兽用抗菌增效剂制剂的研究进展

抗菌增效剂属于人工合成的二氨基嘧啶类药物，此类药物与抗菌药物联合使用时会以特定的机制来增强抗菌药的药物活性。近年来，由于抗生素的广泛使用甚至滥用导致细菌耐药的问题日益显现，通过加入抗菌增效剂而研制出的新制剂可以提高抗菌药在动物体内的利用率、降低药物用量、增强药物疗效、降低兽药残留及减少细菌耐药性。文章分析了近年来甲氧苄啶、二甲氧苄啶和艾地普林与各类抗生素的联合使用制备的制剂产品，发现其对疾病的治疗效果普遍优于单独使用抗生素。同时，配合中药的使用对细菌耐药的问题有显著改善，为后期抗菌增效剂的研究打开新的局面。随着对兽药制剂的研究，其不再局限于简单的剂型，通过运用新技术、新材料研制出的制剂，针对不同的给药部位和给药途径可以对病患进行更精准的治疗，减少药物达到靶部位的时间，增加患病部位的药量，此思路可为后续的研发方向提供支持和参考。文章将对抗菌药-抗菌增效剂联用制剂的研发情况进行综述。     

Advances in Avian Clinical Therapeutics

This article reviews advances in the pharmacokinetics and pharmacodynamics of therapeutic agents used in avian medicine. There has been a significant body of work published within the last 5 years that has helped provide a scientific basis for drug treatment in avian patients. This concise article of different studies on antibacterial, antifungal, analgesic, sedative and anesthetic, hormone (e.g., deslorelin), psychotropic, antiepileptic, and cardiovascular drugs provides evidence of the advancements in this area of companion exotic animal medicine.     

Antimicrobial chemotherapy in the dog

The concept is expounded that, in canine practice, antimicrobial therapy normally should be based on the pharmacology of the drug employed and the therapeutic responses that have been observed to it, as well as a knowledge of the in vitro sensitivities of causal agents. In so doing, information is presented on the concentrations of antimicrobials found to be inhibitory to micro-organisms by in vitro tests and following clinical use. Guide-lines to therapy are related to body systems and organs infected and to Gram-stain reactions of isolates; also presented are dose rates, routes of administration and some general considerations employed when using the antimicrobial drugs for systemic therapy in the dog.     

白色念珠菌分子生物学分型方法研究进展

白色念珠菌是一种致病性酵母真菌,可引起人畜口腔、上呼吸道、阴道黏膜及全身性感染。随着抗真菌药物的长期大量使用,真菌的耐药性越来越严重。临床调查结果表明,白色念珠菌感染在真菌感染病例中跃居第2位。正确鉴定与分类有利于对白色念珠菌感染进行及时诊断、预防和治疗。文章主要对白色念珠菌的分子生物学分型方法进行综述。     

Antifungal agents of use in animal health--chemical,biochemical and pharmacological aspects

A limited number of antifungal agents is licensed for use in animals, however, many of those available for the treatment of mycoses in humans are used by veterinary practitioners. This review includes chemical aspects, spectra of activity, mechanisms of action and resistance, adverse reactions and drug interactions of the antifungals in current use.     

Advances in Exotic Mammal Clinical Therapeutics

It is imperative that the veterinarian treating exotic companion mammals stay abreast of the latest developments relating to medications and drug delivery approaches for safety and efficacy. Sustained-release formulations of commonly used drugs, as well as newer routes for administration of therapeutic agents, allow the veterinarian treating exotic companion mammals to reduce the stress associated with drug administration. Interactions can occur between vehicle and drugs when formulations are compounded; therefore, research studies are warranted regarding potential problems associated with these formulations. However, newer studies have been published that provide the basis for exploring the use of different vehicles, frequency of dosing, and drug delivery techniques for various classes of drugs in exotic mammals. The goals of this review are to not only evaluate new medications or uses for medications in companion exotic mammal patients but also review new methods of drug delivery that might be useful to the veterinarian who treats these animals.     

