Evaluation of molecular epidemiology and risk factors of carbapenem resistant enterobacteriaceae associated bloodstream infections

In recent years, infections associated with carbapenem resistant Enterobacteriaceae (CRE) have been increasingly on the rise, causing a high rate of mortality due to limited treatment options. Early diagnosis and treatment planning, as well as the implementation of effective infection control measures, are important contributions to preventing the spread of these infections and reducing mortality in patients. Knowledge of local incidence rates and the presence of carbapenemase-resistant genes, as well as identifying risk factors in infected patients, can guide the development of hospital-based treatment policies and facilitate the implementation of effective and rapid control measures. The aim of this study was to determine the risk factors for carbapenem resistance and mortality development in patients with Enterobacteriaceae associated bloodstream infections followed in the inpatient services and intensive care units of Pamukkale University Medical Faculty Hospital, as well as to investigate the epidemiology of carbapenemase genes. During a 17 month period from October 2021 to February 2023, 177 patients who were prospectively monitored and diagnosed with Enterobacteriaceae associated bloodstream infections were included in the study. Patients who had non-classified species due to changes in Enterobacteriaceae family classification and those with polymicrobial growth were excluded from the evaluation. Thus, carbapenem resistance and mortality associated risk factors were determined in the remaining 148 patients. Real-time Polymerase Chain Reaction (PCR) molecular testing was used to investigate carbapenemase genes in the obtained CRE isolates. The patients were evaluated in terms of factors that could cause carbapenem resistance and mortality, such as demographic characteristics, the clinics they were followed in, prior antibiotic use before infection, underlying diseases, history of invasive procedures or surgery, and history of intensive care unit admission. Patients with Enterobacteriaceae associated bloodstream infections were statistically compared with patients with carbapenem sensitive Enterobacteriaceae (CSE) associated bloodstream infections. Being followed in the gastroenterology service, presence of chronic kidney disease, use of carbapenem and/or glycopeptide class antibiotics, and history of invasive procedures were found to be statistically significant for CRE associated bloodstream infections (p<0,05). In multivariate logistic regression analysis, the presence of chronic kidney disease (p=0,035), use of carbapenem class antibiotics (p<0,001), and history of invasive procedures (p=0,010) were found to be independent risk factors for the development of CRE associated bloodstream infections. Patients with Enterobacteriaceae associated bloodstream infections were monitored for 14 and 28 days after the collection of culture samples in terms of mortality development. Patients who died after 28 days were evaluated for risk factors that increased mortality. CRE associated bloodstream infections, male gender, admission to the intensive care unit and prolonged hospital stay, use of glycopeptide class antibiotics, presence of urinary catheter, mechanical ventilation support, parenteral nutrition, and ineffective treatment within the first three days after the isolation of the causative agent were identified as significant factors for mortality development (p<0,05). Glasgow Coma Score was significantly lower, while SOFA, Pitt bacteremia, and APACHEII scores were significantly higher in patients who developed mortality (p<0,05). In multivariate logistic regression analysis, the only independent risk factor for mortality development in Enterobacteriaceae associated bloodstream infections was a high SOFA score (p<0,001). The rate of carbapenem resistance was observed as 46% in Enterobacteriaceae isolates obtained from blood cultures. The most common species among carbapenem resistant isolates was K. pneumoniae (71,9%). bla OXA-48 and bla NDM-1 genes were investigated in CRE isolates using Real-time PCR. Alone bla OXA-48 was detected in 35,4% (29) of the strains, alone bla NDM-1 was detected in 15,9% (13), and both genes were detected together in 30,5% (25) of the strains. In conclusion, this study showed that OXA-48 is still the most common carbapenemase enzyme in CRE species in Turkey, but the rate of co-occurrence of NDM-1 and OXA-48 enzymes has increased compared to previous studies. This information can guide the control of carbapenemase genes with changing dissemination frequencies in Turkey and determine treatment strategies according to the gene epidemiology. Knowing the risk factors that may cause carbapenem resistance and mortality development can be beneficial in choose of empirical antibiotic treatment and follow the patients.