Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5 fluoroquinolones toward pathogens of dogs and cats

BACKGROUND: Fluoroquinolones are often used interchangeably in dogs and cats. HYPOTHESIS: Predicted therapeutic efficacy differs among fluoroquinolones. ANIMALS: Bacterial pathogens isolated from dogs and cats. METHODS: Using microtube-dilution procedures, percent resistance and 2 pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10), enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for organisms represented by < or = 15 isolates. RESULTS: Percent resistance for all Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin > or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp. and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose, the proportion of isolates for which a target was reached was: ciprofloxacin, enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%), orbifloxacin (51%), and difloxacin (40%); and at the low dose, enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%), marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%). CONCLUSIONS: E. coli resistance to fluoroquinolones approximated 40%. For susceptible isolates, enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices associated with predicted efficacy, but only at the high dose.     

Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers

Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.     

Comparative effects of fluoroquinolones on subsets of T lymphocytes in normothermic and hyperthermic mice

The subsets of T lymphocytes in thymus, spleen and mesenteric lymph nodes were investigated in normothermic and hyperthermic mice treated with fluoroquinolones administered orally six times at 24 h intervals at doses of 15 or 75 mg/kg (flumequine, norfloxacin and ciprofloxacin) and 5 or 25 mg/kg (enrofloxacin). It has been found that fluoroquinolones can modulate CD3+, CD4+ and CD8+ marker expression on thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Flumequine (15 mg/kg) decreased the percentage of immature CD4+CD8+ thymic cells and increased the percentage of mature CD4+ and CD8+. When the dose of flumequine was increased to 75 mg/kg a reduction in the maturation of thymocytes was observed. Administration of flumequine, norfloxacin and ciprofloxacin, irrespective of doses applied, increased the percentages of CD3+ splenocytes of CD4+ spleen cells. Exposure to enrofloxacin decreased the percentage of T helper-inducer cells. Flumequine and ciprofloxacin augmented the percentage of CD3+ mesenteric lymph node cells and increased the percentage of CD8+ cells. In contrast, norfloxacin and enrofloxacin decreased the percentage of CD3+ mesenteric lymph node cells and the percentage of CD4+ cells. Lipopolysaccharide (LPS) from E. coli (25 micro g/mouse) increased the percentage of single-positive CD4+ thymocytes, but did not affect the percentage of CD3+, CD4+ and CD8+ splenocytes and mesenteric lymph node cells. Flumequine and ciprofloxacin administered to mice pior to LPS potentiated its stimulant effect on the maturation of thymic cells ( increased percentage of mature CD4+ and CD8+ thymocytes). Pre-treatment with norfloxacin or enrofloxacin either reduced or did not modify the stimulant effect of LPS on maturation of thymic cells. Flumequine, norfloxacin, enrofloxacin and ciprofloxacin administered prior to LPS decreased the percentage of CD8+ splenocytes and increased the percentage of CD4+ spleen cells. Norfloxacin and ciprofloxacin at a dose of 75 mg/kg reduced the percentage of CD8+ mesenteric lymph node cells in hyperthermic mice. Pretreatment with norfloxacin at a dose of 15 mg/kg augmented the percentage of mesenteric lymph node cells. It was concluded that the modulating effects of fluoroquinolones depends on the chemial structure of drugs, dose administered as well as immunologic status.     

