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Sun H, Zhang H, Lai W, Lei L, Li J, Chen M, Li H, Zhao Z. Clinical and microbiological characteristics and prognosis of invasive infection caused by Klebsiella pneumoniae in the community. Ann Med 2025; 57:2450526. [PMID: 39797408 PMCID: PMC11727050 DOI: 10.1080/07853890.2025.2450526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/09/2024] [Accepted: 12/12/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND The incidence of invasive infection of Klebsiella pneumoniae (Kp) in the community is increasing every year, and the high disability and mortality rates associated with them pose great challenges in clinical practice. This study aimed to explore the clinical and microbiological characteristics of Kp invasive infection in the community. METHOD This study investigated the data of 291 patients with Kp infection in the community in three hospitals (Zhongshan City, Guangdong Province) from January 2020 to August 2023. The risk factors for invasive infection and death due to Kp infection were determined through multivariate logistic regression models and Cox models. RESULT The mortality rate of community-acquired Klebsiella pneumoniae (cKp) invasive infections markedly exceeded that for non-invasive infections (47.6% vs 25.9%) (p = 0.001). Multivariate logistic regression analysis identified high viscosity type (OR:2.26, p = 0.031) and shock (OR:3.42, p = 0.001) as significant risk factors for invasive infection. Among patients who succumbed to invasive infections, multivariate Cox regression analysis revealed that elevated CK-MB (OR: 1.01, p = 0.040), increased IL-6 levels (OR: 1.00, p = 0.023), and high SOFA scores (OR: 1.16, p = 0.017) were linked to increased mortality risk. This study found that co-infection of the liver, lungs, and bloodstream was most prevalent in invasive infections. Notably, co-infection involving the lungs, bloodstream, and brain was associated with the highest mortality rate (100%, 6/6). No significant differences were found between patients with or without invasive infections, as well as between surviving and non-surviving patients (all p ≥ 0.05). CONCLUSION Patients with cKp invasive infections exhibit more severe inflammatory responses and a poorer prognosis, necessitating vigilant attention from clinicians. The treatment of cKp invasive infections remains inconclusive between "heavy-handed strikes" and "sensitivity is sufficient". Focusing solely on the liver and lungs while neglecting infection sites outside of these organs can lead to catastrophic results, which should be avoided during treatment.
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Affiliation(s)
- Hongkui Sun
- Critical care department, Zhongshan City People’s Hospital, Guangdong Province, China
| | - Hanlin Zhang
- General Medicine Department, Zhongshan Minzhong Hospital, Guangdong Province, China
| | - Wenqing Lai
- Critical care department, Zhongshan City People’s Hospital, Guangdong Province, China
| | - Li Lei
- Department of respiratory medicine, Zhongshan City People’s Hospital, Guangdong Province, China
| | - Jianwei Li
- Critical care department, Zhongshan City People’s Hospital, Guangdong Province, China
| | - Miaolian Chen
- Critical care department, Zhongshan City People’s Hospital, Guangdong Province, China
| | - Haijun Li
- Department of Reproductive Medicine, Zhongshan Boai Hospital, Guangdong Province, China
| | - Zhanyuan Zhao
- Critical care department, Zhongshan City People’s Hospital, Guangdong Province, China
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2
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Thomsen ME, Bennike TB, Christiansen G, Emmersen J, Laursen NS, Zarantonello A, Andersen GR, Liu L, Dueholm MKD, Opstrup KV, Stensballe A, Birkelund S. Differences in complement activation of serum-resistant and serum-sensitive Klebsiella pneumoniae isolates. Mol Immunol 2025; 183:274-285. [PMID: 40424786 DOI: 10.1016/j.molimm.2025.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/27/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025]
Abstract
The gram-negative bacteria Klebsiella pneumoniae are genetically heterogeneous and a common cause of sepsis and bacteremia in humans. The complement system is the first line of defence against bacteria when they invade the body. We previously investigated K. pneumoniae isolates from sepsis patients. We found that complement factor (C) 3 is deposited on all isolates independent of serum sensitivity, but the membrane attack complex (MAC) was only formed on the serum-sensitive isolates. To investigate the mechanism for serum resistance, we incubated one serum-sensitive and one serum-resistant isolate in human serum and identified bound complement factors by mass spectrometry. The serum-sensitive isolate had all expected complement factors bound, including C4, while the serum-resistant isolate had only C3 bound. The serum resistance was caused by a fast cleavage of C3b to iC3b. Thereby, the C5 convertase, and thus MAC, cannot be formed. To confirm the role of C4 in serum sensitivity, C4 was inhibited by the nanobody hC4Nb8, resulting in the survival of the serum-sensitive isolate. This suggests that C4 is indispensable for MAC formation through the classical and lectin pathways. In contrast, when activated selectively, the alternative pathway primarily leads to the generation of iC3b, thereby enabling serum resistance by bypassing MAC assembly.
