Carbapenem-resistant Klebsiella Pneumoniae Research Articles

Development of a lytic bacteriophage BPK01 impregnated biopolymer (chitosan) hydrogel for combating high-risk strains of carbapenem resistant Klebsiella pneumoniae (CRKP) pathogens- in vitro and in vivo evaluation.

Development of a lytic bacteriophage BPK01 impregnated biopolymer (chitosan) hydrogel for combating high-risk strains of carbapenem resistant Klebsiella pneumoniae (CRKP) pathogens- in vitro and in vivo evaluation.

Prognosis analysis and infection-related risk factors of multi-drug-resistant bacteria isolated from a general hospital in China, 2019-2023.

Prognosis analysis and infection-related risk factors of multi-drug-resistant bacteria isolated from a general hospital in China, 2019-2023.

Inhaled pH-Responsive polymyxin B-loaded albumin nanoparticles against pneumonia caused by carbapenem resistant Klebsiella pneumoniae.

Inhaled pH-Responsive polymyxin B-loaded albumin nanoparticles against pneumonia caused by carbapenem resistant Klebsiella pneumoniae.

Rapid emergence, transmission, and evolution of KPC and NDM coproducing carbapenem-resistant Klebsiella pneumoniae.

Rapid emergence, transmission, and evolution of KPC and NDM coproducing carbapenem-resistant Klebsiella pneumoniae.

Bloodstream Infections and Colonization in Hematopoietic Stem Cell Transplant Recipients at a South African Center: A Retrospective Analysis.

Bloodstream Infections and Colonization in Hematopoietic Stem Cell Transplant Recipients at a South African Center: A Retrospective Analysis.

Chlorogenic acid inhibits virulence and resistance gene transfer in outer membrane vesicles of carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes. We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms. This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection. These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection.

Identification of a novel phage depolymerase against ST11 K64 carbapenem-resistant Klebsiella pneumoniae and its therapeutic potential.

A novel phage vB_KpnP_IME1309 targeting ST11 K64 carbapenem-resistant Klebsiella pneumoniae (CRKP) was isolated and characterized. The ORF37 encoding depolymerase gene of phage vB_KpnP_IME1309 was successfully expressed and purified. Depolymerase increases the susceptibility of CRKP to serum killing, inhibits CRKP biofilm formation, and degrades mature biofilms. The combination of depolymerase and kanamycin is significantly more effective than either depolymerase or kanamycin alone in the treatment of CRKP biofilm. Depolymerase injection at 5 min and 2 h after CRKP infection of Galleria mellonella larvae increased the survival rate of larvae by up to 73% and 53%, respectively. Depolymerase Dep37 may be used as a method for the development of novel alternative therapeutic strategies against ST11 K64 CRKP.

Carbapenem-resistant Klebsiella pneumoniae infections in Chinese children: in vitro activities of ceftazidime-avibactam and aztreonam-avibactam against carbapenemase-producing strains in a two-center study.

This study assessed epidemiology characteristics, carbapenem-resistance genes, and drug resistance to ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) in children with carbapenem-resistant Klebsiella Pneumoniae (CRKP) infections. A total of 363 non-repetitive CRKP strains were collected from children who underwent two tertiary children's hospital between 1 January 2021 and 30 June 2024 in Chongqing and Kunming in Southwest China. Carbapenem resistance genes and antimicrobial susceptibility were analyzed. Basic clinical characteristics of the patients were obtained from medical records. blaNDM-5, blaNDM-1, and blaKPC-2 were the predominant carbapenemase genes; their detection rates were 35.8%, 30.3%, and 25.3%, respectively. Patients in the KPC-2-producing Klebsiella pneumoniae (KPC-KP) (median age, 90 days) were older than those producing NDM-1 and NDM-5 Klebsiella pneumoniae (NDM-KP) (median age, 37 days) (P < 0.05). The detection rate of NDM-KP in the neonatal unit was higher compared with KPC-KP (62.5% vs. 9.8%, P < 0.05), while the detection rate of NDM-KP in the intensive care unit (ICU) was decreased compared with KPC-KP (9.6% vs. 40.2%, P < 0.05). NDM-KP had lower resistance rates to aminoglycosides and fluoroquinolones than KPC-KP; the resistance rate of aminoglycosides and fluoroquinolones among NDM-KP and KPC-KP in Chongqing was increased compared with Kunming. The sensitivity rates of KPC-KP to CZA and NDM-KP to AZA were 100%, and the MIC50 of the CRKP to CZA and AZA were 2 μg/mL and 0.125μg/mL, respectively. The epidemiological characteristics of Chinese children with CRKP infections, including the resistance genes and the antibiotic resistance of CRKP, exhibited significant variation between the two regions.KPC-KP strains had higher antimicrobial resistance in patients and thus should be given more attention in clinics and infection control.

