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Infection caused by (e)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (hmb-pp) producing pathogens increases risk of death on the ICU [Abstract]

Szakmany, Tamas, Albur, M., Thomas, M., Eberl, Matthias and Hall, J. E. 2011. Infection caused by (e)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (hmb-pp) producing pathogens increases risk of death on the ICU [Abstract]. Intensive Care Medicine 37 (Supp 2) , S15-S15. 10.1007/s00134-011-2322-1

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Background: Vγ9/Vδ2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. Vγ9/Vδ2 T cells interact with monocytes and become activated by microbial-derived HMB-PP, an essential metabolite produced by a large range of pathogens, which in turn leads to substantial cytokine secretion and the generation of inflammatory response1. Objective: To investigate if infections caused by HMBPP+ve organisms carry higher risk of death in ICU patients. Methods: Retrospective analysis of data collected in the clinical information system of a university and a non-university hospital between 2009-10. Microbiology data was retrieved from the respective databases and paired with patient level data. Microbiologically significant infection was defined as either bacteremia or respiratory secretion cultures with organism concentration > 105 CFU with appropriate clinical manifestations. For statistical analysis Mann-Whitney U test and Chi-square test was used. Results: We identified 3186 patients with 409 clinically significant microbiology cultures. HMBPP+ve pathogens were identified in 227, HMBPP-ve in 182 occasions. Significantly higher ICU mortality was observed with HMBPP+ve infections 60/227 HMBPP+ve vs 33/182 HMBPP –ve, respectively p=0.047 APACHE II LOS Ventilator days Inotropic support (days) HMBPP+ve 18 (9) 7.9 (14) 3 (6) 1 (3) HMBPP-ve 16.5 (8) 6.9 (11) 3 (6) 0.5 (3) Data presented as median and (interquartile range) No significant differences in APACHE II, length of stay, length of advanced respiratory and cardiovascular support was observed. Conclusion: This report is the first to confirm that infection caused by HMBPP+ pathogens carries higher risk of death in ICU patients. This was not attribute to baseline differences as demonstrated by similar APACHE II scores in the HMBPP+ve and –ve group. The exact mechanism behind this phenomenon is unclear, but it has been postulated that a rapid and HMB-PP-dependent crosstalk between the patients Vγ9/Vδ2 T cells and autologous monocytes results in the immediate production of inflammatory mediators. Disproportionate monocyte-γδ T cell crosstalk may result in excessive production of inflammatory mediators, possibly explaining why episodes of HMB-PP+ve sepsis are associated with increased risk of death. Further studies are warranted to investigate this pathway.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: Springer Verlag
ISSN: 0342-4642
Last Modified: 07 Sep 2017 10:46

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