Overexpression of Outer Membrane Protein A Is a Risk Factor for Mortality in <i>Escherichia coli</i> Bloodstream Infections

Abstract

Background. The outer membrane protein A (OmpA) is a virulence factor in Escherichia coli. However, OmpA clinical implication in hospital-acquired infections by E. coli remains unknown. We aimed to determine whether OmpA overexpression is a risk factor associated with the mortality by bloodstream infections by E. coli (BSI-EC). Methods. We analysed demographics, microbiological and clinical data from 190 patients with BSI-EC included in a prospective observational cohort study. OmpA expression by the initial blood cultures isolates was determined using a fluorescence assay based on the introduction of pUA66 plasmid harbouring a transcriptional fusion of green fluorescent protein gene and ompA gene promotor. Bivariate and logistic regression analyses were performed. Results. Dead and survivors patients have homogenous demographics features (age and sex). Dead versus survivor patients presented more comorbidities [higher Charlson score (P<0.001), McCabe score ultimately or rapidly fatal (P<0.001)]. Dead patients had more BSI from gastrointestinal (P=0.013) and primary (P=0.011) focus, severe infections [higher Pitt score (P=0.001) and septic shock frequency (P<0.001)] and more presence of central venous catheter (P<0.05), and nasogastric tube (P<0.001). Isolates from dead patients overexpressed more OmpA than those from survivor patients (36.8x104 vs 28.3x104 a.u., P=0.001). Logistic regression analysis showed OmpA overexpression [OR 1.04 (1.00-1.07); P=0.014], Charlson score [OR 1.33 (1.11-1.60); P=0.002], Pitt score [OR 1.52 (1.14-2.01); P=0.003], the non-urinary tract infection sources of BSI [OR 5.11 (1.86-13.99); P=0.001] as independent risk factors for mortality by BSI-EC. Conclusions. These data indicate that OmpA overexpression is a risk factor for the mortality in patients with BSI-EC. Funding: This work was supported by the Miguel Servet Tipo I Project grant, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades (CP15/00132), and by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spanish Network for Research in Infectious Diseases (RD16/0016/0009), cofinanced by the European Development Regional Fund “A Way to Achieve Europe,” Operative Program Intelligent Growth 2014-2020. Y.S. is supported by the Subprograma Miguel Servet Tipo I, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain [CP15/00132]. A.R.V. is supported by the Subprograma Rio Hortega, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain [CM18/00122]. R.A.M. is supported by the Subprograma Juan Rodes, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain [JR17/00025]. Declaration of Interest: None of the authors have conflicts of interest to declare. Ethical Approval: The study was approved by the Ethics Committee of the University Hospital Virgen del Rocio of Seville (approval no. 0023-N-16). Written informed consent was signed by all patients before inclusion in the study.