Pressor Therapy in Critically III Patients

Vasopressors are agents that increase systemic vascular resistance by increasing vasoconstriction. Therapy with intravenous vasopressors may be required in critically ill patients when efforts to optimize cardiac output and blood pressure with intravascular fluid therapy fail. Increasing systemic vascular resistance can promote a favorable perfusion pressure gradient to vital organs in critically ill patients with severe, unresponsive vasodilation. Improperly administered, vasopressors may impede cardiac output and reduce oxygen transport to vital tissue sites. The understanding of systemic and regional effects of vasopressors is currently evolving. Recent literature of the commonly used agents is reviewed. Individual drugs, drug combinations, and potential new therapies are discussed. (Vet. Emerg. & Crit. Care, 10:19–33, 2000)     

Pharmacological approaches towards rationalizing the use of endoparasitic drugs in small animals

Parasitic diseases are an important health concern to small animal veterinarians worldwide, and their zoonotic potential is also of relevance to human medicine. The treatment and control of such conditions relies heavily on pharmaceutical intervention using a range of antiparasitic drugs and/or their biologically active metabolites. Broad spectrum agents have been produced, although narrow and even monospecific drugs are used in some situations. Their efficacy may depend on dosage, the target pathogen(s), the host species and/or the site of infection. Optimal use of antiparasitics requires a detailed consideration of the pharmacokinetic and pharmacodynamic properties of the drugs in specific clinical contexts. This review summarizes the present status of knowledge on the metabolism, and physicochemical and pharmacological properties of the major antiparasitic drugs currently used in small animal veterinary practice. In addition, data relevant to therapeutic dosage, efficacy and clinical indication/contraindication, particularly in relation to combination drug therapy, are included.     

禽光滑念珠菌研究进展

光滑念珠菌逐渐发展成为禽念珠菌属第二大致病菌，该菌通常是口腔、食道、胃肠道的正常菌群，当机体免疫力下降时即表现出对宿主的致病性，菌株一旦进入血液便会扩散到全身，造成系统性念珠菌病。光滑念珠菌主要感染鸡和鸽，临床中以禽食欲减退、消瘦、发育迟缓、羽毛松散和精神沉郁为主要症状，剖检可见嗉囔黏膜表面形成白色假膜或白色圆形隆起溃疡，形似地毯状病变，俗称念珠菌症。光滑念珠菌侵染过程中以酵母形态存在，未见其菌丝形态，入侵时通过形成生物膜来逃避医学灭菌、消毒作用，利用黏附素家族形成的黏附素吸附入侵宿主，依靠水解蛋白酶等相关毒力因子破坏宿主细胞，从而表现出致病性。动物机体以巨噬细胞吞噬及氧化应激反应来抵抗光滑念珠菌的侵染，该菌则通过过氧化氢酶和超氧化物歧化酶两种解毒酶的表达及抗氧化剂谷胱甘肽和硫氧还蛋白的产生来解毒活性氧化物，从而在机体免疫攻击中幸存。为了应对光滑念珠菌感染造成的经济损失，长时间大规模的使用抗真菌药物导致光滑念珠菌耐药性不断增强，对一线抗真菌药物尤其是唑类药表现出高耐药性。研究者逐渐倾向于利用天然物质提取物来解决光滑念珠菌耐药性问题。现从光滑念珠菌病原学、毒力因子及致病性、流行病学、抗菌药物、检测技术等方面进行综述，以期为研制有效抗菌药物防治念珠菌病提供理论依据。     

Antimicrobial use in the surgical patient.

