Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a prominent cause of nosocomial infections associated with high rates of morbidity and mortality, particularly in oncological patients. The hypermucoviscous (HMV) phenotype and biofilm production are key factors for CRKP colonization and persistence in the host. This study aims at exploring the impact of CRKP virulence factors on morbidity and mortality in oncological patients. A total of 86 CRKP were collected between January 2015 and December 2019. Carbapenem resistance-associated genes, antibiotic susceptibility, the HMV phenotype, and biofilm production were evaluated. The median age of the patients was 71 years (range 40–96 years). Clinically infected patients were 53 (61.6%), while CRKP colonized individuals were 33 (38.4%). The most common infectious manifestations were sepsis (43.4%) and pneumonia (18.9%), while rectal surveillance swabs were the most common site of CRKP isolation (81.8%) in colonized patients. The leading mechanism of carbapenem resistance was sustained by the KPC gene (96.5%), followed by OXA-48 (2.3%) and VIM (1.2%). Phenotypic CRKP characterization indicated that 55.8% of the isolates were strong biofilm-producers equally distributed between infected (54.2%) and colonized (45.8%) patients. The HMV phenotype was found in 22.1% of the isolates, which showed a significant (P<0.0001) decrease in biofilm production as compared to non-HMV strains. The overall mortality rate calculated on the group of infected patients was 35.8%. In univariate analysis, pneumoniae significantly correlated with death (OR 5.09; CI 95% 1.08–24.02; P=0.04). The non-HMV phenotype (OR 4.67; CI 95% 1.13–19.24; P=0.03) and strong biofilm-producing strains (OR 5.04; CI95% 1.39–18.25; P=0.01) were also associated with increased CRKP infection-related mortality. Notably, the multivariate analysis showed that infection with strong biofilm-producing CRKP was an independent predictor of mortality (OR 6.30; CI 95% 1.392–18.248; P=0.004). CRKP infection presents a high risk of death among oncological patients, particularly when pneumoniae and sepsis are present. In infected patients, the presence of strong biofilm-producing CRKP significantly increases the risk of death. Thus, the assessment of biofilm production may provide a key element in supporting the clinical management of high-risk oncological patients with CRKP infection.
Highlights
Klebsiella pneumoniae is a major human pathogen with mortality rates up to 50%, in immune-compromised individuals (Kanj and Kanafani, 2011; David et al, 2019)
Susceptibility for colistin and ceftazidime/avibactam was determined by the Sensititre broth microdilution method (Thermo Scientific, New Jersey, USA), and results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints
The presence of blaKPC, blaVIM, blaOXA-48, blaIMP-1, blaNDM types was determined by the Cepheid Xpert® Carba-R assay and the GeneXpert® device (Cepheid, Sunnyvale, USA)
Summary
Klebsiella pneumoniae is a major human pathogen with mortality rates up to 50%, in immune-compromised individuals (Kanj and Kanafani, 2011; David et al, 2019). It causes a broad spectrum of diseases including pneumonia, urinary tract infections, bloodstream infections, skin and soft tissue infections (Melot et al, 2015; Pitout et al, 2015; Paczosa and Mecsas, 2016; David et al, 2019). Novel combinations of b-lactam- b-lactamase inhibitors, such as ceftazidime-avibactam and meropenem-vaborbactam, have been found effective against CRKP producing KPC-type and OXA-48-like enzymes, but not for those strains producing metallo carbapenemases (Bassetti et al, 2018)
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