摘要

用于吸入的妥布霉素溶液（TSI）（诺华制药）被指定为慢性感染铜绿假单胞菌的6岁以上的囊性纤维化（CF）患者的慢性抑制治疗。吸入给药妥布霉素确保了CF患者肺中的高浓度，改善了治疗比率，优于肠外妥布霉素水平。临床和实验室标准研究所（CLSI）断点仅考虑肠胃外水平，并没有考虑到这些高抗菌剂浓度。因此，西班牙meNSURA集团在测试CF铜绿假单胞菌分离株（敏感性：最小抑制浓度（MIC）≤64μg/ ml;耐药：≥128μg/ ml）时已经确定了吸入妥布霉素的具体数值。在此研究中，通过高范围etest试纸条（LIOFILCHEM）测定妥布霉素对120个呼吸性CF铜绿假单胞菌分离株的抗微生物活性。应用MENSURA断点，95％的菌株被归类为易感。使用CLSI断点时，易感率降至92.5％。对于非粘液型铜绿假单胞菌的活性高于粘液分离株（MIC（50）= 0.75和MIC（90）=2μg/ ml对MIC（50）= 1和MIC（90）=4μg/毫升）。从未接受TSI治疗的患者中获得的分离物比接受TSI维持治疗的患者（MIC（50）= 0.75和MIC（90）= 1.5μg/ ml相对于MIC（50）= 1.5和MIC （90）=6μg/ ml）。长期铜绿假单胞菌定植患者（超过5年）的分离物显示出最高的妥布霉素MICs（MIC（50）= 1.00和MIC（90）>1024μg/ ml）。总之，妥布霉素对所研究的CF分离株具有优异的体外活性。一些因素如分离形态类型，TSI预先给药和定殖持续时间影响其活性。每当TSI被考虑用于治疗时，根据CLSI标准，被归类为中等或耐妥布拉霉素的CF铜绿假单胞菌菌株应使用MENSURA解释标准重新分类。

Tobramycin solution for inhalation (TSI) (Novartis pharmaceuticals) is indicated as chronic suppressive treatment for cystic fibrosis (CF) patients aged 6 years and older who are chronically infected by Pseudomonas aeruginosa . Inhaled administration of tobramycin assures high concentrations in the lungs of CF patients, improving the therapeutic ratio over that of parenteral tobramycin levels. Clinical and laboratory Standards institute (CLSI) breakpoints only consider parenteral levels and do not take into account these high antimicrobial concentrations. Therefore, the Spanish meNSURA Group has defined specific values for inhaled tobramycin when testing CF P. aeruginosa isolates (susceptible: minimal inhibitory concentration (MIC) ≤ 64 μg/ml; resistant: ≥ 128 μg/ml). In this study the antimicrobial activity of tobramycin against 120 respiratory CF P. aeruginosa isolates was determined by high-range etest strips (LIOFILCHEM). Applying MENSURA breakpoints, 95% of the strains were categorized as susceptible. With CLSI breakpoints, the susceptibility rate decreased to 92.5%. The activity against non-mucoid P. aeruginosa was higher than that against mucoid isolates (MIC(50)=0.75 and MIC(90)=2 μg/ml vs. MIC(50)=1 and MIC(90)=4 μg/ml). The isolates obtained from patients untreated with TSI were more susceptible to the drug than those from patients receiving maintenance therapy with TSI (MIC(50)=0.75 and MIC(90) =1.5 μg/ml vs. MIC(50)=1.5 and MIC(90)=6 μg/ml). The isolates from patients with long-term P. aeruginosa colonization (over 5 years) revealed the highest tobramycin MICs (MIC(50)=1.00 and MIC(90)>1024 μg/ml). In conclusion, tobramycin has excellent in vitro activity against the studied CF isolates. Some factors such as isolate morphotype, pre-administration of TSI and duration of colonization influence its activity. Whenever TSI is considered for therapy, the CF P. aeruginosa strains categorized as intermediate or resistant to tobramycin according to the CLSI criteria should be recategorized by using the MENSURA interpretive criteria.

https://www.ncbi.nlm.nih.gov/pubmed/21303744