Antimicrobials are often used in the surgical patient in an effort to prevent infection (prophylactic) or to treat established infection (therapeutic). To be effective, prophylactic antimicrobials at appropriate concentrations must be present in tissues at the surgical site at the time of contamination to prevent bacterial growth and subsequent infection. Therapeutic antimicrobials are used to treat established localized or systemic infection. Selection of antimicrobial agents for prophylactic or therapeutic use should be based on knowledge of expected flora, ability of the antimicrobial to reach the target tissue at appropriate concentrations, bacterial resistance patterns, drug pharmacokinetics, and culture and susceptibility testing results (therapeutic use). Failure of antimicrobial therapy to prevent or treat infection in the surgical patient may result from poor antimicrobial selection, inappropriate dosage or frequency, or inappropriate duration of therapy.     

Research Progress on Oxacillin-susceptible Methicillin-resistant Staphylococcus aureus

Staphylococcus aureus (S.aureus) is a gram-positive bacteria which could cause many kinds of infections, such as arthritis, endocarditis cellulitis, septicemia, pyemia and other systemic infections. In recent years, due to the unreasonable use of antibiotics, resistant Staphylococcus aureus increased rapidly.Particularly, the oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA),it is a great challenge for clinical treatment. Understand the epidemiological characteristics and the mechanism of drug resistance of OS-MRSA can help clinicians to choose therapeutic drugs much better. This review summarized the research progress of epidemiology and resistant mechanism of OS-MRSA.     

苯唑西林敏感耐甲氧西林金黄色葡萄球菌研究进展

金黄色葡萄球菌（Staphylococcus aureus,SA）是革兰氏阳性菌,是目前临床感染常见的一种病原菌,能引起局部化脓性感染、关节炎、心内膜炎、蜂窝织炎、败血症、脓毒血症等全身感染。近些年来,由于抗生素不合理的使用,金黄色葡萄球菌的耐药性日益严重,特别是苯唑西林敏感耐甲氧西林金黄色葡萄球菌（oxacillin-susceptible methicillin-resistant Staphylococcus aureus,OS-MRSA）的出现给临床治疗增加了巨大的难度。了解OS-MRSA的流行病学特点和耐药机制可帮助临床医师更好地选择治疗药物,鉴于此,作者针对OS-MRSA的流行病学及耐药机制研究进展进行综述。     

兽用抗菌药物联合用药的PK-PD研究进展

随着养殖业的迅速发展，兽用抗菌药物的应用越来越广泛，但由于抗菌药物的不合理选择与滥用导致细菌对抗菌药物的耐药率在逐渐提高，几乎所有细菌都获得耐药基因。目前，细菌耐药已成为一个全球性问题，并且临床上，疾病病因复杂，常表现为多种病原菌的继发感染和混合感染，单一用药往往难以有效控制疾病，严重危害养殖业发展。抗菌药物的联合用药可以提升药物的治疗效果，缓解或减少不良反应，降低细菌耐药性发生率，对混合感染或不能进行细菌学诊断的病例，联合用药还可扩大抗菌范围。而药物代谢动力学（PK）与药效学（PD）结合模型可以有效综合药物、机体和致病菌之间的相互关系，为临床提供合理用药方案。因此，作者通过介绍联合用药的优势与问题，抗菌药物PK/PD的分类及PK/PD对联合用药给药方案的优化与指导，总结现阶段兽药抗菌药物联合用药的PK-PD研究进展，以期促进兽医临床抗菌药物的合理使用。     

In vitro susceptibility to antimycotics of Microsporum canis isolates from cats.

One hundred thirty-four isolates of Microsporum canis, obtained from cats, were tested for in vitro susceptibility to various antifungal agents. The fungi were classified as susceptible, resistant, and intermediate by measuring the size of the zone of inhibited growth on yeast nitrogen base agar medium. Clotrimazole had the highest activity (99.2%), followed by tioconazole (89.6%), griseofulvin (88.8%), econazole (73.1%), ketoconazole (50.7%), miconazole (15.7%), and isoconazole (12.7%). We found 14.9% of the isolates to be susceptible to all the assayed drugs, whereas the highest resistance frequency (41.8%) was against 2 antimycotics. A simultaneous resistance to all the tested antimycotics was not found. The differences among the antifungal drugs activity were examined, and administration of drugs for which a simultaneous resistance was minimal is suggested.     

