Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.
Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.
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DOI：
10.1371/journal.pone.0174132
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sokurenko EV
中科院分区：
文献类型：
--
作者：
Tchesnokova V;Avagyan H;Rechkina E;Chan D;Muradova M;Haile HG;Radey M;Weissman S;Riddell K;Scholes D;Johnson JR;Sokurenko EV
尽管已知许多细菌中抗生素耐药性的克隆分布，但经验性（培养前）抗生素选择仍然严重依赖于物种水平的累积耐药谱，导致广谱药物的过度使用和抗生素/病原体过度错配。尿路感染（UTI）占抗生素使用的很大份额，主要由大肠杆菌（一种高度克隆的病原体）引起。在一项对疑似UTI的急诊患者进行的观察性临床队列研究中，我们评估了E。大肠杆菌克隆水平图谱，以改善经验性抗生素选择。建立了一种新的基于PCR的克隆分型方法，用于新鲜尿样中大肠杆菌的快速检测。大肠埃希菌和尿中菌株的克隆型。基于克隆型特异性耐药谱数据库，使用20%、10%和30%的允许耐药阈值推断各种抗生素用于经验性治疗的可接受性。测试的性能特点和可能的影响处方进行了评估。快速试验鉴定出E.在25-35分钟内直接在患者尿液中进行大肠杆菌克隆分型，与培养相比具有高特异性和敏感性。基于克隆型特异性PCR的抗生素选择可将抗生素/病原体错配的相对可能性降低≥ 60%。与观察到的处方模式相比，克隆诊断指导的抗生素选择可以安全地使甲氧苄啶/磺胺甲恶唑的使用增加一倍，并最大限度地减少氟喹诺酮的使用。总之，一种快速克隆分型试验有望改善E.大肠杆菌UTI，包括扭转氟喹诺酮类药物优先使用甲氧苄啶/磺胺甲恶唑。克隆诊断方法结合了流行病学监测、抗菌药物管理和分子诊断，将循证医学直接带到了护理点。
Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients’ urine within 25–35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.