Increasing polymyxin resistance in clinical carbapenem-resistant Klebsiella pneumoniae strains in China between 2000 and 2023

BackgroundDevelopment of polymyxin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a severe challenge to public health. Here we aimed to perform a retrospective study of prevalence and molecular characteristics of polymyxin-resistant CRKP strains.Methods4455 clinical CRKP strains from 18 provinces in China during 2000 to 2023 were collected. Polymyxin-resistant CRKP strains were subjected to antimicrobial susceptibility testing, whole genome sequencing and bioinformatic analysis. Molecular mechanisms underlying the polymyxin resistance in CRKP were analyzed.ResultsHere we show that polymyxin-resistant CRKP emerge initially in 2014, prevalence of such strains then increase steadily over the years, reaching a rate of 9.86% in 2023. In total, 112 polymyxin-resistant CRKP isolates are identified. Antimicrobial susceptibility tests show that all polymyxin-resistant CRKP are resistant to commonly used antibiotics, yet most isolates remain susceptible only to ceftazidime-avibactam and tigecycline. Predominant polymyxin resistance mechanism in CRKP is mutations in mgrB (59/112), which commonly involves disruption of mgrB by insertion of elements such as ISKpn26 (20/59), IS903B (14/59), and ISKpn14 (9/59). Phylogenetic analysis reveals frequent clonal dissemination of polymyxin-resistant CRKP within the same hospital and even among different hospitals in neighboring provinces. pLVPK-like virulence plasmids are detected in 46 isolates, such strains are therefore categorized as polymyxin and carbapenem-resistant hypervirulent K. pneumoniae which may cause infections with high mortality.ConclusionsOur results highlight frequent clonal transmission of polymyxin-resistant CRKP within hospitals. Continuous surveillance of polymyxin resistance among CRKP should be implemented to prevent further dissemination of such strains in clinical settings in China.

Adaptive attenuation of virulence mediated by Wzc mutation in ST11-KL47 Carbapenem-resistant Klebsiella pneumonia.

The impact of the hypermucoviscosity (HMV) phenotype in ST11-KL47 carbapenem-resistant Klebsiella pneumoniae (CRKp) pathogenicity warrants investigation for public health risk assessment. We analyzed 230 clinical ST11-KL47 CRKp to identify the key factor in mucoviscosity acquisition via comparative genomic analysis. Sedimentation value served as the objective index to quantify HMV. The virulence in vivo was assessed using Galleria mellonella and mouse infection models. We employed genome engineering, capsular polysaccharides (CPS) quantification, and visualization to explore the role of Wzc mutation in CPS biosynthesis and HMV. The biological impact of Wzc-mediated HMV was investigated through competitive growth analysis, biofilm formation, serum resistance, anti-phagocytic ability, and adhesion assays. Transcriptomic analysis and scanning electron microscopy (SEM) were utilized to explore the relationship between polysaccharide composition, physical distribution, and changes in virulence. The Wzc mutations are identified as the key to mucoviscosity acquisition. Unexpectedly, Wzc-mediated HMV CRKp exhibits reduced pathogenicity versus non-mucoviscosity (NMV) strains in different animal models, with competitive disadvantage, decreased biofilm formation, serum resistance, and adhesion, yet higher anti-phagocytic ability in vitro. CPS extraction and visualization of genome-engineered strains verify the Wzc mutations mediate HMV by standardizing CPS chain length and overproducing cell-free extracellular polysaccharides (cell-free EPS). Transcriptomic results, lipopolysaccharides (LPS) quantification, and SEM collectively indicate a downregulation of LPS synthesis and the masking of LPS in HMV strains. These findings demonstrate that the Wzc-induced HMV attenuates ST11-KL47 CRKp virulence by modifying the exopolysaccharide composition and physical distribution.

