Resistance and virulence features of hypermucoviscous Klebsiella pneumoniae from bloodstream infections: Results of a nationwide Italian surveillance study

Abstract

Among Enterobacterales, Klebsiella pneumoniae (Kp) is one of the major opportunistic pathogens causing hospital-acquired infections. The most problematic phenomenon linked to Kp is related to the dissemination of multi-drug resistant (MDR) clones producing carbapenem-hydrolyzing enzymes, representing a clinical and public health threat at a global scale. Over the past decades, high-risk MDR clones (e.g., ST512, ST307, ST101 producing blaKPC–type carbepenemases) have become endemic in several countries, including Italy. Concurrently, the spread of highly virulent Kp lineages (e.g., ST23, ST86) able to cause severe, community-acquired, pyogenic infections with metastatic dissemination in immunocompetent subjects has started to be documented. These clones, designated as hypervirulent Kp (hvKp), produce an extensive array of virulence factors and are highly virulent in previously validated animal models. While the prevalence and distribution of MDR Kp has been previously assessed at local and national level knowledge about dissemination of hvKp remains scarce. In this work, we studied the phenotypic and genotypic features of hypermucoviscous (HMV, as possible marker of increased virulence) Kp isolates from bloodstream infections (BSI), obtained in 2016–17 from 43 Italian Laboratories. Antimicrobial susceptibility testing, whole genome sequencing and the use of two animal models (G. mellonella and murine) were employed to characterize collected isolates. Over 1502 BSI recorded in the study period, a total of 19 Kp were selected for further investigation based on their HMV phenotype. Results showed that hvKp isolates (ST5, ST8, ST11, ST25) are circulating in Italy, although with a low prevalence and in absence of a clonal expansion; convergence of virulence (yersiniabactin and/or salmochelin, aerobactin, regulators of mucoid phenotype) and antimicrobial-resistance (extended-spectrum beta-lactamases) features was observed in some cases. Conventional MDR Kp clones (ST307, ST512) may exhibit an HMV phenotype, but with a low virulence potential in the animal models. To the best of our knowledge, this work represents the first systematic survey on HMV and hvKp in Italy, employing a functional characterization of collected isolates. Future surveillance programs are warranted to monitor the threatening convergence of virulence and resistance among MDR Kp and the spread of hvKp.

Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study

“…Our results compare favorably with those reported by large studies, which range from 21% up to 55% [ 25 , 26 , 27 , 28 ]. According to the most recent epidemiological data, we observed a progressive increase in GNB over GPB, with a preponderance of Enterobacteriaceae and non-fermenter bacteria and a peak of MDR pathogens in the 2013–2016 period, as reported also in other Italian centers [ 29 , 30 ]. These findings emphasize the importance to corroborate the awareness of local epidemiology.…”

One-year surveillance for hypervirulent Klebsiella pneumoniae detected carbapenem-resistant superbugs

“…Other sequence types frequently associated with hypervirulence, such as ST5 and ST375, were found in this study. ST5 was previously isolated in Italy in a multicentric study ( 27 ). This strain, as well as hvKp_19 of this study, bears virulence factors such as ICEKp1, aerobactin, salmochelin, and rmpADC hypermucoidy locus.…”

Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients

“…A capsular polysaccharide on the bacterial cell surface plays an important role in the pathogenicity of various bacteria, including Acinetobacter baumannii [ 29 ] and K. pneumoniae [ 30 ]. Although the KL39 capsule type is not generally considered as providing hypervirulence characteristics, at least one recent report described the increased virulence for the isolate having this capsule type and O1/O2v1 O-locus, which was found in all the isolates described above [ 31 ].…”