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Affiliation(s)
- Mikkel Eggert Thomsen
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
| | - Tue Bjerg Bennike
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
| | - Gunna Christiansen
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
| | - Jeppe Emmersen
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
| | | | - Alessandra Zarantonello
- Biotech Research & Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen DK-2200, Denmark.
| | - Gregers Rom Andersen
- Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, Aarhus C 8000, Denmark.
| | - Lei Liu
- Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, Aalborg Ø 9220, Denmark.
| | - Morten Kam Dahl Dueholm
- Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, Aalborg Ø 9220, Denmark.
| | - Katharina V Opstrup
- Danish Veterinary and Food Administration, Stationsparken 31-33, Glostrup 2600, Denmark.
| | - Allan Stensballe
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
| | - Svend Birkelund
- Department of Health Science and Technology, Medical Microbiology and Immunology, Aalborg University, Selma Lagerløfs Vej 249, Gistrup 9260, Denmark.
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DeLeo FR, Freedman B, Porter AR, Opoku-Temeng C, Kobayashi SD, Chen L, Kreiswirth BN. Evaluation of capsule polysaccharide (CPS)-specific antibodies for broad recognition of prominent multidrug-resistant Klebsiella pneumoniae. Microbiol Spectr 2025:e0333824. [PMID: 40401961 DOI: 10.1128/spectrum.03338-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 04/24/2025] [Indexed: 05/23/2025] Open
Abstract
Klebsiella pneumoniae is primarily an opportunistic pathogen known for causing healthcare-associated infections in individuals with significant risk factors and comorbidities. These bacteria are typically multidrug-resistant (MDR), a phenotype conferred in part by the production of extended-spectrum beta-lactamases and/or carbapenemases. By comparison, so-called hypervirulent K. pneumoniae (hvKp) are defined by their ability to cause severe community-acquired infections in otherwise healthy individuals. Although hvKp lineages have historically not been MDR, there has been a recent emergence of strains with both hypervirulence and multidrug resistance phenotypes. Treatment of infections caused by MDR K. pneumoniae can be difficult, and new preventative measures are needed. As a step toward the development of a vaccine directed to prevent or moderate infections caused by these pathogens, we tested the ability of capsule polysaccharide (CPS) derived from eight selected K. pneumoniae capsule types (KLs) to elicit rabbit antibodies that recognize important KLs isolated from human infections. Seventy-one out of 84 (84.5%) contemporary K. pneumoniae clinical isolates tested were recognized by CPS-specific rabbit antisera. There was the unexpected binding of the antibodies to some isolates with KLs not included in the CPS-antigen cocktails. Notably, rabbit IgG purified from CPS-specific antisera promoted and/or enhanced human PMN bactericidal activity toward all but one of the selected clinical isolates that were not killed by PMNs outright (in the absence of specific antibody). These data provide support to the idea that a CPS-antigen cocktail could be developed to protect against the K. pneumoniae KLs that are the most frequent cause of human infections.IMPORTANCEKlebsiella pneumoniae is among the leading causes of death by infectious agents. Many of the prominent K. pneumoniae lineages are resistant to multiple classes of antibiotics, and options for treatment are limited. New countermeasures that prevent infections are needed. Here we tested the ability of capsule polysaccharide (CPS) antigen mixtures (or cocktails) to elicit rabbit antibodies that recognize K. pneumoniae from a large collection of extended-spectrum beta-lactamase-producing clinical isolates. Importantly, these antibodies had the ability to promote opsonophagocytic killing by human PMNs. Our results provide proof-of-concept for a CPS vaccine cocktail approach that could be developed to prevent infections caused by the most important K. pneumoniae lineages.