苯甲酸和精油对肉鸡生长性能、抗氧化状态和肠道微生物群的影响

本研究开展了3个饲养试验,旨在探讨苯甲酸和精油单独或联合使用对肉鸡生长性能、肠道微生物含量及肝脏抗氧化性能的影响。试验1和2均选择1日龄肉鸡450只,分为3组,每组5个重复,每个重复30只。对照组均饲喂相同的基础日粮,试验1处理组肉鸡分别饲喂基础日粮添加1.5和3 g/kg苯甲酸,试验2处理组肉鸡分别饲喂日粮添加2和4 mg/kg精油。试验3选择1日龄肉鸡300只,分为2组,每组5个重复,每个重复30只,对照组饲喂基础日粮,处理组饲喂基础日粮添加1.5 g/kg苯甲酸和4 mg/kg精油。3个试验均开展42 d。结果：试验1,1.5 g/kg苯甲酸组较对照组和3 g/kg苯甲酸组显著提了21和42 d肉鸡的体重及1～21 d、22～42 d、1～42 d日增重（P＜0.05）,同时1.5 g/kg苯甲酸组各阶段肉鸡料重比最低（P＜0.05）。与对照组相比,苯甲酸处理组显著提高了盲肠乳酸菌含量（P＜0.05）,显著降低了盲肠大肠杆菌数量（P＜0.05）。试验2,基础日粮添加4 mg/kg植物精油组42 d肉鸡体重和日增重、盲肠乳酸菌含量（P＜0.05）,料重比和盲肠大肠杆菌数量最低（P＜0.05）。同时,植物精油组较对照组显著提高了肝脏谷胱甘肽过氧化物酶（GSH-Px）和谷胱甘肽-S转移酶（GST）活性（P＜0.05）,显著降低了肝脏丙二醛含量（P＜0.05）。试验3,处理组较对照组显著降低了嗉囊大肠杆菌数量（P＜0.05）。处理组肝脏谷胱甘肽过氧化物酶（GSH-Px）和和谷胱甘肽-S转移酶（GST）活性显著高于对照组（P＜0.05）,但丙二醛含量显著降低（P＜0.05）。结论：日粮添加1.5 g/kg苯甲酸或4 mg/kg精油可以改善肉鸡生长性能,降低肠道有害微生物含量,而苯甲酸与精油无论是单独添加还是联合使用均可以提高肉鸡肝脏的抗氧化状态。 [关键词]苯甲酸|精油|肉鸡|生长性能|抗氧化|微生物     

Susceptibility of canine and feline Escherichia coli and canine Staphylococcus intermedius isolates to fluoroquinolones

OBJECTIVES AND DESIGN: 1) A prospective study to determine in vitro concentrations for a range of fluoroquinolones, gentamicin and amoxycillin-clavulanate required to inhibit growth of recently collected, feline and canine Escherichia coli and canine Staphylococcus intermedius isolates. 2) A comparative retrospective study to compare the minimum inhibitory concentrations (MICs) of ciprofloxacin, enrofloxacin and amoxycillin-clavulanate for archived canine E coli and S intermedius isolates collected ten to twenty years earlier, with those for recently collected isolates. PROCEDURE: Susceptibility was assessed using disk diffusion, agar dilution susceptibility testing and Epsilometer tests (E-tests) for both recently collected and archived isolates. RESULTS: All feline E coli isolates and recently collected canine S intermedius isolates were susceptible to all fluoroquinolones. There was a statistically significant increase in the MIC range of ciprofloxacin and enrofloxacin for recently collected E coli, and in the MIC range of amoxycillin-clavulanate for recently collected S intermedius isolates compared to archived isolates. Twelve of 59 recently collected canine E coli isolates were resistant to both ciprofloxacin and enrofloxacin. Resistant canine E coli isolates were associated with complicating host or infection site factors. CONCLUSION: This is the first report comparing the MICs for all veterinary fluoroquinolones currently available in Australia for a representative sample of canine and feline E coli and canine S intermedius isolates. Importantly, this study identified 12 of 59 canine E coli isolates resistant to fluoroquinolones and identified the development of low level resistance in canine E coli to ciprofloxacin and enrofloxacin and canine S intermedius to amoxycillin-clavulanate.     

The efficacy of bovine lactoferrin in the treatment of cows with experimentally induced Escherichia coli mastitis

