Infection caused by (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) producing pathogens increases risk of death on the ICU

Mahableshwar S Albur, Matthew Thomas, Tamas Szackmany

Research output: Contribution to conferenceConference Abstractpeer-review


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.
Original languageEnglish
Publication statusPublished - 4 Oct 2011
Event24th European Society of Intensive Care Medicine (ESICM) Annual meetin - Berlin, Germany
Duration: 1 Oct 20115 Oct 2011


Conference24th European Society of Intensive Care Medicine (ESICM) Annual meetin


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