most toxic against D. magna with a 48 h EC₅₀ value of 28.59 mg/l. The binary mixture of fluoroquinolones was also more toxic to the species than binary mixtures of macrolides. Fecundity in organisms in negative control was higher than fecundity in organisms exposed to environmentally relevant concentrations of the four antibiotics. Enrofloxacin also has a moderate risk to the species with RQ values of 0.199 and 0.416 in surface waters and wastewaters, respectively. Antibiotics pose a greater ecological risk when present in mixtures in the aquatic environment. Environmental standards for pharmaceuticals should incorporate mixture toxicity data to ensure accurate protection of non-target organisms in polluted environments.     

A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae

The toxicity of fourteen widely used human pharmaceuticals was determined using the Frog Embryo Teratogenesis Assay–Xenopus (FETAX). Stage 9 Xenopus blastulae were exposed for 96 h to single concentrations of commonly prescribed selective serotonin reuptake inhibitors (SSRIs), statin blood lipid regulators, non-steroidal anti-inflammatories, antibiotics, a stimulant, and an anti-epileptic. Toxicity, teratogenicity, minimum concentration to inhibit growth, and types and severity of associated malformations were determined. EC₁₀s ranged from 3.0 mg/l to >100 mg/l and LC₁₀s ranged from 3.6 mg/l to >100 mg/l. Toxicity varied between and within compound class of pharmaceutical. The fluoroquinolones, stimulants, anti-epileptics, and antibiotics tested were determined to be nontoxic and non-teratogenic at singular, water-soluble concentrations. The hazard quotients (HQ) for the pharmaceuticals ranged from 6.10 × 10⁻⁷ to 1.6 × 10⁻⁴, all of which are orders of magnitude below EPA’s levels for concern for harm to aquatic animals. Thus, based on the data from the present study, concentrations of individual pharmaceuticals currently detected in surface water are far below concentrations of effective and lethal concentrations.     

HPLC residues of enrofloxacin and ciprofloxacin in eggs of laying hens

Eggs of 12 laying hens with 5 mg/kg/day oral administration of 5% enrofloxacin (EFX) or ciprofloxacin (CFX) solution during 5 days contained residues from 0.02 to 1.98 μg/g (EFX) or 0.14 to 0.28 μg/g (CFX). At identical dosage regime High Performance Liquid Chromatograhy (HPLC) residues of EFX were 6-fold greater than CFX ones. Maximun concentrations were detected at the second day after the administration withdrawal. The limits of detection were 0.019 μg/g for EFX and 0.156 μg/g for CFX. The recovery was 36–50% for CFX and 49–85% for EFX. The withdrawal treatment periods in hens are six days for EFX and five days for CFX in order to avoid violative levels of egg residues.     

兽用抗菌药耐药判定标准的研究进展

兽用抗菌药因其可以有效地预防和治疗动物疾病而被广泛使用，造成了严重的细菌耐药。目前，兽药抗菌药的耐药判定主要参考美国临床和实验室标准协会(CLSI)和欧盟药敏试验标准委员会(EUCAST)公布的标准，但数据并不完整。我国近些年也开始建立适合自己国情的兽用抗菌药的耐药判定标准，但成果并不多。因此，急需建立和完善兽用抗菌药的耐药判定标准，以便于监测兽用抗菌药耐药性和指导临床准确使用兽用抗菌药。本文主要综述了CLSI和EUCAST两大组织已经公布的部分兽用抗菌药的耐药判定标准，以及近年来国内外兽用抗菌药耐药判定标准的研究进展，以期为兽用抗菌药耐药判定标准的发展提供理论参考。     

Effects of low levels of the antibiotic ciprofloxacin on the polychaete Hediste diversicolor: biochemical and behavioural effects

