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菌血症性肺炎患者中病原体特异性和宿主特异性特征与疾病转归的关联

Associations of pathogen-specific and host-specific characteristics with disease outcome in patients with bacteremic pneumonia.

作者信息

Sharma-Kuinkel Batu K, Tkaczyk Christine, Bonnell Jessica, Yu Li, Tovchigrechko Andrey, Tabor David E, Park Lawrence P, Ruffin Felicia, Esser Mark T, Sellman Bret R, Fowler Vance G, Ruzin Alexey

机构信息

Division of Infectious Diseases, Department of Medicine, Duke University Durham NC USA.

Microbial Sciences, AstraZeneca Gaithersburg MD USA.

出版信息

Clin Transl Immunology. 2019 Jul 19;8(7):e01070. doi: 10.1002/cti2.1070. eCollection 2019.

Abstract

OBJECTIVE

To understand the relationships of (SA) bacteremic pneumonia (SABP) outcome with patient-specific and SA-specific variables.

METHODS

We analysed SA bloodstream isolates and matching sera in SABP patients by sequencing SA isolates ( = 50) and measuring AT production, haemolytic activity and expression of ClfA and ClfB. Controls were sera from gram-negative bacteremia patients with or without pneumonia and uninfected subjects. Levels of IgGs, IgMs and neutralizing antibodies (NAbs) against SA antigens were quantified and analysed by one-way ANOVA. Associations of patient outcomes with patient variables, antibody levels and isolate characteristics were evaluated by univariate and multivariate logistic regression analyses.

RESULTS

SABP patients had higher levels of IgGs against eight virulence factors and anti-alpha toxin (AT) NAbs than uninfected controls. Levels of IgG against AT and IgMs against ClfA, FnbpA and SdrC were higher in clinically cured SABP patients than in clinical failures. Anti-LukAB NAb levels were elevated in all cohorts. Increased odds of cure correlated with higher haemolytic activity of SA strains, longer time between surgery and bacteremia (> 30 days), longer duration of antibiotic therapy, lower acute physiology and total APACHE II scores, lack of persistent fever for > 72 h and higher levels of antibodies against AT (IgG), ClfA (IgM), FnbpA (IgM) and SdrC (IgM).

DISCUSSION

Limitations included the cross-sectional observational nature of the study, small sample size and inability to measure antibody levels against all SA virulence factors.

CONCLUSION

Our results suggest that SABP patients may benefit from immunotherapy targeting multiple SA antigens.

摘要

目的

了解耐甲氧西林金黄色葡萄球菌(SA)菌血症性肺炎(SABP)的预后与患者特异性及SA特异性变量之间的关系。

方法

我们通过对SA分离株进行测序(n = 50)并测量α毒素(AT)产生、溶血活性以及ClfA和ClfB的表达,分析了SABP患者的SA血流分离株和匹配血清。对照组为患有或未患肺炎的革兰阴性菌血症患者的血清以及未感染的受试者。通过单因素方差分析对针对SA抗原的IgG、IgM和中和抗体(NAb)水平进行定量和分析。通过单因素和多因素逻辑回归分析评估患者预后与患者变量、抗体水平及分离株特征之间的关联。

结果

SABP患者针对八种毒力因子和抗α毒素(AT)NAb的IgG水平高于未感染的对照组。临床治愈的SABP患者中,针对AT的IgG水平以及针对ClfA、FnbpA和SdrC的IgM水平高于临床治疗失败的患者。所有队列中抗LukAB NAb水平均升高。治愈率增加与SA菌株较高的溶血活性、手术与菌血症之间较长的时间间隔(> 30天)、抗生素治疗的较长持续时间、较低的急性生理学和APACHE II总分、无持续发热> 72小时以及针对AT(IgG)、ClfA(IgM)、FnbpA(IgM)和SdrC(IgM)的较高抗体水平相关。

讨论

局限性包括研究的横断面观察性质、小样本量以及无法测量针对所有SA毒力因子的抗体水平。

结论

我们的结果表明,SABP患者可能从针对多种SA抗原的免疫治疗中获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b77/6640002/2dc64cb04025/CTI2-8-e01070-g002.jpg

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