Assessment of the Diagnostic Accuracy of the Modified Hodge Test and Modified Carbapenem Inactivation Method for Identifying Carbapenem Resistance Mechanisms in Klebsiella pneumoniae: A Whole Genome Sequencing-Based Exploratory Study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major public health concern, particularly in immunocompromised and critically ill patients. Colistin and tigecycline are among the last-resort treatment options, while the primary driver of CRKP emergence is carbapenemase production, especially Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamase (MBL). A thorough understanding of its resistance mechanisms is essential for selecting the most effective antimicrobial therapy. This study aimed to evaluate the diagnostic accuracy of the modified Hodge test (MHT) and modified carbapenem inactivation method (mCIM) in detecting molecular resistance mechanisms in CRKP clinical isolates. This exploratory study consisted of 65 CRKP isolates, which were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany). Antimicrobial susceptibility testing was performed using the BD Phoenix system. The test isolates were subjected to MHTand mCIMand later shipped to the Central Research Laboratory (CRL), Bengaluru, India, where they were subjected to polymerase chain reaction (PCR) and whole-genome sequencing (WGS). PCR detected blaOXA-48-like , blaNDM-1 , bla NDM-5, and blaKPC genes in 79.7%, 10.2%, 64.4%, and 1.7% CRKP isolates, respectively. The PCR results were concordant with WGS. The MHTdemonstrated an overall sensitivity of 60.3%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 4.2% for detecting carbapenemase production. It showed the highest sensitivity and specificity for blaKPC (100%) and blaOXA-48-like (75%) genes, respectively, with the highest PPV for blaOXA-48-like (91.4%) and NPV for blaKPC (100%). However, agreement between MHT and PCR for carbapenemase detection was negligible (Kappa: 0.049, p=0.223). A minimal but statistically significant agreement was noted for blaOXA-48-like detection (Kappa: 0.314, p=0.007), while no significant agreement was observed for blaNDM-1 , blaNDM-5 , or blaKPC genes. The mCIMhad an overall sensitivity of 3.63%, specificity of 100%, PPV of 100%, and NPV of 1.8%. It exhibited the highest sensitivity (4.3%) and specificity (100%) for blaOXA-48-like genes, with the highest PPV for blaOXA-48-like (100%), and NPV for blaKPC (98.1%). No statistically significant agreement was found between mCIM and PCR for carbapenemase detection (Kappa: 0.001, p=0.850). Comprehensive assessment of the diagnostic accuracy of MHT and mCIM using WGS across a broad spectrum of multi-drug-resistant (MDR) organisms should be conducted at multiple centers to produce reliable data that can guide better clinical management of the patients.

