A Combined Phenotypic-Genotypic Predictive Algorithm for In Vitro Detection of Bicarbonate: β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA).
A Combined Phenotypic-Genotypic Predictive Algorithm for In Vitro Detection of Bicarbonate: β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA).
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DOI：
10.3390/antibiotics10091089
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发表时间：
2021-09-09
期刊：
影响因子：
--
通讯作者：
Bayer AS
中科院分区：
文献类型：
--
作者：
Ersoy SC;Rose WE;Patel R;Proctor RA;Chambers HF;Harrison EM;Pak Y;Bayer AS
抗菌药物敏感性试验（AST）通常用于建立预测性抗生素耐药性指标，以指导细菌病原体的治疗。最近，在相对高频率的临床MRSA菌株中鉴定了称为“碳酸氢盐（NaHCO 3）-反应性”的新表型，其中分离株在NaHCO 3存在下对标准β-内酰胺类（苯唑西林[OXA];头孢唑啉[CFZ]）表现出体外“敏感性”，在实验性心内膜炎模型中对这些β-内酰胺类表现出体内敏感性。我们调查了MRSA的靶向表型-基因型筛查是否可以预先排除NaHCO 3敏感性。我们研究了30个充分表征的临床MRSA血流分离株，包括15个在NaHCO 3补充的Mueller-Hinton肉汤（MHB）中对CFZ和OXA敏感的MIC;和15个在该培养基中对两种β-内酰胺类药物均耐药的MIC。采用两层策略，首先通过标准纸片扩散筛选分离株对阿莫西林-克拉维汀[AMC]联合用药的敏感性。然后对分离株进行基因组序列分型：MLST（克隆复合物[CC]）; agr; SCCmec;和mecA启动子和编码区。AMC纸片药敏试验加上mecA和spa基因分型的组合能够预测MRSA菌株或多或少可能在体外对NaHCO 3敏感，具有高度的敏感性和特异性。使用心内膜炎的离体模型，在来自整个队列的6个菌株中进行了该筛选算法的验证。该离体模型概括了上述六种菌株中的五种菌株的NaHCO 3响应性与无响应性的体外预测。
Antimicrobial susceptibility testing (AST) is routinely used to establish predictive antibiotic resistance metrics to guide the treatment of bacterial pathogens. Recently, a novel phenotype termed “bicarbonate (NaHCO3)-responsiveness” was identified in a relatively high frequency of clinical MRSA strains, wherein isolates demonstrate in vitro “susceptibility” to standard β-lactams (oxacillin [OXA]; cefazolin [CFZ]) in the presence of NaHCO3, and in vivo susceptibility to these β-lactams in experimental endocarditis models. We investigated whether a targeted phenotypic-genotypic screening of MRSA could rule in or rule out NaHCO3 susceptibility upfront. We studied 30 well-characterized clinical MRSA bloodstream isolates, including 15 MIC-susceptible to CFZ and OXA in NaHCO3-supplemented Mueller–Hinton Broth (MHB); and 15 MIC-resistant to both β-lactams in this media. Using a two-tiered strategy, isolates were first screened by standard disk diffusion for susceptibility to a combination of amoxicillin-clavulanate [AMC]. Isolates then underwent genomic sequence typing: MLST (clonal complex [CC]); agr; SCCmec; and mecA promoter and coding region. The combination of AMC disk susceptibility testing plus mecA and spa genotyping was able to predict MRSA strains that were more or less likely to be NaHCO3-responsive in vitro, with a high degree of sensitivity and specificity. Validation of this screening algorithm was performed in six strains from the overall cohort using an ex vivo model of endocarditis. This ex vivo model recapitulated the in vitro predictions of NaHCO3-responsiveness vs. nonresponsiveness above in five of the six strains.
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DOI：
10.1016/j.diagmicrobio.2020.115060
发表时间：
2020-07
影响因子：
2.9
作者：
Cunningham SA;Jeraldo PR;Schuetz AN;Heitman AA;Patel R
通讯作者：
Patel R
影响因子：
9.4
作者：
Ferreira, Ines;Beisken, Stephan;Posch, Andreas E.
通讯作者：
Posch, Andreas E.
影响因子：
4.9
作者：
Ersoy, Selvi C.;Chambers, Henry F.;Bayer, Arnold S.
通讯作者：
Bayer, Arnold S.
影响因子：
3
作者：
Abadi, Amin Talebi Bezmin;Rizvanov, Albert A.;Blatt, Nataliya L.
通讯作者：
Blatt, Nataliya L.
影响因子：
6.4
作者：
Goldberg B;Sichtig H;Geyer C;Ledeboer N;Weinstock GM
通讯作者：
Weinstock GM