Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia

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).

Figure 1. Endotoxin concentrations stratified based on febrile status and microbiological findings.

Endotoxin concentrations measured in febrile (n = 103) and afebrile (n = 42) episodes (A). Endotoxin concentrations in febrile neutropaenic episodes with bacteria (n = 37), virus (n = 28) and FUO (n = 38) (B). * p<0.05, *** p<0.0001.

Figure 2. Endotoxin concentrations with (n = 68) and without (n = 77) prophylactic antibiotics use.

Filled circles indicate febrile episodes and open circles indicate afebrile episodes. *p<0.05.

Figure 3. sCD14 concentrations stratified according to microbiological findings.

sCD14 concentrations measured in febrile (n = 103) and afebrile (n = 42) episodes (A). sCD14 concentrations in febrile neutropaenic episodes with bacteria (n = 37), virus (n = 28) and FUO (n = 38) (B). sCD14 concentrations measured in episodes with Gram-positive (n = 21) and Gram-negative (n = 16) bacteria findings (C). * p<0.05, ** p<0.001.