Abstract

In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).

Highlights

  • Neutropenia is a common complication in patients undergoing chemotherapy for malignancies and is one of the most important risk factors for infections

  • Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in fever of unknown origin (FUO) episodes whilst episodes with documented bacterial (104.7 pg/mL [IQR = 87.1 pg/mL–112.3 pg/mL]) and viral (97.3 pg/mL [IQR = 85.45 pg/mL–109.4 pg/mL]) findings were similar (Figure. 1b)

  • No correlation was observed between viral findings and endotoxin concentrations

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Summary

Introduction

Neutropenia is a common complication in patients undergoing chemotherapy for malignancies and is one of the most important risk factors for infections. [2] Today, bacteraemia is identified in 23%–33% [3,4,5,6,7] of all patients, and studies of the viral contribution to the aetiological panorama are still limited but estimated to be 30% [8]. This leaves, approximately a third of febrile episodes unexplained despite extensive microbiological investigations and these are termed fever of unknown origin (FUO). Elevated endotoxins had been reported in studies with immunocompromised cohorts, for example, HIV-1 [11] and patients with haematological malignancies and is used as a measure of microbial translocation. [12,13,14,15]

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