Dottorato in MALATTIE INFETTIVE, MICROBIOLOGIA E SANITA' PUBBLICA

Titolo della tesi: The role of intestinal mucosal perturbation and microbial translocation in patients with carbapenem-resistant Klebsiella pneumoniae (CR-Kp) rectal colonization as a risk factor for subsequent CR-Kp bloodstream infections

The role of intestinal mucosal perturbation and microbial translocation in patients with carbapenem-resistant Klebsiella pneumoniae (CR-Kp) rectal colonization as a risk factor for subsequent CR-Kp bloodstream infections Background: Carbapenem Resistant Klebsiella pneumoniae (CR-Kp) rectal colonization is expression of an altered microbiota caused mainly by previous antimicrobial therapies, inducing detrimental effect on the homeostasis of gut flora. Colonization by CR-Kp is considered a prerequisite for subsequent infections, mainly bloodstream infections (BSI). Methods: We conducted a retrospective observational single-center study of adult patients admitted to the Intensive Care Unit after Acute Brain Injury of the Policlinico Umberto 1, Sapienza University of Rome: all patients with rectal colonization by CR-Kp from January 2019 to February 2023 were included. We subsequently assessed markers of microbial translocation (EndoCab IgM and LBP) and intestinal damage (I-FABP) in patients with rectal colonization by Kp- CR (n=22), compared to healthy donors (n=16). Results: Out of 802 patients admitted to the intensive care unit, 133 (16.6%) developed colonization by KPC-Kp. Four patients were excluded as they did not meet inclusion criteria. Among the 129 patients with rectal colonization by KPC-Kp, 47 (36.4%) developed bacteremia (BSI group), while 82 (63.6%) did not (No BSI group). There were no differences in age, gender, comorbidities, SAPS II, and pre-colonization antibiotic treatment between the two groups. However, a significant difference was observed in the Glasgow Coma Scale on admission, which was lower (median 10 No BSI vs. 6 BSI, p=0.0143) in patients who developed BSI, indicating a lower level of consciousness at admission. The Giannella Risk Score at the time of rectal colonization was significantly higher in patients who developed BSI (median 2 No BSI vs. 7 BSI). Furthermore, patients in the BSI group more frequently had another site of colonization by KPC-Kp (74.45%), in addition to rectal swab, compared to No BSI (37.8%), p<0.0001. Analyzing treatments during hospitalization, opioids were more frequently used in the BSI group (95.75%) compared to the No BSI group (80.49%), p<0.0001. The multivariate analysis confirms the use of opioids and the presence of at least one additional site of colonization by KPC-Kp, in addition to the rectal swab, as independently associated risk factors for the development of bloodstream infection (BSI). We subsequently analyzed markers of microbial translocation (MT) and Intestinal damage (ID) in a small number of patients colonized by Kp-CR (n=22) and healthy donors (n=16). The examined markers, (EndoCab IgM, LBP, I-FABP) were found to be altered in colonized patients compared to the healthy donor population, in a statistically significant manner. Discussion and Conclusion: Critical ICU patients after Acute Brain Injury may have peculiar risk factors for developing BSI, this could explain the higher incidence of BSI in our subgroup compared with other studies. We demonstrated that receiving opioids and multisite KPC-Kp colonization were significantly associated with KPC-Kp BSI development. Based on our results, the use of opioids may play a fundamental role in the alteration of the mucosa and contractile activity of the gastrointestinal tract, facilitating microbial translocation; further studies in this area are necessary. The subsequent study of microbial translocation and intestinal damage confirmed a disruption of the barrier in hospitalized colonized patients compared to healthy donors.