Characterisation of Candida within the Mycobiome/Microbiome of the Lower Respiratory Tract of ICU Patients

Abstract

Whether the presence of Candida spp. in lower respiratory tract (LRT) secretions is a marker of underlying disease, intensive care unit (ICU) treatment and antibiotic therapy or contributes to poor clinical outcome is unclear. We investigated healthy controls, patients with proposed risk factors for Candida growth in LRT (antibiotic therapy, ICU treatment with and without antibiotic therapy), ICU patients with pneumonia and antibiotic therapy and candidemic patients (for comparison of truly invasive and colonizing Candida spp.). Fungal patterns were determined by conventional culture based microbiology combined with molecular approaches (next generation sequencing, multilocus sequence typing) for description of fungal and concommitant bacterial microbiota in LRT, and host and fungal biomarkes were investigated. Admission to and treatment on ICUs shifted LRT fungal microbiota to Candida spp. dominated fungal profiles but antibiotic therapy did not. Compared to controls, Candida was part of fungal microbiota in LRT of ICU patients without pneumonia with and without antibiotic therapy (63% and 50% of total fungal genera) and of ICU patients with pneumonia with antibiotic therapy (73%) (p<0.05). No case of invasive candidiasis originating from Candida in the LRT was detected. There was no common bacterial microbiota profile associated or dissociated with Candida spp. in LRT. Colonizing and invasive Candida strains (from candidemic patients) did not match to certain clades withdrawing the presence of a particular pathogenic and invasive clade. The presence of Candida spp. in the LRT rather reflected rapidly occurring LRT dysbiosis driven by ICU related factors than was associated with invasive candidiasis.

The lung mycobiome in the next-generation sequencing era

“…Finally, in the only published study on pneumonia, which is the largest lung mycobiome study to date, Krause et al compared BAL from 87 healthy controls, 18 patients with extrapulmonary infection on antibiotics, 8 intensive care unit patients without antibiotics, 23 intensive care unit patients with extrapulmonay infection on antibiotics, 34 intensive care unit patients with pneumonia on antibiotics, and 32 patients with candidemia. 18 They focused on Candida and found that intensive care unit admission, but not antibiotic therapy, shifted the lung mycobiome to be dominated by Candida. Even this recent study still used culture-based fungal identification as the gold-standard for fungal identification, as this is standard practice in a clinical setting.…”

Mycobiome in the Lower Respiratory Tract – A Clinical Perspective

“…However, the association was mainly derived from two patients with preceding antibiotic therapy and antifungal therapy and the contribution of fungal or bacterial microbiota to lung function could not be distinguished. Despite variable fungal composition in LRT, Candida overall dominated mycobiota in most of the studies including CF patients, lung transplant patients, HIV infected patients and ICU patients (Bousbia et al, 2012; Charlson et al, 2012; Bittinger et al, 2014; Willger et al, 2014; Cui et al, 2015; Kramer et al, 2015a; Krause et al, 2016). In remaining studies with dominating fungi other than Candida methodologies were too weak to draw profound conclusions.…”

“…In two previous studies reagents (e.g., saline, lab water, lab surfaces) have been analyzed to assess its influence on microbiota results from BAL (Bittinger et al, 2014; Krause et al, 2016); however, in other studies this was not done (Erb-Downward et al, 2011; van Woerden et al, 2011, 2013). Nevertheless, none of the studies investigating reagents showed that Candida abundance reached >50% as has been found in BAL samples from ICU patients (Krause et al, 2016).…”

“…Smoking behavior of study patients was not evaluated. All study subjects were without antimycotic treatment ≥8 weeks prior to sampling (Krause et al, 2016). LRT in all patients and healthy study subjects were sampled through endotracheal tubes avoiding contact to the oral cavity.…”

“…Sampling techniques (endobronchial secretion versus BAL) showed similar results and saline did not influence mycobiota results. The results showed that Candida was part of the fungal microbiota of various intubated and mechanically ventilated ICU patients with and without antibiotic therapy and with and without pneumonia (59–73% Candida signatures within 5–8 fungal genera; Krause et al, 2016). Candida sequences were not present in mycobiota of non-ICU patients with antibiotic therapy and healthy controls.…”