Strateva T, Petrova G, Mitov I
Deaprtment of Medical Microbiology and 1 Pediatric Clinic, Alexandrovska University Hospital, Medical University of Sofia, Bulgaria.
J Chemother. 2010 Dec;22(6):378-83. doi: 10.1179/joc.2010.22.6.378.
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.
吸入用妥布霉素溶液（TSI）（诺华制药）适用于对6岁及以上慢性感染铜绿假单胞菌的囊性纤维化（CF）患者进行长期抑制治疗。吸入妥布霉素可确保CF患者肺部达到高浓度，与静脉注射妥布霉素相比，提高了治疗效果。临床和实验室标准协会（CLSI）的断点仅考虑静脉注射水平，未考虑这些高抗菌浓度。因此，西班牙meNSURA小组在检测CF铜绿假单胞菌分离株时定义了吸入用妥布霉素的特定值（敏感：最低抑菌浓度（MIC）≤64μg/ml；耐药：≥128μg/ml）。在本研究中，通过高范围药敏试验条（LIOFILCHEM）测定了妥布霉素对120株CF呼吸道铜绿假单胞菌分离株的抗菌活性。应用MENSURA断点，95%的菌株被归类为敏感。按照CLSI断点，药敏率降至92.5%。对非黏液型铜绿假单胞菌的活性高于对黏液型分离株的活性（MIC（50）=0.75μg/ml，MIC（90）=2μg/ml，对比MIC（50）=1μg/ml，MIC（90）=4μg/ml）。从未接受TSI治疗的患者分离出的菌株比接受TSI维持治疗的患者分离出的菌株对该药物更敏感（MIC（50）=0.75μg/ml，MIC（90）=1.5μg/ml，对比MIC（50）=1.5μg/ml，MIC（90）=6μg/ml）。长期铜绿假单胞菌定植（超过5年）患者的分离株显示出最高的妥布霉素MIC值（MIC（50）=1.00μg/ml，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，如分离株形态类型、TSI的预先给药和定植持续时间，会影响其活性。每当考虑使用TSI进行治疗时，根据CLSI标准被归类为对妥布霉素中介或耐药的CF铜绿假单胞菌菌株，应使用MENSURA解释标准重新分类。
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