Department of Critical Care, University Hospital of Larissa, Greece; School of Medicine, University of Thessaly, Thessaly, Greece.
Cytogenetics and Molecular Genetics Department, School of Medicine, University of Thessaly, Thessaly, Greece.
J Crit Care. 2018 Oct;47:1-8. doi: 10.1016/j.jcrc.2018.05.012. Epub 2018 May 25.
To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to specific intensive care unit (ICU)-acquired infections and affect outcomes in a Greek ICU.
The incidence of TLR2-Arg753Gln, TLR4-Asp299Gly, TLR4-Thr399Ile and TLR9-T1237C polymorphisms, and their association with ICU-acquired infections and patients' clinical outcomes were prospectively evaluated The examined genetic polymorphisms were assessed by real-time Polymerase-Chain-Reaction (PCR).
During a 15-month period, 224 patients were enrolled and genotyped. The prevalence of genetic polymorphisms for TLR4-Asp299Gly, TLR4-Thr399Ile, mixed TLR4-Asp299Gly/Thr399Ile, TLR9-T1237C and TLR2-Arg753Gln was 14.4%, 14.7%, 11.2%, 24.5% and 2.2%, respectively. TLR4 polymorphisms were associated with increased susceptibility towards specific ICU-acquired infections, i.e. Gram-negative central-nervous-system infections (CNSI), ventilator-associated pneumonia (VAP) and urinary-tract infections (UTI), principally due to multi-drug resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumonia, respectively (all P < 0.05). TLR9-T1237C polymorphism was associated with lower incidence and fewer relapses of CNSIs and UTIs when compared to mixed TLR4-Asp299Gly/Thr399Ile polymorphism group (P ≤ 0.039). ICU-stay was significantly prolonged in TLR4 polymorphisms (P ≤ 0.0416).
Common TLR-signaling polymorphisms might be implicated in the clinical phenotype of ICU-acquired infections in Central Greece. The possible impact of TLR4 polymorphisms on enhanced susceptibility towards Gram-negative MDR-infections in defined critical-disease states warrants further investigation. Trial Registration Clinical Trials.gov identifier: NCT00932243.
检测四种常见 Toll 样受体（TLR）多态性是否可能导致特定的重症监护病房（ICU）获得性感染，并影响希腊 ICU 患者的预后。
前瞻性评估 TLR2-Arg753Gln、TLR4-Asp299Gly、TLR4-Thr399Ile 和 TLR9-T1237C 多态性的发生率，及其与 ICU 获得性感染和患者临床结局的关系。通过实时聚合酶链反应（PCR）检测所研究的遗传多态性。
在 15 个月的时间内，共纳入并对 224 例患者进行了基因分型。TLR4-Asp299Gly、TLR4-Thr399Ile、混合 TLR4-Asp299Gly/Thr399Ile、TLR9-T1237C 和 TLR2-Arg753Gln 遗传多态性的发生率分别为 14.4%、14.7%、11.2%、24.5%和 2.2%。TLR4 多态性与特定 ICU 获得性感染的易感性增加相关，主要是由于多重耐药（MDR）鲍曼不动杆菌、铜绿假单胞菌和肺炎克雷伯菌所致的革兰阴性中枢神经系统感染（CNSI）、呼吸机相关性肺炎（VAP）和尿路感染（UTI）（均 P<0.05）。与混合 TLR4-Asp299Gly/Thr399Ile 多态性组相比，TLR9-T1237C 多态性与 CNSI 和 UTI 的发生率较低和复发较少相关（均 P≤0.039）。TLR4 多态性患者 ICU 住院时间显著延长（P≤0.0416）。
常见 TLR 信号转导多态性可能与希腊中部 ICU 获得性感染的临床表型有关。TLR4 多态性对特定危重病状态下革兰阴性 MDR 感染易感性增加的可能影响需要进一步研究。
NCT00932243。