The effect of bovine lactoferrin (Lf) was studied in experimental Escherichia coli mastitis, using enrofloxacin as a comparator. Mastitis was induced in six clinically healthy primiparous dairy cows by infusing 1500 colony-forming units of E. coli into a single udder quarter. The challenge was repeated into a contralateral quarter of the same cows 3 weeks later. At the first challenge, three cows were treated with 1.5 g of bovine lactoferrin intramammarily three times (12, 20 and 36 h postchallenge, PC), and the other three cows received 5 mg/kg of enrofloxacin (Baytril) parenterally (12, 36 and 60 h PC). Flunixin meglumine (2.2 mg/kg) was administered to all cows twice at 24-h intervals. During the second challenge, the treatments for the two groups were reversed. Intramammary challenge with E. coli produced clinical mastitis in all cows, but the severity of the disease varied markedly. No statistically significant differences between treatment groups were observed in clinical signs such as rectal temperature, rumen motility and general attitude. Milk somatic cell count, daily milk yield and bacterial counts in cows treated with Lf and those receiving enrofloxacin also did not differ significantly. However, a trend for a more rapid elimination of bacteria was seen in the cows treated with enrofloxacin. Milk NAGase activity also decreased significantly faster in the group treated with enrofloxacin. The concentration of lipopolysaccharide in milk compared with the number of bacteria was significantly lower in Lf than in enrofloxacin-treated cows (20 h PC).     

恩诺沙星对鸡大肠杆菌病及葡萄球菌病的药效研究

就畜禽专用氟喹诺酮类抗菌药恩诺沙星对鸡人工感染大肠杆菌病及葡萄球菌病的药效进行了研究。结果表明，恩诺沙星、氯霉素对大肠杆菌Ｏ７８的ＭＩＣ分别为０．０５、１．６０ｍｇ／Ｌ；恩诺沙星、红霉素对金黄色葡萄球菌Ｃ５６０５株的ＭＩＣ分别为０．２、３．２ｍｇ／Ｌ。人工发病试验中，恩诺沙星内服以５、１０、２０ｍｇ／ｋｇ剂量或肌注以２．５、５、１０ｍｇ／ｋｇ剂量，每天给药２次，连用３ｄ，对鸡大肠杆菌病及葡萄球菌病均有较好的疗效，其中对大肠杆菌病的疗效明显优于氯霉素     

Comparative quantification of the in vitro activity of veterinary fluoroquinolones

The aim of this study was to compare the in vitro antimicrobial activity of the veterinary fluoroquinolones against a panel of recently isolated porcine and bovine bacterial pathogens. The study used enrofloxacin as a benchmark against which other agents were compared, being the most common fluoroquinolone used in treatment of bovine and porcine infections. The activity of ciprofloxacin was also assessed as it is the main metabolite of enrofloxacin in cattle. Enrofloxacin and ciprofloxacin generally showed higher antibacterial activity, in terms of MIC(50) values, for most pathogen species when compared with marbofloxacin, difloxacin, danofloxacin and norfloxacin. Ciprofloxacin showed significantly greater in vitro antibacterial activity than enrofloxacin against M. haemolytica, P. multocida and E. coli, whereas enrofloxacin showed greater activity than ciprofloxacin against S. aureus. Marbofloxacin was significantly more active than enrofloxacin against M. haemolytica, E. coli and B. bronchiseptica but less active against P. multocida, S. aureus, coagulase negative Staphylococci, S. dysgalactiae, S. uberis, A. pleuropneumoniae and S. suis. Danofloxacin was significantly less active than enrofloxacin against P. multocida, E. coli, S. uberis, A. pleuropneumoniae and S. suis. Enrofloxacin and its metabolite ciprofloxacin showed the highest in vitro activities against most bovine pathogens tested and the porcine pathogens also showed a high degree of sensitivity to enrofloxacin. These data facilitate further pharmacokinetic/pharmacodynamic comparison of fluoroquinolones currently used in veterinary medicine.     

In vitro susceptibilities to fluoroquinolones in current and archived Mycoplasma gallisepticum and Mycoplasma synoviae isolates from meat-type turkeys

Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094mug/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values >/=1.0mug/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (相似文献   

Remission of Histiocytic Ulcerative Colitis in Boxer Dogs Correlates with Eradication of Invasive Intramucosal Escherichia coli

Background: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology.
Hypothesis: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission.
Animals: Seven Boxer dogs with HUC.
Methods: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli .
Results: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7±3.06 mg/kg q24 h, for 9.5±3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17–62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed.
Conclusions and Clinical Relevance: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli .     