Dissemination of blaNDM-harboring plasmids in carbapenem-resistant and hypervirulent Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health threat, and CRKP strains carrying blaNDM plasmids are of particular concern. Here, the antimicrobial resistance and molecular epidemiological characteristics of 59 CRKP strains isolated from patients receiving care at a tertiary hospital in China from 2019 to 2021 were determined through antimicrobial resistance testing and genomic sequence analysis. We analyzed the genetic characteristics and transmissibility of blaNDM-harboring plasmids through S1-digested pulsed field gel electrophoresis, Southern blotting, and conjugation assays. The virulence levels of the strains were evaluated using a Galleria mellonella larvae infection model. All the CRKP strains were multidrug resistant, but none were resistant to colistin or tigecycline. A total of eight sequence types (STs) were detected in these CRKPs, with ST11 (39/59) and ST15 (12/59) being the most common. Among the carbapenemase genes, blaKPC (39/59) and blaNDM (18/59) were the most common, with blaKPC-2 transmitted mainly through ST11 clones and blaNDM-5 transmitted through ST15 clones. The blaNDM-harboring plasmids primarily belong to the incompatibility type IncX3 (14/18). IS26-mediated gene recombination, sequence insertion, and plasmid integration were observed to occur during the dissemination process. The resistance gene profile mediated by blaNDM-harboring plasmids can be transferred through conjugation, which have almost no fitness cost and is extremely stable after passage. Six of these strains presented carbapenem resistance combined with hypervirulence (CR-hvKP), including ST23-KL1, ST218-KL57, ST17-KL112, and ST147-KL64. Additionally, blaNDM-harboring plasmids can disseminate rapidly over large surface areas and persist for a long time in medical institutions, leading to outbreaks of highly resistant clones associated with CR-hvKP.IMPORTANCEThe appearance of plasmids carrying blaNDM and the rise of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have significantly escalated the public health risk associated with Carbapenem-resistant Klebsiella pneumoniae (CRKP). In this study, we described the resistance rates, virulence factors, and molecular epidemiology of 59 CRKP isolated from patients at a tertiary hospital in China from 2019 to 2021. Beyond this, we also assessed the characteristics of blaNDM-harboring plasmids and their dissemination patterns among CRKP, especially some CR-hvKP. Our research contributes to the field of blaNDM dissemination studies, prompting researchers to formulate strict measures to prevent and control the development of blaNDM-harboring plasmids, which is instrumental in the clinical development of targeted treatment plans.

Co-existence of two blaNDM-5 and blaOXA-181 on distinct plasmids in a carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital, Tanzania.

Co-existence of two blaNDM-5 and blaOXA-181 on distinct plasmids in a carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital, Tanzania.

In-vitro susceptibility of cefiderocol and other comparators in carbapenem-resistant Gram-negative bacilli: A study from India.

In-vitro susceptibility of cefiderocol and other comparators in carbapenem-resistant Gram-negative bacilli: A study from India.

Clinical Characteristics, Virulence Profile, and Molecular Epidemiology of Klebsiella pneumoniae Infections in Kidney Transplant Recipients.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may increase the potential for mortality in kidney transplant (KT) recipients. This study aimed to investigate the clinical features, molecular epidemiology, virulence, and antimicrobial resistance of KP strains from KT patients. Strains isolated from KT patients were collected, and antimicrobial susceptibility analysis was verified via the Vitek2 compact instrument and the disc diffusion method. In gene expression analysis, carbapenemase genes (KPC-2, OXA-48, IMP, VIM, NDM), capsular genes (K1, K2, K5, K20, K54, K57), and virulence genes (rmpA, rmpA2, aerobactin, peg344) were identified via polymerase chain reaction (PCR). Molecular epidemiology was analyzed using multilocus sequence typing (MLST) and minimal spanning trees (MST). A total of 43 KP isolates were collected from KT patients in this study, and 24 of them were identified as CRKP (55.81%). KPC-2 genes were detected in all of the CRKP strains (100%), and other carbapenemase genes were not detected. Twenty-two strains (91.67%) of CRKP strains were identified as ST11, while 2 (8.33%) were ST15-typing. Finally, two highly virulent K. pneumoniae strains (both K20-ST268 type) were identified. In addition, the group of CRKP showed a higher deceased kidney donor ratio (p = 0.011), a higher proportion of post-transplant transfers to the ICU (p = 0.037), a higher proportion of late-onset infections (3 months post-transplantation acceptance) (p = 0.007), and high positive rates for the virulence gene rmpA2 (p = 0.01) when comparing the group of carbapenem-sensitive KP. The resistance rate to carbapenem of KP from KT patients exceeded the regional average with predominant ST typing of ST11. Clinical data were analyzed to derive some high-risk factors for CRKP infection. Therefore, we recommend early prophylactic isolation of transplant patients with high-risk factors for CRKP infection to improve the quality of nosocomial control.

