High-Risk Clone of Klebsiella pneumoniae Co-Harbouring Class A and D Carbapenemases in Italy

Abstract

Background: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is endemic globally, causing severe infections in hospitalized patients. Surveillance programs help monitor and promptly identify the emergence of new clones. We reported the rapid spread of a novel clone of K. pneumoniae co-harbouring class A and D carbapenemases in colonized patients, and the potential risk factors involved in the development of infections. Methods: Rectal swabs were used for microbiological analyses and detection of the most common carbapenemase encoding genes by real-time PCR (i.e., blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP). All strains co-harbouring KPC and OXA-48 genes were evaluated. For each patient, the following variables were collected: age, sex, length and ward of stay, device use, and outcome. Clonality of CR-Kp was assessed by preliminary pulsed field gel electrophoresis (PFGE), followed by multi-locus sequence typing (MLST) analyses. Results: A total of 127 isolates of K. pneumoniae co-harbouring KPC and OXA-48 were collected between September 2019 and December 2020. The median age (IQR) of patients was 70 (61–77). More than 40% of patients were admitted to intensive care unit (ICU). Around 25% of patients developed an invasive infection, the majority of which were respiratory tract infections (17/31; 54.8%). ICU stay and invasive infection increased the risk of mortality (OR: 5.39, 95% CI: 2.42–12.00; OR 6.12, 95% CI: 2.55–14.69, respectively; p-value ≤ 0.001). The antibiotic susceptibility test showed a resistance profile for almost all antibiotics considered. Monoclonal origin was confirmed by PFGE and MLST showing a similar restriction pattern and belonging to ST-512. Conclusions: We report the spread and the marked antibiotic resistance profiles of K. pneumoniae strains co-producing KPC and OXA-48. Further study could clarify the roles of clinical and microbiological variables in the development of invasive infection and increasing risk of mortality, in colonized patients.

A Whole-Genome Sequencing-Based Approach for the Characterization of Klebsiella pneumoniae Co-Producing KPC and OXA-48-like Carbapenemases Circulating in Sardinia, Italy

“…According to international guidelines, a protocol for monitoring antibiotic resistance has been active in our hospital since 2015. As already described in previous reports [ 13 , 41 ], the local epidemiological scenario has shown an increased variability in terms of circulating variants, particularly among carbapenemase-producing Gram-negative bacteria, such as Escherichia coli bla VIM and Enterobacter spp. class A carbapenemase producers.…”

“…As previously reported, the local epidemiological scenario is dominated by the widespread circulation of K. pneumoniae strains that co-produce class A and D carbapenemases, characterized by a pronounced resistance profile against all classes of antibiotics, including the new β-lactam–β-lactamase inhibitors (BL/BLIs) [ 13 ]. Moreover, the production of multiple carbapenemases has led to enhanced virulence and pathogenicity, increasing the risk of progressing from colonization to infection and raising the mortality rate among vulnerable patients [ 13 ]. Here, we aimed to analyze the genetic profile of KPC and OXA-48-like co-producing K. pneumoniae strains, collected in the University Hospital of Sassari (Sardinia, Italy) in a timespan of 1 year, and integrate this information with phenotypic and clinical data.…”

Risk Factors and Outcomes of Community-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection in Elderly Patients

“…The emergence of CRKP is primarily from the different types of carbapenemase production ( K. pneumoniae carbapenemases (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), imipenemase metallo-β-lactamase (IMP), and oxacillinase-48-type carbapenemases (OXA-48)), which further reduce the therapeutic option and increase the mortality risk. [ 3 , 12 , 14 , 15 ]. Furthermore, efflux pump overexpression, decreased outer membrane protein permeability, and beta-lactamase production are all important mechanisms for CRKP strain formation [ 1 , 3 ].…”

“…Moreover, higher morbidity and mortality rates were observed for infections sustained by multidrug resistant strains, due to the reduced therapeutic options [ 11 ]. Elderly patients not only have a higher risk of infectious disease, but are also easily colonized by multi-drug resistant strains, particularly those caused by K. pneumoniae in those with multiple comorbidities [ 12 ]. Extensive studies have focused on the risk factors for hospital-acquired CRKP infection in elderly patients in recent years, revealing that prior antibiotic administration (e.g., cephalosporin, fluoroquinolone, and carbapenems), comorbidities (e.g., diabetes mellitus, malignancy, and cardiovascular disease), and medical interventions (e.g., mechanical ventilation and central venous catheter insertion) were common risk factors [ 11 , 13 ].…”

Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations

“…Results were interpreted according to the clinical breakpoints of the European Union Committee on Antimicrobial Susceptibility Testing, EUCAST v.11.0 [23]. Carbapenemases encoding genes (i.e., blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48 like) were detected by real time-PCR [24].…”