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直接痰液药敏试验对囊性纤维化痰液的抗菌药物敏感性和协同作用研究。

Antimicrobial susceptibility and synergy studies of cystic fibrosis sputum by direct sputum sensitivity testing.

机构信息

Department of Respiratory Medicine and University of Qld, Mater Adult Hospital Infection, Inflammation and Immunity Program, Mater Medical Research Institute, Lvl 9, Raymond Tce., South Brisbane, QLD, Australia.

出版信息

Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):3211-6. doi: 10.1007/s10096-012-1687-6. Epub 2012 Jul 12.

Abstract

Standard disc diffusion antimicrobial susceptibility testing (C+S) on individual Pseudomonas aeruginosa colonial morphotypes cultured from cystic fibrosis (CF) sputum has questionable clinical relevance. Direct sputum sensitivity testing (DSST) is a whole-sputum susceptibility test that removes bias associated with selecting individual colonial morphotypes. We sought to determine whether, in principle, the results from DSST support the possibility of improved clinical relevance compared with C+S. Individual (DSSTi) and combination (DSST) susceptibility to gentamicin, tobramycin, ceftazidime and meropenem were determined on 130 sputum samples referred from CF subjects with antibiotic-resistant chronic Gram-negative endobronchial infection. DSSTi and concurrent C+S were compared for categorical susceptibility, synergistic combinations were evaluated and the combination DSST efficacy index (DEI) calculated. Meropenem and tobramycin were the most active individual antibiotics by DSSTi on 89 P. aeruginosa-predominant samples, with 62 % of samples sensitive to each. C+S and DSSTi showed poor agreement (κ ranging from 0.02 to 0.6), discordance ranging from 20 % (meropenem) to 49 % (tobramycin), with DSSTi demonstrating both increased susceptibility and increased resistance. The combination that most frequently had the highest DEI was tobramycin + meropenem, occurring in 76 % of samples. DSSTi appears to be reproducible, yields different antimicrobial susceptibility results from C+S without simply identifying the most resistant isolates and DSST identifies the most effective in vitro antibiotic combinations, providing preliminary proof of concept of the potentially improved clinical relevance of whole-sputum testing. Future studies will determine whether these potential theoretical advantages translate into clinical benefits.

摘要

标准的纸片扩散药敏试验(C+S)对从囊性纤维化(CF)痰中培养的单个铜绿假单胞菌菌落形态进行检测,其临床相关性存在疑问。直接痰药敏试验(DSST)是一种全痰药敏试验,可消除选择单个菌落形态所带来的偏倚。我们旨在确定从原则上讲,DSST 的结果是否支持与 C+S 相比提高临床相关性的可能性。对 130 份来自 CF 患者具有抗生素耐药性慢性革兰氏阴性支气管内感染的痰标本进行了单独(DSSTi)和联合(DSST)对庆大霉素、妥布霉素、头孢他啶和美罗培南的药敏试验。比较了 DSSTi 和同时进行的 C+S 的分类药敏性,评估了协同组合,并计算了联合 DSST 功效指数(DEI)。在 89 份以铜绿假单胞菌为主的样本中,DSSTi 对美罗培南和妥布霉素的个体抗生素最有效,每种抗生素的敏感样本比例为 62%。C+S 和 DSSTi 的一致性较差(κ 值范围为 0.02 至 0.6),差异范围为 20%(美罗培南)至 49%(妥布霉素),DSSTi 既显示出更高的敏感性,也显示出更高的耐药性。最频繁出现最高 DEI 的组合是妥布霉素+美罗培南,在 76%的样本中出现。DSSTi 似乎具有可重复性,与 C+S 相比产生了不同的抗菌药敏结果,而不仅仅是确定最耐药的分离株,并且 DSST 确定了最有效的体外抗生素组合,初步证明了全痰检测具有潜在改善的临床相关性。未来的研究将确定这些潜在的理论优势是否转化为临床益处。

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