Delsol Anne A, Sunderland Julie, Woodward Martin J, Pumbwe Lillian, Piddock Laura J V, Roe John M
Division of Farm Animal Science, Department of Clinical Veterinary Science, Langford BS40 5DU; Bristol Centre for Antimicrobial Research and Evaluation, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, UK.
J Antimicrob Chemother. 2004 May;53(5):872-4. doi: 10.1093/jac/dkh150. Epub 2004 Mar 17.
The effect of a single 5 day enrofloxacin treatment on the native Campylobacter coli population in conventionally weaned 5-week-old pigs was investigated.
Twelve pigs were split into two groups of six: one group was treated with a therapeutic dose (15 mg/pig/day) of enrofloxacin and the other remained untreated to act as the control. Campylobacter coli were isolated from faecal samples and tested for ciprofloxacin resistance by measuring MIC values. Mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene of resistant isolates were identified by sequencing and denaturing HPLC. Levels of enrofloxacin and its primary metabolite ciprofloxacin in the pig faeces were also measured by HPLC.
No quinolone-resistant C. coli (n = 867) were detected in any of the pigs prior to treatment, indicating <0.1% resistance in the group. Resistant C. coli were isolated from pigs for up to 35 days after treatment with a therapeutic dose. These resistant C. coli had MIC values of 128 mg/L and 8-16 mg/L for nalidixic acid and ciprofloxacin, respectively, and the same single point mutation causing a Thr-86 to Ile substitution in the QRDR was identified in each. The concentration of enrofloxacin in the pig faeces was 2-4 micro g/g faeces for the duration of the 5 day therapeutic treatment and was detected up to 10 days post-treatment. Ciprofloxacin was also measured and peaked at 0.6 micro g/g faeces in the treated group.
This study provides evidence that a single course of enrofloxacin treatment contributes directly to the emergence and persistence of fluoroquinolone resistance in C. coli.
研究对常规断奶的5周龄仔猪进行单次为期5天的恩诺沙星治疗对其体内天然空肠弯曲杆菌群体的影响。
12头猪被分成两组，每组6头：一组用治疗剂量（15毫克/猪/天）的恩诺沙星进行治疗，另一组不进行治疗作为对照。从粪便样本中分离出空肠弯曲杆菌，并通过测量MIC值检测其对环丙沙星的耐药性。通过测序和变性高效液相色谱法鉴定耐药菌株gyrA基因喹诺酮耐药决定区（QRDR）中的突变。还通过高效液相色谱法测量猪粪便中恩诺沙星及其主要代谢产物环丙沙星的水平。
治疗前在任何猪中均未检测到喹诺酮耐药的空肠弯曲杆菌（n = 867），表明该组耐药率<0.1%。用治疗剂量治疗后，在猪中可分离出耐药的空肠弯曲杆菌长达35天。这些耐药的空肠弯曲杆菌对萘啶酸和环丙沙星的MIC值分别为128毫克/升和8 - 16毫克/升，并且在每个菌株中均鉴定出在QRDR中导致Thr - 86至Ile取代的相同单点突变。在为期5天的治疗期间，猪粪便中恩诺沙星的浓度为2 - 4微克/克粪便，并且在治疗后长达10天仍可检测到。还测量了环丙沙星，其在治疗组中粪便中的峰值为0.6微克/克。
本研究提供了证据，表明单次恩诺沙星治疗疗程直接导致了空肠弯曲杆菌中氟喹诺酮耐药性的出现和持续存在。