Effects of beta-thujaplicin on anti-Malassezia pachydermatis remedy for canine otitis externa

The antifungal activity of beta-thujaplicin was evaluated against 51 Malassezia pachydermatis strains isolated from canine ear canals with or without otitis externa. For comparison, sensitivity tests were performed on M. pachydermatis isolates for nystatin, ketoconazole, and terbinafine HCl, all clinically available antifungal agents. The minimal inhibition concentrations over 50% of the tested isolates (MIC50) were 3.13 microg/ml for beta-thujaplicin and nystatin, 0.016 microg/ml for ketoconazole, and 1.56 microg/ml for terbinafine HCl. The antifungal effect for M. pachydermatis of beta-thujaplicin compared favorably with commercial antifungal agents. None of the 51 M. pachydermatis isolates showed resistance against any of the tested antibiotics investigated in this study. Ten representative isolates of M. pachydermatis were subcultured for 30 generations at concentrations close to the MIC levels of beta-thujaplicin, nystatin, ketoconazole, and terbinafine HCl, and examined to determine whether they had acquired resistance to each drug. As a result, M. pachydermatis was found to achieve resistance more easily for ketoconazole and terbinafine HCl than for beta-thujaplicin or nystatin. The MIC50 of beta-thujaplicin did not change during the course of subculture, and it is thought that the potential development of a resistant strain is low, even with continuous infusion for otitis externa therapy. beta-Thujaplicin is an inexpensive and safe treatment with anti-inflammatory and deodorant effects that can be recommended as an effective remedy for canine otitis externa.     

我国部分地区乳房炎奶样中大肠杆菌的分离鉴定及耐药性分析

为了解我国部分地区奶牛乳房炎奶样中大肠杆菌的耐药情况,以指导牛场合理使用抗生素,提高治疗效果和畜产品质量,从全国六个省市自治区采取158例奶牛乳房炎的奶样,对奶样中的大肠杆菌进行分离纯化与鉴定,并进行药敏试验。结果显示,158份奶样中,共分离出38株大肠杆菌,其中黑龙江18株(分离率为36.0%)、上海3株(分离率6.0%)、北京3株(分离率27.2%)、新疆10株(分离率33.3%)、山东4株(分离率26.7%)、陕西0株(分离率0)。药敏试验显示,磺胺异噁唑耐药率最高,为73.7%;环丙沙星、诺氟沙星、四环素、链霉素药物的敏感率最高,为100%。分离菌株最多耐13种药物,最少耐4种药物,呈现多重耐药性。不同种类的抗生素中,上海和山东对β-内酰胺类药物和氯霉素类药物以及黑龙江、上海和新疆对磺胺类药物的耐药情况比较严重,耐药率高达50%以上。结果表明,各地区分离株对多种抗菌药物产生了不同程度耐药性和多重耐药,临床兽医在治疗时应注意合理用药,提高疗效和畜产品质量,减少耐药性的产生。     