The release of pharmaceutical chemicals in the biosphere can have unpredictable ecological consequences, and knowledge concerning their putative toxic effects is still scarce. One example of a widely used pharmaceutical that is present in the aquatic environment is ciprofloxacin. Previous indications suggest that this drug may exert several adverse effects on exposed biota, but the characterization of a full ecotoxicological response to this drug is far from complete, especially in estuarine ecosystems. This work aimed to characterize the acute and chronic effects of ciprofloxacin in the polychaete Hediste diversicolor (Annelida: Polychaeta), exposed to environmentally relevant levels of this drug, close to the real concentrations of this pharmaceutical in surface waters. The adopted toxic endpoints were behavioral parameters, combined with a biomarker-based approach (quantification of the activities of catalase (CAT), glutathione-S-transferase (GSTs), cholinesterases (ChEs), glutathione peroxidase (GPx), and lipid peroxidation levels. Exposure to ciprofloxacin caused effects on behavioural traits, such as an increase in burrowing times and hyperactivity, alongside alterations in biomarkers, including a significant increase in CAT activity following acute exposure. In addition, and after both acute and chronic exposure, lipid peroxidation was reduced, while AChE activities were enhanced. It was possible to ascertain the occurrence of pro-oxidative alterations following exposure to low levels of ciprofloxacin, which were counteracted by the triggering of CAT activity. The meaning of the enhancement of AChE activity is not clear, but it appears to be linked with the observed behavioural changes, and may have been associated with the stimulation of the behavioural traits. These data strongly suggest that the presence of ciprofloxacin in estuarine areas is not without risks, and exposed biota, namely polychaete species, are likely to have their ecological roles affected, thereby compromising the chemical, physical and microbiological stability of sediments, which in turn alters nutrient cycles.     

Enzymatic-microwave assisted extraction and high-performance liquid chromatography-mass spectrometry for the determination of selected veterinary antibiotics in fish and mussel samples

A new method based on enzymatic-microwave assisted extraction prior to high performance liquid chromatography (HPLC) has been developed for the determination of 11 antibiotics (drugs) and the main metabolites of five of them in fish tissue and mussel samples. The analysed compounds were sulfadiazine (SDI), N⁴-acetylsulfadiazine (NDI), sulfamethazine (SMZ), N⁴-acetylsulfamethazine (NMZ), sulfamerazine (SMR), N⁴-acetylsulfamerazine (NMR), sulfamethoxazole (SMX), trimetroprim (TMP), amoxicillin (AMX), amoxicilloic acid (AMA), ampicillin (AMP), ampicilloic acid (APA), chloramphenicol (CLF), thiamphenicol (TIF), oxytetracycline (OXT) and chlortetracycline (CLT).     

Effects of oxytetracycline and amoxicillin on development and biomarkers activities of zebrafish (Danio rerio)

Antibiotics have been widely used in human and veterinary medicine to treat or prevent diseases. Residues of antibiotics have been found in aquatic environments, but their effects on fish have been not properly investigated. This work aimed to assess the sub-lethal effects of oxytetracycline and amoxicillin on zebrafish development and biomarkers. Embryos and adults were exposed during 96 h to amoxicillin and oxytetracycline following OECD guidelines. Tissues of adults and pools of embryos were used for catalase, glutathione-S-transferases and lactate dehydrogenase determinations. Amoxicillin caused premature hatching (48h-EC50 = 132.4 mg/l) whereas oxytetracycline cause delayed hatching of embryos (72h-EC50 = 127.6 mg/l). Moreover, both antibiotics inhibited catalase and induced glutathione-S-transferases in zebrafish adults. However, only oxytetracycline induced lactate dehydrogenase. Short-term effects of antibiotics were observed at high doses (mg/l) indicating that physiological impairment in fish populations is unlike to occur. However, effects of chronic exposures to low doses of ABs must be investigated.     

