In-depth characterization of multidrug-resistant NDM-1 and KPC-3 co-producing Klebsiella pneumoniae bloodstream isolates from Italian hospital patients.

Bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (KP) poses significant challenges, particularly when the infecting isolate carries multiple antimicrobial resistance (AMR) genes/determinants. This study, employing short- and long-read whole-genome sequencing, characterizes six New Delhi metallo-ß-lactamase (NDM) 1 and KP carbapenemase (KPC) 3 co-producing KP isolates, the largest cohort investigated in Europe to date. Five [sequence type (ST) 512] and one (ST11) isolates were recovered from patients who developed BSI from February to August 2022 or February 2023 at two different hospitals in Rome, Italy. Phylogenetic analysis revealed two distinct clusters among ST512 isolates and a separate cluster for the ST11 isolate. Beyond blaNDM-1 and blaKPC-3, various AMR genes, indicative of a multidrug resistance phenotype, including colistin resistance, were found. Each cluster-representative ST512 isolate harbored a blaNDM-1 plasmid (IncC) and a blaKPC-3 plasmid [IncFIB(pQil)/IncFII(K)], while the ST11 isolate harbored a blaNDM-1 plasmid [IncFII(pKPX1)] and a blaKPC-3 plasmid [IncFIB(K)/IncFII(K)]. The blaNDM-1 plasmids carried genes conferring resistance to clinically relevant antimicrobial agents, and the aminoglycoside resistance gene aac(6')-Ib was found on different plasmids. Colistin resistance-associated mgrB/pmrB gene mutations were present in all isolates, and the yersiniabactin-encoding ybt gene was unique to the ST11 isolate. In conclusion, our findings provide insights into the genomic context of blaNDM-1/blaKPC-3 carbapenemase-producing KP isolates.IMPORTANCEThis study underscores the critical role of genomic surveillance as a proactive measure to restrict the spread of carbapenemase-producing KP isolates, especially when key antimicrobial resistance genes, such as blaNDM-1/blaKPC-3, are plasmid borne. In-depth characterization of these isolates may help identify plasmid similarities contributing to their intra-hospital/inter-hospital adaptation and transmission. Despite the lack of data on patient movements, it is possible that carbapenem-resistant isolates were selected to co-produce KP carbapenemase and New Delhi metallo-ß-lactamase via plasmid acquisition. Studies employing long-read whole-genome sequencing should be encouraged to address the emergence of KP clones with converging phenotypes of virulence and resistance to last-resort antimicrobial agents.

First bloodstream infection caused by Prevotella copri in a heart failure elderly patient with Prevotella-dominated gut microbiota: a case report.

BACKGROUND: Bloodstream infection (BSI) is a constant threat for hospitalized patients, and elderly patients are particularly susceptible to BSI caused by anaerobic bacteria. Changes in the gut microbiota composition may lead to pathogen overgrowth and translocation into the bloodstream. Consequently, domination of specific taxa in the intestinal bacterial community seems to be associated with a higher risk of bacteremia in some patient populations. CASE PRESENTATION: Here, we report the case of a 90-year-old heart failure (HF) patient who was admitted to the hospital for an acute state of cardiac decompensation. Twenty days after admission, he was febrile to 38.2 °C whereas his white blood count and C-reactive protein increased to 6190 cells/µL and 31.2 mg/L, respectively. Of the patient's blood culture (BC) bottle pairs collected under the suspicion of infection, the anaerobic bottle yielded an organism that was later identified as Prevotella copri. Concomitantly, the patient's fecal sample was obtained for the intestinal microbiota characterization by sequencing the V3/V4/V6 regions of the bacterial 16S rRNA gene. The analysis revealed highest relative abundances of Bacteroidales (34.1%), Prevotellaceae (19.0%), Prevotella (15.2%), and P. copri (6.1%) taxa, indicating that the patient's gut microbiota was dominated by Prevotella organisms. The patient was successfully treated with metronidazole, and was discharged to a long-term care facility at 35 days of admission. CONCLUSIONS: We provide the first evidence for a clinically significant BSI caused by P. copri and its relationship to a Prevotella-rich gut microbiota in the HF patient setting. When strengthening the pathogenicity of P. copri, the present case suggests that the gut may be a source of BSI caused by the rare anaerobic organism. Future studies are necessary to assess the role of the gut microbiota profiling for precise identification and targeted treatment of patients at high risk of BSI.