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Affiliation(s)
- Frank R DeLeo
- Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Brett Freedman
- Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Adeline R Porter
- Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Clement Opoku-Temeng
- Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Scott D Kobayashi
- Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Liang Chen
- Division of Clinical and Translational Therapeutics, Department of Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA
| | - Barry N Kreiswirth
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA
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Hetta HF, Alanazi FE, Ali MAS, Alatawi AD, Aljohani HM, Ahmed R, Alansari NA, Alkhathami FM, Albogmi A, Alharbi BM, Alanzi HS, Alaqyli AB, Ramadan YN. Hypervirulent Klebsiella pneumoniae: Insights into Virulence, Antibiotic Resistance, and Fight Strategies Against a Superbug. Pharmaceuticals (Basel) 2025; 18:724. [PMID: 40430542 PMCID: PMC12115101 DOI: 10.3390/ph18050724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2025] [Revised: 05/12/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
Community-acquired infections caused by Klebsiella pneumoniae (K. pneumoniae) have become a significant global health concern, particularly with the emergence of hypervirulent strains (hvKP). These strains are associated with severe infections, such as pyogenic liver abscesses, even in otherwise healthy individuals. Initially reported in Taiwan in the 1980s, hvKP has now spread worldwide. The pathogenicity of hvKP is attributed to an array of virulence factors that enhance its ability to colonize and evade host immune defenses. Additionally, the convergence of hypervirulence with antibiotic resistance has further complicated treatment strategies. As a member of the ESKAPE group of pathogens, K. pneumoniae exhibits high resistance to multiple antibiotics, posing a challenge for healthcare settings. This review provides a comprehensive overview of hvKP, highlighting its structural and pathogenic differences from classical K. pneumoniae strains, key virulence factors, mechanisms of antibiotic resistance, and the increasing threat of multidrug-resistant hvKP. Lastly, we discuss current treatment guidelines and emerging therapeutic strategies to combat this formidable pathogen.
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Affiliation(s)
- Helal F. Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia;
| | - Fawaz E. Alanazi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia;
| | - Mostafa A. Sayed Ali
- Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia;
| | - Ahmed D. Alatawi
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia;
| | - Hashim M. Aljohani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madina 41477, Saudi Arabia;
- Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Rehab Ahmed
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia;
| | - Nuha A. Alansari
- Laboratory Medicine, College of Applied Medical Sciences, Umm Al-Qura University, Jeddah 22231, Saudi Arabia;
| | - Fahad M. Alkhathami
- College of Applied Medical Sciences, University of Tabuk, Tabuk 47315, Saudi Arabia; (F.M.A.); (H.S.A.); (A.B.A.)
| | - Alaa Albogmi
- Medical Laboratory Technology, King Abdulaziz University, Jeddah 80216, Saudi Arabia;
| | - Bander M. Alharbi
- Medical Laboratory Technology, College of Applied Medical Sciences, University of Tabuk, Tabuk 47524, Saudi Arabia;
| | - Hanadi S. Alanzi
- College of Applied Medical Sciences, University of Tabuk, Tabuk 47315, Saudi Arabia; (F.M.A.); (H.S.A.); (A.B.A.)
