Oropharyngeal colonization by Gram-Negative bacilli is higher in hospitalized patients than in healthy subjects: a French case - control study

Ventilator-associated pneumonia (VAP) is the most common severe nosocomial infection in Intensive Care Units (ICU), causing significant inpatient morbi-mortality and driving antibiotic consumption. Oropharyngeal colonization with pathogenic organisms is considered a major factor for the development of VAP and Gram-negative bacilli (GNB) are the most frequently implicated pathogens. The prevalence of GNB oropharyngeal colonization (GNB-OPC) in ICU and non-ICU patients, as well as oropharyngeal carriage of multidrug resistant (MDR) bacteria in the community, remain unclear. We conducted a prospective multicenter study in which 100 healthy subjects and 389 hospitalized patients, admitted in ICU or in three different surgery wards (orthopaedic, digestive or thoracic), were included for screening for GNB-OPC. Samples from hospitalized patients were collected at admission, day 5 and day 10 or at discharge, while healthy subjects were sampled only on the day of inclusion. GNB isolates were identified, tested for antibiotic susceptibility and Enterobacterales strains resistant to third-generation cephalosporins were sequenced. Demographic data and clinical characteristics were collected and risk factors analysed. GNB-OPC was significantly higher in hospitalized patients on admission than in healthy subjects (OR = 9.0, 95%CI [3.2–25.1]; P < 0.0001). The risk of GNB-OPC varied significantly by ward type, with orthopaedic surgery as reference and showing the lowest risk (Risk Difference ranging between 21.4 and 25.2, P = 0.0004). Other factors significantly associated with GNB-OPC at admission were male gender, tobacco and chronic alcohol consumption as well as several comorbidities (solid-organ cancers and cardiovascular disease). GNB-OPC acquisition during hospitalization was low for all patients. Among hospitalized patients, 3.5% of oropharyngeal swabs were positive with third-generation cephalosporin-resistant Enterobacterales , in particular with high-risk transmissible clones, such as ST405 K. pneumoniae and O25:H4 ST131 fimH 30 E. coli resistant isolates. The GNB-OPC prevalence is very low in healthy subjects. Significantly lower in patients admitted in orthopaedic surgery ward, than in those admitted in the other wards, GNB-OPC are correlated with intrinsic patients’ characteristics. Asymptomatic oropharyngeal carriage of high-risk transmissible clones is observed in patients admitted in ICU, and should be considered to prevent an inadequate treatment and delay in appropriate management of HAP. ClinicalTrails.gov NCT02839980 date: 21 July 2016 ‘prospective registered’.