Biofilm Production by Carbapenem-Resistant Klebsiella pneumoniae Significantly Increases the Risk of Death in Oncological Patients

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.

The Impact of Bacterial Biofilms on End-Organ Disease and Mortality in Patients with Hematologic Malignancies Developing a Bloodstream Infection

“…Besides, the lack of a standardized protocol for biofilm characterization further limited a reliable comparative evaluation of the data ( 19 ). In the present study, the use of the BioFilm ring test (cBRT) allowed the early detection and profiling of biofilm-forming bacteria and provided a reliable and standardized tool for diagnosing and monitoring biofilm-associated infections within a routine clinical microbiology platform ( 20 ).…”

“…Samples were collected from a total of 96 adult patients affected by HMs with a BSI. Bacterial identification and antimicrobial susceptibility testing were performed as previously described ( 20 , 30 ). Multidrug-resistant (MDR) bacteria were defined according to the European Centre for Disease Prevention and Control (ECDC) criteria ( https://www.ecdc.europa.eu/en ).…”

“…Biofilm production was assessed by the clinical BioFilm ring test (cBRT) (Biofilm Control, Saint Beauzire, France) as previously described ( 20 ). Each strain was analyzed in duplicate, and experiments were repeated at least two times.…”

First Description of Ceftazidime/Avibactam Resistance in a ST13 KPC-70-Producing Klebsiella pneumoniae Strain from Portugal

“…Our CZA-resistant strain also presented a hypermucoviscosity (HMV) phenotype and genes coding for biofilm production, which are two key factors for colonization and persistence in the host. Notably, infection with biofilm-producing KPC- Kp strains was an independent predictor of mortality [ 39 ]. Worryingly, our strain revealed the presence of the type 3 fimbriae mrkA–mrkJ cluster, including the type 3 fimbriae-related coding genes ( mrkA and mrkD ) and regulation gene ( mrkH ).…”

Comparison of Carbapenem-Resistant Klebsiella pneumoniae Strains Causing Intestinal Colonization and Extraintestinal Infections: Clinical, Virulence, and Molecular Epidemiological Characteristics

“…There were 8 strains that have not been detected in any of bla KPC−2 , bla NDM , bla VIM , bla IMP , or bla OXA−48 , which may be caused by other resistance mechanisms, such as extended-spectrum β-lactamase, efflux pumps and porin mutations ( 31 ). Due to the production of carbapenemase and extended-spectrum β-lactamase ( 32 ), CRKP strains are resistant to general antibacterial drugs such as carbapenem and cephalosporins. At present, only a few drugs, such as colistin, tigecycline, some aminoglycoside drugs, and the recently approved ceftazidime/avibactam, still have good antibacterial activity against CRKP ( 33 – 35 ).…”