A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease

Daniel G Wootton,Katja Hoschler,Peter J Diggle,Stephen B Gordon,Miriam F Moffatt,Lynne Keogan,Odiri Eneje,Gregory B Gloor,Laura Macfarlane,Esther German,Sarah Wilks,David Litt,Michael J Cox,Mark Woodhead,William O C Cookson,Joanne Court

doi:10.1038/s41598-018-38090-5

Abstract

The demographics and comorbidities of patients with community acquired pneumonia (CAP) vary enormously but stratified treatment is difficult because aetiological studies have failed to comprehensively identify the pathogens. Our aim was to describe the bacterial microbiota of CAP and relate these to clinical characteristics in order to inform future trials of treatment stratified by co-morbidity. CAP patients were prospectively recruited at two UK hospitals. We used 16S rRNA gene sequencing to identify the dominant bacteria in sputum and compositional data analysis to determine associations with patient characteristics. We analysed sputum samples from 77 patients and found a Streptococcus sp. and a Haemophilus sp. were the most relatively abundant pathogens. The Haemophilus sp. was more likely to be dominant in patients with pre-existing lung disease, and its relative abundance was associated with qPCR levels of Haemophilus influenzae. The most abundant Streptococcus sp. was associated with qPCR levels of Streptococcus pneumoniae but dominance could not be predicted from clinical characteristics. These data suggest chronic lung disease influences the microbiota of sputum in patients with CAP. This finding could inform a trial of stratifying empirical CAP antibiotics to target Haemophilus spp. in addition to Streptococcus spp. in those with chronic lung disease.

Highlights

Positive blood cultures from bacteraemic patients who represent an important, but small, proportion of all those with this syndrome
9 samples did not contain mucopurulence and were discarded leaving seventy seven sputum samples to be sequenced. The characteristics of those 77 patients are detailed in Table 1. 16.7% of patients had serological evidence of a recent influenza infection at the time they presented with community acquired pneumonia (CAP). 5/74 (6.8%) of patients grew Streptococcus pneumoniae in their blood culture
The factor which had the greatest effect on the bacterial composition of sputum from adults with CAP was the presence of chronic lung disease

Summary

Introduction

Positive blood cultures from bacteraemic patients who represent an important, but small, proportion of all those with this syndrome. These diagnostic limitations mean most patients receive the same broad spectrum, empirical antibiotic treatment despite wide variations in prior comorbidity, prior medications and age. Very few studies have used generation sequencing to investigate the respiratory microbiota of patients at the time of CAP and they have lacked the clinical detail required to advance antibiotic policy[7,8]. Our aim was to inform trials of stratified, empiric antibiotic therapy by determining how clinical characteristics predict sputum microbiota in this population

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Methods

Results

Conclusion