Effect of various antibiotics on neuromuscular transmission

The effects of streptomycin, neomycin, kanamycin, polymixin and gentamycin on release of acetylcholine from nerve terminal and on muscle twitch were studied using the frog sciatic nerve-gastrocnemius muscle preparation. The first 4 agents were found to be devoid of any inhibitory action on prejunctional acetylcholine release while producing myoneural blockade. Gentamycin reduced acetylcholine output concomitant with myoneural blockade. It is concluded that the first 4 antibiotics act postsynaptically while gentamycin has a presynaptic component of action.     

Effect of triclosan on anuran development and growth in a larval amphibian growth and development assay

A larval amphibian growth and development assay was performed to evaluate the potential effects of environmentally‐relevant concentrations of triclosan (TCS) on amphibian development and growth. Xenopus laevis were exposed to TCS 0.0 (control), 6.3, 12.5 and 25.0 μg l^–1 (estimated maximum tolerable concentration) until 10 weeks post‐metamorphosis. At median metamorphosis time (Nieuwkoop and Faber stage 62), five larvae per replicate were collected for snout–vent length, hind limb length and body weight measurements, and histopathological examination of thyroid glands. Endpoints evaluated at test termination were based on draft guidance (USEPA, 2010 ) and included: survival; snout–vent length; body weight; gender; nuptial pad development (males); and liver, kidney, gonad and gonadal ducts histopathology. Exposure to TCS did not decrease survival, induce general signs of toxicity, affect median metamorphosis time or alter sex ratios. Exposure to TCS 12.5 and 25 μg l^–1 increased growth during the metamorphic stages relative to the control, but did not influence growth during the post‐metamorphic phase. Overall, several statistically significant findings were found in larvae exposed to TCS, such as a decrease in the prevalence of stage 3 Müllerian ducts in the anterior trunk sections of TCS 25.0 μg l^–1 dose group females as compared to controls; most were not considered toxicologically relevant. Copyright © 2017 John Wiley & Sons, Ltd.     

161份抗菌药物说明书的调查与分析

目的：对抗菌药物说明书进行统计分析,发现存在的问题。方法：收集目前使用的抗菌药物说明书161份,阅读整理并进行统计。结果：抗菌药物说明书在老年用药、细菌耐药性、儿童用药、药物过量、孕妇及哺乳期用药、药代动力学等方面不规范。结论：由于抗菌药物被广泛使用,其说明书更应规范,必须加强监督管理。     

剖宫产围手术期预防性应用抗生素的临床分析

目的　探讨择期剖宫产围手术期预防性应用抗生素用药时间、剂量与术后感染的关系。方法　回顾性分析 6 5例择期剖宫产手术病人 ,根据预防性用药方法不同分为 3组 :A组 (围手术期用药组 ) 2 1例 ,选用甲硝唑与头孢噻肟钠 ,于手术前 30min内单次静脉冲击给药 ,术中冲洗宫腔、子宫切口及腹腔留置 ;B组 (手术期及术后用药组 ) 2 4例 ,术中甲硝唑冲洗宫腔、子宫切口及腹腔留置 ,术后头孢噻肟钠用药 3d ;C组 (传统术后用药组 )2 0例 ,术后头孢噻肟钠 +甲硝唑全身用药 5d。结果　术后最高体温、退热时间 3组间差异有统计学意义 (P <0 0 5 ) ;术后病率、腹部伤口感染、子宫内膜炎 3组间差异无统计学意义 (P >0 .0 5 ) ;术后副反应中白细胞计数、胃肠道反应及药物性皮疹 3组间差异无统计学意义 (P >0 .0 5 )。结论　择期剖宫产围手术期预防性使用抗生素安全、有效 ,且剂量小、疗程短 ,优于术后用药。     

浅析我国抗生素滥用的现状及对策研究

通过深入研究分析抗生素滥用原因及产生的危害,探讨控制滥用抗生素的策略。并在此基础上提出了如何减少滥用抗生素的对策,从而维护人类的身心健康,达到切实贯彻《抗菌药物临床应用管理办法》的目的。     

