Effects of sulfamethizole and Amdinocillin against Escherichia coli strains (with various susceptibilities) in an ascending urinary tract infection mouse model
Effects of sulfamethizole and Amdinocillin against Escherichia coli strains (with various susceptibilities) in an ascending urinary tract infection mouse model
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DOI：
10.1128/aac.47.3.1002-1009.2003
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发表时间：
2003-03-01
影响因子：
4.9
通讯作者：
Espersen, F
中科院分区：
文献类型：
--
作者：
Kerrn, MB;Frimodt-Moller, N;Espersen, F
对用于治疗尿路感染（UTIs）的抗生素的耐药性在世界范围内不断增加。体外耐药性对尿路感染临床结局的影响需要进一步研究，因为大多数人类和动物研究仅评估了抗生素对体外敏感细菌的疗效。我们感兴趣的是评价抗生素治疗后体外抗菌效果和体内功效之间的关系。我们通过使用上行性UTI小鼠模型模拟自然上行性UTI，并使用对氨氯西林（美西林）和磺胺甲咪唑具有不同亲和性的大肠杆菌菌株。在标准口服剂量后，用接近人尿路浓度的抗生素剂量处理小鼠3天。对于敏感菌株（MIC，0.5 μ g/ml）和耐药菌株（MIC，128 μ g/ml），分别在用氨地西林治疗后，尿、膀胱和肾脏中的细菌计数显著减少，而对于MIC为16 μ g/ml的菌株，仅肾脏中的细菌计数显著减少（P < 0.05）。用磺胺甲咪唑处理导致敏感菌株（MIC，128 μ g/ml）和抗性菌株（MIC，512 μ g/ml）的所有样品中的细菌计数显著减少。磺胺甲咪唑不能治疗sulII基因阳性菌株感染（MIC>2,048 μ g/ml），因为在尿液、膀胱或肾脏中没有显示出效果。对于氨氯西林，体外敏感性和体内结果之间没有明确的关系，而对于磺胺甲咪唑，我们发现菌株的MIC和尿路效应之间存在关系。
Resistance to antibiotics used for the treatment of urinary tract infections (UTIs) is increasing worldwide. The impact of in vitro resistance on clinical outcome in UTIs requires further study, since most studies of both humans and animals have evaluated only the efficacy of antibiotics toward bacteria susceptible in vitro. We were interested in evaluating the relationship between the in vitro antibacterial effect and the in vivo efficacy after antibiotic treatment. We simulated a natural ascending UTI by use of the ascending UTI mouse model and used Escherichia coli strains with various susceptibilities to amdinocillin (mecillinam) and sulfamethizole. Mice were treated for 3 days with antibiotic doses approximating human urinary tract concentrations after a standard oral dose. For a susceptible strain (MIC, 0.5 mug/ml) and a resistant strain (MIC, 128 mug/ml), respectively, there were significant reductions in bacterial counts in the urine, bladder, and kidneys after treatment with amdinocillin, whereas for a strain for which the MIC was 16 mug/ml, there was a significant reduction in bacterial counts in the kidneys only (P < 0.05). Treatment with sulfamethizole resulted in a significant reduction in bacterial counts in all samples from a susceptible strain (MIC, 128 mu g/ml) and a resistant strain (MIC, 512 mu g/ml). Infection with a sulII gene-positive strain (MIC, >2,048 mug/ml) could not be treated with sulfamethizole, as no effect could be demonstrated in the urine, bladder, or kidneys. For amdinocillin, there was no clear-cut relationship between the in vitro susceptibility and the in vivo outcome, while for sulfamethizole, we found a relationship between the MIC for the strain and the effect in the urinary tract.