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。     

β-内酰胺类药物对副猪嗜血杆菌流行病学临界值的建立及耐药性的测定

副猪嗜血杆菌病是副猪嗜血杆菌主要针对保育仔猪的一种全身多发性的传染病,对猪场的危害极大。β-内酰胺类抗生素是临床上使用比较多的一类抗生素,具有杀菌活性强、毒性低、适应症广及临床疗效好等优点,常用于治疗副猪嗜血杆菌病,因此有必要了解副猪嗜血杆菌对β-内酰胺类抗生素的耐药情况,从而更科学地指导临床用药和新药开发。本研究参考CLSI-VET和VETCAST中流行病学临界值的建立方法,汇总不同地区来源的菌株对14种β-内酰胺类药物的药敏结果,建立β-内酰胺类药物的流行病学临界值。结果显示,头孢克洛、头孢吡肟、头孢噻肟、头孢喹肟、头孢噻呋、头孢氨苄、阿莫西林-克拉维酸、阿莫西林、克拉维酸、氨苄西林、青霉素、苯唑西林、亚胺培南和美罗培南的流行病学折点值分别为16、0.5、0.125、0.031 25、0.5、32、0.25、1、0.5、1、2、8、0.25、0.062 5 μg·mL^-1,可以得出副猪嗜血杆菌对氨苄西林、阿莫西林以及头孢吡肟的耐药率较高,对亚胺培南和阿莫西林-克拉维酸的敏感性较高。在CLSI （Clinical and Laboratory Standards Institute）和EUCAST （The European Committee on Antimicrobial Susceptibility Testing）缺乏敏感性评判标准的情况下,本研究可以直观地识别非野生型菌株的出现,有利于耐药性监测工作的开展,对副猪嗜血杆菌的治疗和防控具有一定的参考价值。     

New chemotherapy agents in veterinary medicine.

Several anticancer drugs have been added to the therapeutic armamentarium in recent years. Some of these agents are traditional drugs with a long history of use in human oncology. Increased sophistication in clinical trial design in veterinary oncology has allowed the incorporation of agents previously viewed as excessively toxic. Other agents have been developed more recently. This article summarizes the veterinary experience with two older alkylating agents, lomustine and streptozocin, and newer compounds ifosfamide and gemcitabine. The published literature regarding veterinary use of these agents is limited, and the reader is advised to contact a veterinary oncologist for current guidelines when contemplating use of these agents.     

Visual outcome in a group of dogs with ocular blastomycosis treated with systemic antifungals and systemic corticosteroids

OBJECTIVE: To evaluate the success of the use of systemic corticosteroids and antifungal medications in the treatment of dogs with ocular lesions associated with systemic blastomycosis. DESIGN: Retrospective study. ANIMALS STUDIED: Medical records of 25 dogs diagnosed with blastomycosis, via either cytology or histopathology, at the Purdue University Veterinary Teaching Hospital between 1 January 2000 and 1 January 2005, were reviewed. PROCEDURE: Data collected from the medical records included signalment, presence and progression of ocular lesions, antifungal drugs administered, oral and topical corticosteroid administration, length of follow-up, response to treatment, and visual outcome. RESULTS: Of the 25 cases reviewed, 12 dogs (19 eyes) with follow-up information were found to have lesions consistent with ocular blastomycosis. Length of follow-up in the 12 cases ranged from 1 month to 31 months with a mean of 9 months. Antifungal therapy for all cases consisted of oral itraconazole (5 mg/kg every 24 h) initially. In seven cases, the antifungal drug administered was changed from itraconazole to oral fluconazole. Two of these also received intravenous amphotericin B, and two received additional treatment with itraconazole. All 12 dogs also received oral prednisone. The dose of oral prednisone utilized ranged from 0.2 mg/kg/day to 1.4 mg/kg/day with a mean of 0.7 mg/kg/day; the duration of oral prednisone administration ranged from 2 weeks to 8.5 months with a mean of 3 months. Topical prednisolone was a component of the treatment of 16 of the 19 eyes. Duration of topical prednisolone treatment ranged from 1 month to 30 months with a mean of 5 months. Lesions not located in the eyes exhibited a positive response to treatment in 11 (92%) of the 12 dogs. Overall, 14/19 (74%) affected eyes were visual at the time of their final recheck. All eyes with mild or moderate lesions and 5/10 (50%) severely affected eyes were visual at their last recorded recheck examination. CONCLUSIONS: The administration of systemic corticosteroids did not appear to adversely affect the survival rate and might have played a role in preservation of vision in a majority of dogs in this group with ocular blastomycosis.