Effects of aflatoxin B1 on tissue residues of enrofloxacin and its metabolite ciprofloxacin in broiler chickens

The impact of subchronic exposure of aflatoxin B1 on the tissue residues of enrofloxacin and its metabolite ciprofloxacin was examined in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750 μg/kg diet) supplemented diets for 6 weeks received enrofloxacin (10 mg/kg/day, p.o.) for 4 days and thereafter, residue levels were determined. Aflatoxin B1 induced alterations in serum marker enzymes. As compared to unexposed broiler chickens, enrofloxacin concentrations in aflatoxin B1-exposed broiler chickens were significantly higher in all tissues (0.62-4.53 μg/g) analyzed except muscle 24h after termination of enrofloxacin administration. Ciprofloxacin was detectable in tissues of only mycotoxin-exposed broiler chickens. Enrofloxacin residues in liver, kidney and skin plus fat persisted for 10 days in mycotoxin-exposed broiler chickens whereas it was detectable only in liver of unexposed broiler chickens. Our results indicate that subchronic aflatoxin B1 exposure markedly influences the residue levels of enrofloxacin and ciprofloxacin in tissues of broiler chickens.     

抗生素对肠道定植抗力的影响研究进展

哺乳动物的胃肠道寄居着复杂的微生物种群,这些微生物种群被称为肠道微生物群,其与宿主的健康和疾病状态息息相关。肠道菌群可以防止外源病原体在胃肠道中定植,这种现象被称为“定植抗力”。对肠道微生态的干扰,譬如抗生素的使用,可能会改变微生物的组成,影响宿主免疫功能,并导致定植抗性的丧失,从而使宿主易于被病原体定植。本文对肠道定植抗力的形成机制以及抗生素对定植抗力影响的研究进展进行综述,旨在为人们合理使用抗生素、研发抗生素替代疗法提供理论参考。     

抗生素不合理应用常见现象分析及对策

目前抗生素在医院的使用中存在着很多不合理的地方,当务之急,要提高临床医生对合理使用抗菌药物的重视程度,促进抗菌药物的合理使用,同时要密切关注临床常用抗生素药的不良反应监测,以减少药品不良反应事件的发生,促进抗生素安全、有效、经济、合理地使用。     

糖肽类抗生素N-甲基无糖万古霉素的分离、纯化和结构鉴定

目的 利用含N-甲基转移酶的粗酶液对无糖万古霉素进行催化,从得到的反应液中分离、纯化N-甲基无糖万古霉素,并进行结构鉴定。方法 利用大孔树脂吸附、中压反相制备色谱等方法进行分离纯化。利用光谱分析,进行结构解析。结果 分离到一个糖肽类化合物N-甲基无糖万古霉素。结论     

我院儿科抗生素的应用分析

目的 了解儿童患者抗生素的使用情况;分析抗生素使用治疗的合理性.方法 对住院及门诊儿童患者的抗生素使用情况进行分析,随机各抽取住院及门诊儿童患者共200例进行回顾性统计分析.结果 在儿童的一般疾病中咳嗽抗生素的使用率达到91.67％,而感冒发热也达到90.77％,所使用的抗生素主要以头孢菌素类为主,联合用药现象不突出.结论 本院儿科使用抗生素较多,抗生素的滥用现象较为严重.医院需加强对医生处方的监管,提高医院整体用药水平.     

我院围手术期预防感染使用抗菌药物的调查分析

目的:了解我院围手术期预防感染抗菌药物使用的情况.方法:抽取我院2003年围手术期预防感染病例1080例,对各项数据进行统计分析.结果:所有手术病例均使用了抗菌药物预防感染,预防用药起点高,用药时机不当,用药持续时间过长,联合用药存在盲目性.结论:我院围手术期预防感染存在许多问题,需加强规范管理,促进抗菌药物的合理使用.