Hypervirulent Klebsiella pneumoniae (hvKP) typically causes severe invasive infections affecting multiple sites in healthy individuals. In the past, hvKP was characterized by a hypermucoviscosity phenotype, susceptibility to antimicrobial agents, and its tendency to cause invasive infections in healthy individuals within the community. However, there has been an alarming increase in reports of multidrug-resistant hvKP, particularly carbapenem-resistant strains, causing nosocomial infections in critically ill or immunocompromised patients. This presents a significant challenge for clinical treatment. Early identification of hvKP is crucial for timely infection control. Notably, identifying hvKP has become confusing due to its prevalence in nosocomial settings and the limited predictive specificity of the hypermucoviscosity phenotype. Novel virulence predictors for hvKP have been discovered through animal models or machine learning algorithms, while standardization of identification criteria is still necessary. Timely source control and antibiotic therapy have been widely employed for the treatment of hvKP infections. Additionally, phage therapy is a promising alternative approach due to escalating antibiotic resistance. In summary, this narrative review highlights the latest research progress in the development, virulence factors, identification, epidemiology of hvKP, and treatment options available for hvKP infection.

A 42-year-old man was admitted to the emergency room complaining of fever and headache. His cerebrospinal fluid showed a cloudy appearance, and his white blood cell count was elevated at 2460/mm3, with a predominance of neutrophils (81%), and abnormal protein and glucose levels (510.7 mg/dL and 5 mg/dL, respectively). A lobulated lesion with rim enhancement, suggestive of abscess, was detected through magnetic resonance imaging. Klebsiella pneumoniae was detected in nasopharyngeal swab and blood cultures. The capsular serotype of K. pneumoniae was K2 and the sequence type determined by multilocus sequence typing was 23. The hypervirulent phenotype was associated with multiple virulent genes, including rmpA, rmpA2, entB, ybtS, kfu, iucA, iutA, iroB mrkD, allS, peg-344, peg-589, and peg-1631. After six weeks of receiving appropriate antibiotics and exhibiting clinical resolution of the brain abscesses, the patient was discharged. We present the first reported case of a healthy community-dwelling adult with solitary brain abscesses, and no other invasive abscesses, related to hypervirulent K. pneumoniae.

Hypervirulent K. pneumoniae infection has been raising worldwide and is one of the major causes of community-acquired pyogenic liver abscess. We described a case report of pyogenic liver abscess caused by an atypical hypervirulent (non-hypermucoviscous) K. pneumoniae K1 ST23 in a diabetic Asian patient who resided in Mexico. The susceptibility to antimicrobials, pathogenicity, molecular and genomic analysis were determined. A man from Guangdong (China) with a recent diagnosis of diabetes mellitus was admitted to the hospital, and he denied traveling in the last 3 months. A computed tomography revealed a right lobe liver abscess. On the third day after admission a Klebsiella pneumoniae isolate (14652) was obtained. The isolate corresponded to a susceptible K. pneumoniae with capsular type K1 and ST23 (CG23) and exhibited a non-hypermucoviscous phenotype. The isolate 14652 was genetically related to the globally distributed lineage ST23-KL1. This study describes the first case in Mexico of K. pneumoniae capsular type K1 and ST23 with an atypical hypervirulent phenotype.

The liver receives blood from both the hepatic artery and portal vein. Hepatic infarction is rare in clinical practice as both the hepatic artery and portal vein can supply blood to the liver. Here, we reported a case of a 75-year-old man who underwent radical laparoscopic surgery for rectal cancer and subsequently developed hepatic infarction. The patient experienced severe infection, as well as circulatory and respiratory failure on the third day after surgery. The patient presented with high fever, chest tightness, shortness of breath, decreased blood oxygen saturation and blood pressure. The leukocyte count decreased from 8.10 × 10^9/L to 1.75 × 10^9/L. Procalcitonin (PCT) levels increased from 1.02 ng/mL to 67.14 ng/mL, and eventually reaching levels over 200 ng/mL. Enhanced abdominal computed tomography (CT) confirmed the presence of hepatic infarction, but no thrombosis was observed in the hepatic artery or portal vein. Metagenomic next-generation sequencing (mNGS) identified hypervirulent Klebsiella pneumoniae (hvKp) in the patient\'s blood and ascites, one day earlier than the detection results using traditional culture methods. The patient was diagnosed with hepatic infarction combined with septic shock caused by hvKp. This case emphasizes that in the high-risk group of thrombosis, infection can trigger exacerbated hepatic infarction events, particularly in cases after surgical procedures. For severely ill patients with infectious diseases who are admitted to the ICU with worsening symptoms, it is important to collect appropriate samples and send them for pathogen detection using mNGS in a timely manner. This may aid in early intervention and improve clinical outcomes.