Characterization of carbapenem-resistant Klebsiella pneumoniae from blood cultures in Gaza Strip hospitals, Palestine.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult to treat organism owing to limited therapeutic options. So far, little is known about the molecular characteristics of CRKP in Palestine. The aim of this study was to investigate the antimicrobial resistance patterns, multilocus sequence types (ST) and resistance genes among clinical K. pneumoniae isolates from hospitalized patients in Gaza Strip, Palestine. K. pneumoniae from blood cultures (n = 55) were collected at two hospitals in Gaza Strip (2023) and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing was done using VITEK-2 automated systems. Carbapenemases were phenotypically detected. Whole genome sequencing (WGS) of all CRKP isolates was performed to assess determinants for carbapenem resistance and genotypes. Of all K. pneumoniae isolates, 40 % (n = 22/55) were CRKP. Among CRKP, cefiderocol showed the least resistance (46 %, n = 10/22) while ceftazidime/avibactam showed a synergistic effect with aztreonam (36 %, n = 8/22). The majority (86 %, n = 19/22) of CRKP carried metallo-β-lactamases, and only 9 % (n = 2/22) encoded OXA-48 carbapenemase. WGS of CRKP revealed that the predominant genotype is multilocus sequence type ST147 harboring blaNDM-5 and blaCTX-M-15. The proportion of CRKP among all K. pneumoniae from bloodstream infection in Gaza Strip is high (40 %) and mainly associated with the blaNDM-5-positive high-risk clone ST147.

Characterization of OXA232-Producing Carbapenem-Resistant Klebsiella pneumoniae: Genomic Analysis and Virulence Assessment.

Globally, the infection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) producing OXA-48-like carbapenemase is increasing, posing a significant public health threat due to its high antibiotic resistance. Between December 2019 and April 2023, ten CRKP strains carrying the OXA-48-like carbapenemase were isolated from inpatients at the First Affiliated Hospital of Kunming Medical University. Wholegenome sequencing (WGS) revealed that all strains carried the OXA-232 gene, a variant of OXA-48-like, located on the non-conjugative ColKP3 plasmid. Sequence typing identified nine strains as ST231 and one as ST11. The ST231 strains carried common virulence genes, including yersiniabactin (ybtA, fyuA, irp2) and aerobactin (iucABCD, iutA), while the ST11 strain carried high-virulence genes (rmpA, rmpA2, peg-344) as well as KPC-2 and OXA-232 carbapenemase genes on separate plasmids, suggesting that CRKP can harbor multiple plasmids with carbapenemase genes. Sequence typing of 264 global ST231 CRKP isolates (n = 264) showed a distinct clonal relationship between our strains and Indian CRKP isolates, indicating potential cross-border transmission. The virulence potential and immune response of the ST231 strains were assessed using a mouse respiratory infection model. The concentrations of inflammatory factors CCL2/MCP-1, IL-6, and TNF-α in the alveolar lavage fluid and blood of the model mice were detected. Combined with the pathological analysis of lung and liver tissues, it reveals variability in virulence and immune response despite carrying identical resistance and virulence genes. This underscores the urgent need for monitoring and tailored public health strategies to combat the global spread of drug-resistant strains.

World Health Organization priority antimicrobial resistance in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium healthcare-associated bloodstream infections in Brazil (ASCENSION): a prospective, multicentre, observational study.

World Health Organization priority antimicrobial resistance in Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium healthcare-associated bloodstream infections in Brazil (ASCENSION): a prospective, multicentre, observational study.

The hidden threat: Klebsiella pneumoniae may develop co-resistance to colistin and cefiderocol under pressure of colistin.

The hidden threat: Klebsiella pneumoniae may develop co-resistance to colistin and cefiderocol under pressure of colistin.

ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone Harboring Capsular Type KL25 became the primarily prevalent capsular serotypes in a Tertiary Teaching Hospital in China.

ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone Harboring Capsular Type KL25 became the primarily prevalent capsular serotypes in a Tertiary Teaching Hospital in China.