碱偏离型恩诺沙星注射液的临床应用研究

为了研究碱偏离型恩诺沙星注射液对人工感染大肠杆菌O78雏鸡的治疗作用,本试验以8日龄的雏鸡为试验动物,腹腔注射一定剂量的O78菌悬液,建立雏鸡大肠杆菌人工感染模型,然后给予不同剂量碱偏离型恩诺沙星注射液对其进行治疗试验。结果显示,给予1.75mg/kg碱偏离型恩诺沙星注射液进行预防给药,其增重率显著升高,增重率和有效率分别为102.45%和100%;给予1.75mg/kg碱偏离型恩诺沙星注射液进行治疗给药,雏鸡增重率、治愈率和有效率分别为93.34%、70%和83%,试验证明,碱偏离型恩诺沙星注射液能有效防治人工感染雏鸡大肠杆菌病,为兽医临床应用碱偏离型恩诺沙星注射液治疗雏鸡大肠杆菌病提供了理论依据。     

广东鸡致病性大肠杆菌对氟喹诺酮类药物的敏感性分析

以广东省21个地级市为单位,从鸡场病死鸡分离细菌,选取经生化和动物试验证明的鸡致病性大肠杆菌共115株,采用药敏纸片法测定其对氟喹诺酮类药物的敏感性.结果显示,72.2 %的试验菌对氟喹诺酮类药物产生抗药性;氟喹诺酮类药物之间交叉耐药严重,恩诺沙星与氟罗沙星交叉耐药率高达99%.     

饲粮维生素E水平对43～63日龄黄羽肉鸡肉品质和抗氧化功能的影响

本试验旨在研究饲粮维生素E水平对43 ～ 63日龄黄羽肉鸡肉品质和抗氧化功能的影响.选用1 440只43日龄岭南黄羽肉公鸡,采用单因子随机分组试验设计,共设6个处理,每个处理6个重复,每个重复40只鸡.试验采用玉米淀粉-豆粕型基础饲粮,各处理饲粮营养水平除维生素E水平不同外,其他均相同.空白对照组饲喂未添加维生素E的基础饲粮,其余各处理饲粮中分别添加5、10、20、40、80 mg/kg维生素E.试验期21 d,试鸡地面平养,自由采食颗粒料和自由饮水.结果表明:1)饲粮中维生素E添加水平对试鸡生长性能和胴体品质无显著性影响(P＞0.05).2)胸肌肉色的L*、a*、b *值和肌肉嫩度也未受饲粮维生素E添加水平显著影响(P＞0.05).添加各水平维生素E均显著提高了宰后45 min胸肌pH(P ＜0.05),添加5、10、40、80 mg/kg维生素E均显著提高了宰后24 h胸肌pH(P ＜0.05).添加20、40 mg/kg维生素E显著降低了宰后45 min胸肌滴水损失,添加5、10、40、80 mg/kg维生素E显著降低了宰后48 h胸肌滴水损失(P＜0.05).3)饲粮中添加不同水平维生素E对试鸡血清中丙二醛(MDA)含量和总超氧化物歧化酶(T-SOD)活性无显著性影响(P＞0.05),添加10、20 mg/kg维生素E使试鸡血清中谷胱甘肽过氧化物酶(GSH-Px)活性分别比对照组提高了27.51％、30.57％(P＜0.05).添加各水平维生素E均使试鸡肝脏中GSH-Px活性显著提高(P＜0.05),添加20、40、80 mg/kg维生素E均显著降低了肝脏中MDA含量(P＜0.05),显著提高了肝脏中α-生育酚含量和肌肉中T-SOD活性(P＜0.05).以上试验结果提示,饲粮中添加维生素E可提高43～63日龄黄羽肉鸡机体抗氧化功能,改善肉品质,且添加20 mg/kg效果较好.     

In vitro antibacterial activity of enrofloxacin and ciprofloxacin in combination against Escherichia coli and staphylococcal clinical isolates from dogs

The objective of the study was to determine the in vitro interaction between enrofloxacin and ciprofloxacin against Escherichia coli and staphylococcal isolates from dogs. The microdilution checkerboard assay was used to determine the interaction of the drugs against 50 E. coli and 50 beta-haemolytic staphylococcal clinical isolates. The checkerboard assay revealed that the activity of enrofloxacin and ciprofloxacin was additive against E. coli and staphylococcal clinical isolates. It was concluded that for bacterial species against which ciprofloxacin is more potent than enrofloxacin, the in vivo transformation of enrofloxacin to ciprofloxacin may enhance the efficacy of enrofloxacin, if additivity of the drugs is confirmed in vivo.     