Invasive infection caused by hypervirulent Klebsiella pneumoniae (HvKP) has been reported worldwide. Most of the patients are community population, related to diabetes mellitus (DM), chronic liver disease and other basic diseases, which prone to systemic migratory infection. In this study, we collected 377 patients with community acquired Klebsiella pneumoniae liver abscess in our hospital from January 2013 to December 2018, 65.8% of whom were male, and 49.6% had DM. Patients with DM are prone to eye and central nervous system (CNS) infection, which need continuous local abscess drainage during treatment. Among them, patients with poor blood glucose control have a higher rate of blood stream infections (BSI). 219 strains of HvKP were obtained, with K1/K2 Serotype accounted for 81.7%. The incidence of BSI in K2 patients was higher than that in K1 patients. The PCR results indicate that the carrying rate of virulence genes (rmpA、areo、kfu、allS、iroN、magA、uge、wcaG) in K1/K2 type strains is significantly higher than that in non K1/K2 type strains. ST23 and ST65 are the most common multilocus sequence typing (MLST), which belong to K1 and K2 Serotype respectively. All of HvKP strains showed high sensitivity to commonly used clinical antibiotics other than ampicillin, with 54.3% of the strains exhibiting high viscosity characteristics. Meanwhile, 35 classic Klebsiella pneumoniae (cKP) strains were collected, and their serum typing is mainly non K1/K2. The carrying rate of virulence genes and viscosity degree in HvKP are significantly higher than those in cKP. Primary liver abscess caused by HvKP is prone to multiple tissue and organ infections, but it shows higher sensitivity to most commonly used antibiotics in clinical practice except for ampicillin. After effective treatment, the overall prognosis of patients is better. This study analyzes the pathogenic characteristics of HvKP and elaborates on the clinical characteristics of patients, which can provide reference for clinical and scientific research work.
高毒力肺炎克雷伯菌(hypervirulent Klebsiella pneumoniae，HvKP)造成侵袭性感染已在全球范围内被广泛报道，其感染者主要集中在患有糖尿病(diabetes mellitus，DM)、慢性肝病等基础疾病的社区人群，且容易发生全身迁徙性感染。本研究收集了本院2013年1月~2018年12月社区获得性肺炎克雷伯菌肝脓肿患者377名，男性占65.8%，其中49.6%有DM。DM患者易发生眼部及中枢神经系统(central nervous system，CNS)感染，治疗过程中更需要持续的局部脓肿引流，其中血糖控制差的患者继发血流感染(bloodstream infections，BSI)的比率更高。共获得HvKP菌株219株，K1/K2血清型占总数81.7%，K2型患者发生BSI的比率高于K1型。PCR检测结果表明，毒力基因(rmpA、areo、kfu、allS、iroN、magA、uge、wcaG)在K1/K2型菌株的携带率明显高于non-K1/K2型，ST23和ST65是最常见的多位点序列分型(multilocus sequence typing, MLST)，分别属于K1及K2血清型。另外收集35株经典肺炎克雷伯菌(classic Klebsiella pneumoniae，cKP)，其血清分型主要以非K1/K2型为主。HvKP的毒力基因携带率及黏性程度明显高于cKP，前者造成的原发性肝脓肿患者易出现多组织器官感染，但对除氨苄西林以外的临床常用抗菌药物表现出更高敏感性，经过有效的治疗，患者的总体预后较好。本研究对社区获得性高毒肺炎克雷伯菌的病原学特征进行分析，并结合患者临床特征进行阐述，可对临床及科研工作起到一定参考价值。.

This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp).
Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.
Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.
In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.

Hypervirulent Klebsiella pneumoniae (hvKP) has emerged as a novel variant of K. pneumoniae, exhibiting distinct phenotypic and genotypic characteristics that confer increased virulence and pathogenicity. It is not only responsible for nosocomial infections but also community-acquired infections, including liver abscesses, endophthalmitis, and meningitis, leading to significant morbidity and mortality. HvKP has been reported all over the world, but it is mainly prevalent in Asia Pacific, especially China. Moreover, hvKP can acquire carbapenemase genes resulting in the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), which possesses both high virulence and drug resistance capabilities. Consequently, CR-hvKP poses substantial challenges to infection control and presents serious threats to global public health. In this paper, we provide a comprehensive summary of the epidemiological characteristics, virulence factors, and mechanisms underlying carbapenem resistance in hvKP strains with the aim of offering valuable insights for practical prevention strategies as well as future research.

UNASSIGNED: Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications.
UNASSIGNED: We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms.
UNASSIGNED: Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, differing from those of cKP.
UNASSIGNED: This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.

Hypervirulent Klebsiella pneumoniae remains a significant global public health concern, characterized by a unique syndrome involving monomicrobial primary pyogenic liver abscesses, often leading to metastatic complications such as endophthalmitis, meningitis, and other infections. These infections are frequently observed in immunocompetent hosts or diabetic patients, particularly those of Asian ethnicity. In this report, we present the case of a 66-year-old Burmese female, currently residing in the United States, who presented with severe swelling, pain, discharge, and vision loss in her left eye, along with abdominal pain. Subsequent investigation revealed monomicrobial Klebsiella pneumoniae acute cholecystitis with an adjacent liver abscess, complicated by bacteremia, endogenous endophthalmitis, and portal vein thrombosis. Treatment with ceftriaxone proved successful in addressing her intra-abdominal infections, while anticoagulation therapy was initiated following multidisciplinary discussions among all involved subspecialties. Early diagnosis and the timely administration of appropriate treatment are crucial in reducing mortality and preventing further complications.

BACKGROUND: The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp.
METHODS: Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23.
RESULTS: A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including blaNDM-1, dfrA14 and qnrS1. Importantly, blaNDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline.
CONCLUSIONS: The emergence of blaNDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.