Wiuff C, Lykkesfeldt J, Svendsen O, Aarestrup F M
Danish Veterinary Institute, Bülowsvej 27, DK-1790 Copenhagen V, Denmark.
Res Vet Sci. 2003 Dec;75(3):185-93. doi: 10.1016/s0034-5288(03)00112-7.
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.
研究了恩诺沙星（拜有利）的给药途径和剂量对猪肠道中沙门氏菌和大肠杆菌氟喹诺酮耐药性产生的影响。选用8 - 10周龄的健康猪，用对氟喹诺酮敏感的野生型（环丙沙星MIC = 0.03μg/ml）和对氟喹诺酮敏感性降低的鼠伤寒沙门氏菌突变体（环丙沙星MIC = 0.5μg/ml）按99:1的比例混合感染，在感染后4小时或24小时通过肌肉注射（i.m.）或口服（p.o.）给予2.5mg/kg体重的恩诺沙星进行治疗。通过肌肉注射途径给药（感染后24小时）时，也采用7.5mg/kg体重和15mg/kg体重的高剂量。在为期3天的治疗期间监测耐药性的出现情况，并在治疗后长达13天监测耐药性的持续情况，方法是对猪粪便中的大肠菌群和沙门氏菌的耐药菌数和总数进行计数。无论给药途径、剂量或治疗开始时间如何，大肠菌群中氟喹诺酮耐药性的高频率都迅速出现。通过肌肉注射途径以及将剂量提高至推荐剂量2.5mg/kg体重的3倍或6倍，可减少人工引入的沙门氏菌中的耐药性选择，这也导致猪排出沙门氏菌的时间缩短。大肠菌群中的耐药性至少持续2周。在2周内，所有病例中的沙门氏菌感染均被清除，与耐药频率无关。该研究表明，按推荐剂量2.5mg/kg体重用恩诺沙星治疗很容易选择出耐药性，但通过肌肉注射给药（而非口服给药）并提高肌肉注射剂量，可降低选择强度。沙门氏菌的研究结果还表明，活性药物浓度即使有非常小的变化也可能完全改变选择强度。