Pharmacokinetics of a single dose of enrofloxacin administered orally to captive Asian elephants (Elephas maximus)

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin after oral administration to captive elephants. ANIMALS: 6 clinically normal adult Asian elephants (Elephas maximus). PROCEDURE: Each elephant received a single dose of enrofloxacin (2.5 mg/kg, PO). Three elephants received their complete diet (pellets and grain) within 2 hours after enrofloxacin administration, whereas the other 3 elephants received only hay within 6 hours after enrofloxacin administration. Serum concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life after oral administration was 18.4 hours for all elephants. Mean +/- SD peak serum concentration of enrofloxacin was 1.31 +/- 0.40 microg/mL at 5.0 +/- 4.2 hours after administration. Mean area under the curve was 20.72 +/- 4.25 (microg x h)/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of enrofloxacin to Asian elephants has a prolonged elimination half-life, compared with the elimination half-life for adult horses. In addition, potentially therapeutic concentrations in elephants were obtained when enrofloxacin was administered orally at a dosage of 2.5 mg/kg. Analysis of these results suggests that enrofloxacin administered with feed in the manner described in this study could be a potentially useful antimicrobial for use in treatment of captive Asian elephants with infections attributable to organisms, such as Bordetella spp, Escherichia coli, Mycoplasma spp, Pasteurella spp, Haemophilus spp, Salmonella spp, and Staphylococcus spp.     

The effects of oral and intramuscular administration and dose escalation of enrofloxacin on the selection of quinolone resistance among Salmonella and coliforms in pigs

The effect of route of administration and dose of enrofloxacin (Baytril) on the development of fluoroquinolone resistance in Salmonella and Escherichia coli in the intestinal tract of pigs was investigated. Healthy pigs at the age of 8-10 weeks were infected with a mixture of susceptible wild-type (MICciprofloxacin = 0.03 microg/ml) and a mutant Salmonella typhimurium with reduced susceptibility to fluoroquinolones (MICciprofloxacin = 0.5 microg/ml) (in the ratio 99:1) and treated with 2.5 mg/kg bwt enrofloxacin by either intramuscular (i.m.) or oral (p.o.) administration at time points either 4 or 24 h after the infection. The treatment via the intramuscular route of administration (24 h after the infection) was carried out with elevated doses of 7.5 and 15 mg/kg bwt as well. Emergence of resistance during a 3-day treatment period and persistence up to 13 days after treatment, was monitored by counting the resistant and total number of coliforms and Salmonella in faeces of the pigs. High frequencies of fluoroquinolone resistance developed rapidly among the coliform flora independent of route of administration, dose or time of initiation of the treatment. Selection for resistance among the artificially introduced Salmonella was reduced by using the intramuscular route and by escalating the dose 3 or 6 times the recommended dose of 2.5 mg/kg bwt, which also resulted in shortening of the period, in which the pigs were shedding Salmonella. The resistance among the coliform flora persisted for at least 2 weeks. The Salmonella infection was cleared in all cases during the 2 weeks independent of frequency of resistance. The study showed that resistance is very easily selected by treatment with enrofloxacin at the recommended dose 2.5 mg/kg bwt, but also that the intensity of selection can be reduced by using intramuscular dosing (instead of oral dosing) and by escalating that i.m. dose. The results obtained with Salmonella also showed that even very small changes in the active drug concentrations might completely change the intensity of selection.     

