Low-pathogenicity mycoplasma species induce immunoparesis and are highly prevalent amongst patients with ventilator-associated pneumonia

Introduction

Ventilator-associated pneumonia (VAP) remains a significant problem within ICUs. There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms of this immunoparesis remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent amongst patients with VAP than previously recognised, and that these organisms potentially impair immune cell function.

Methods

Two cohorts [1, 2], totalling 159 patients, were recruited from 12 UK ICUs; all patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage. VAP was defined as growth of organisms at >10⁴ CFU/ml on conventional culture. Thirty-six healthy donors underwent lavage for comparison. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. Additionally, healthy donor monocytes and macrophages (MDM) were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed.

Results

Mycoplasmataceae were found in 48% of patients with VAP, compared with 14% of patients without VAP (P < 0.0001). Patients with sterile lavage had a similar prevalence to healthy donor lavage (10 vs. 8%, P = 0.54). The commonest organism identified was M. salivarium. Human blood monocytes and MDM incubated with M. salivarium displayed impaired cytokine responses to lipopolysaccharide and MDM demonstrated impaired phagocytosis.

Conclusion

This study demonstrates a high prevalence of Mycoplasmataceae amongst patients with VAP, with a markedly lower prevalence amongst patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The commonest organism found, M. salivarium, is able to profoundly impair the functions of key immune cells and thus suggests that Mycoplasmataceae may contribute to VAP pathogenesis.