头孢噻呋钠对1日龄雏鸡实验性感染鸡大肠杆菌病的药效试验

通过预先颈部皮下注射头孢噻呋钠,评价其对1日龄雏鸡试验性诱导大肠杆菌病的预防效果。以微量法测得头孢噻呋钠和恩诺沙星对鸡大肠杆菌的MIC分别为0.1mg/L和1.6mg/L。试验结果表明,0.2、0.1、0.05mg/只的头孢噻呋钠各用药组对人工诱导鸡大肠杆菌病的保护率分别为100%、90%和80%,与0.125mg/只的恩诺沙星对照组(63.33%)及感染对照组(46.67%)相比,头孢噻呋钠各剂量组均能显著降低1日龄雏鸡人工诱发大肠杆菌病的死亡率(P<0.01),具有很好的预防效果;试验结束后细菌学检测结果表明,头孢噻呋钠各剂量组和药物对照组鸡的大肠杆菌检出率分别为13.33%、23.33%、30.0%、46.67%,与感染对照组(90%)相比均显著减少(P<0.01)。     

Fluoroquinolone levels in healthy dog urine following a 20‐mg/kg oral dose of enrofloxacin exceed mutant prevention concentration targets against Escherichia coli isolated from canine urinary tract infections

A 3‐day course of oral enrofloxacin is effective for treating uncomplicated urinary tract infection (UTI) in dogs when administered 20 mg/kg Q24H. However, emergence of fluoroquinolone‐resistant mutants of uropathogens is a concern. Urine concentrations of enrofloxacin and ciprofloxacin were measured in six healthy dogs following dose of enrofloxacin 20 mg/kg. Mutant prevention concentrations of Escherichia coli isolated from canine UTI were also determined against ciprofloxacin. Urine AUC(24)/MPC ratios considering ciprofloxacin concentrations ranged 3819–7767, indicating that selection of resistant E. coli mutants in dogs with uncomplicated UTIs is unlikely in the bladder given that an AUC(24)/MPC = 39 is considered to be protective against mutant selection for ciprofloxacin. However, additional studies are required to evaluate the effects of this enrofloxacin treatment protocol on bacteria that colonize anatomic sites where fluoroquinolones achieve lower concentrations compared to the urinary bladder.     

Excretion pattern of enrofloxacin after oral treatment of chicken broilers

The metabolism and excretion of enrofloxacin were studied when applied as oral solution to chicken broilers for five consecutive days. Sixty 9‐day‐old broilers were isolated within an intensively rearing poultry farm during enrofloxacin therapy (15.5 mg/kg per day). The excreta of the isolated broilers were collected daily, 9 days after therapy termination, for 13 consecutive days, and analyzed for the presence of enrofloxacin and its metabolites [ciprofloxacin, desethylene‐enrofloxacin (DES‐EF) and desethylene‐ciprofloxacin (DES‐CF)]. Enrofloxacin was excreted predominantly in the form of the parent compound between days 1 and 13. Ciprofloxacin was detected in the excreta between days 1 and 6, whereas minor amounts of DES‐EF and DES‐CF were excreted only between days 1–7 and 1–6, respectively. In conclusion, the analysis of the excreta showed that approximately 74% of orally applied enrofloxacin was excreted as the parent compound, approximately 25% as the main metabolite ciprofloxacin, and approximately 1% as the minor metabolites desethylene‐enrofloxacin and desethylene‐ciprofloxacin.     

鸡源大肠杆菌和沙门氏菌的分离鉴定及耐药分析

为探究甘肃省民勤县某饲养场肉仔鸡腹泻的病原及复方中草药制剂和抗生素分别对分离病原的抑菌效果,对7日龄病死肉鸡进行解剖，通过采集死亡肉仔鸡肝脏、脾脏、心脏进行病原菌分离培养、形态观察、16S rDNA分子鉴定，最终鉴定该病死肉仔鸡为大肠杆菌与沙门氏菌混合感染。抑菌结果显示，复方中草药对分离得到的大肠杆菌、鸡白痢沙门氏菌、鸡副伤寒沙门氏菌均有良好的抑菌效果。10种抗生素药敏试验结果显示，此三株菌同时对氨苄西林、环丙沙星、四环素、恩诺沙星四种药物耐药；鸡大肠杆菌对庆大霉素、阿米卡星敏感，鸡白痢沙门氏菌对链霉素、氟苯尼考、头孢噻肟敏感，鸡副伤寒沙门氏菌对头孢曲松、链霉素、头孢噻肟敏感。上述研究结果为肉仔鸡大肠杆菌与沙门氏菌混合感染的分离鉴定以及科学指导用药提供参考。