| | - Amirah B. Alaqyli
- College of Applied Medical Sciences, University of Tabuk, Tabuk 47315, Saudi Arabia; (F.M.A.); (H.S.A.); (A.B.A.)
| | - Yasmin N. Ramadan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt;
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Ali HR, Valdivia C, Negus D. Bacteriophage-embedded and coated alginate layers inhibit biofilm formation by clinical strains of Klebsiella pneumoniae. J Appl Microbiol 2025; 136:lxaf099. [PMID: 40268347 DOI: 10.1093/jambio/lxaf099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 03/28/2025] [Accepted: 04/22/2025] [Indexed: 04/25/2025]
Abstract
AIMS This study aimed to determine the antibiofilm properties of Klebsiella pneumoniae phages previously isolated from Thai hospital sewage water. Furthermore, we aimed to develop a phage-embedded and coated alginate hydrogel, suitable as a wound dressing or surface coating to prevent K. pneumoniae proliferation and biofilm formation. METHODS AND RESULTS The biofilm forming capacity of six clinical K. pneumoniae isolates was determined by means of the crystal violet assay and four strains which exhibited strong adherence were selected for further characterization. Two phages (vB_KpnA_GBH014 and vB_KpnM_GBH019) were found to both significantly prevent (P = <0.0005) and disrupt (P = <0.05) biofilms produced by their K. pneumoniae hosts as determined by optical density readings using the crystal violet assay. Furthermore, alginate layers embedded and coated with phages vB_KpnA_GBH014 and vB_KpnM_GBH019 produced antibiofilm surfaces. Viable counts of recovered biofilms showed that alginate hydrogels containing phage vB_KpnA_GBH014 or vB_KpnM_GBH019 were associated with significantly fewer K. pneumoniae vs. no-phage controls (1.61 × 108 cfu ml-1 vs. 1.67 × 104 cfu ml-1, P = <0.005 and 1.78 × 108 cfu ml-1 vs. 6.11 × 102 cfu ml-1, P = <0.00005, respectively). Confocal microscopy further revealed a significant reduction in the biovolume of biofilms formed on phage embedded and coated alginate hydrogels compared to no-phage controls. CONCLUSIONS Phages vB_KpnA_GBH014 and vB_KpnM_GBH019 can both prevent and disrupt biofilms produced by clinical isolates of K. pneumoniae. Embedding and coating these phages into alginate produces an antibiofilm matrix which may have promise for coating medical devices or as a wound dressing.
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Affiliation(s)
- Hala R Ali
- Department of Biosciences, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom
- Animal Health Research Institute, Agriculture Research Centre, Bacteriology Department, Dokki, Giza 12618, Egypt
| | - Carlos Valdivia
- Institute for Integrative Systems Biology, University of Valencia-CSIC, Paterna 46980, Spain
| | - David Negus
- Department of Biosciences, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, United Kingdom
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6
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Yang Y, McNally A, Zong Z. Call for prudent use of the term hypervirulence in carbapenem-resistant Klebsiella pneumoniae. THE LANCET. MICROBE 2025; 6:101090. [PMID: 39993405 DOI: 10.1016/j.lanmic.2025.101090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 01/27/2025] [Indexed: 02/26/2025]
Affiliation(s)
- Yongqiang Yang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Pathogen Research, West China Hospital, Sichuan University, Chengdu 610041, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China
| | - Alan McNally
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Zhiyong Zong
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Pathogen Research, West China Hospital, Sichuan University, Chengdu 610041, China; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China.
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Zeynali Kelishomi F, Amereh S, Ghayyaz F, Kazemzadeh Anari R, Khanjani S, Nikkhahi F. Antimicrobial Resistance Patterns and Virulence Gene Profiles of Klebsiella pneumoniae Isolated from Surgical Site Infections in Iran. Surg Infect (Larchmt) 2025. [PMID: 40296852 DOI: 10.1089/sur.2024.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025] Open
Abstract
Background: The prevalence of Klebsiella pneumoniae in surgical site infections (SSIs) has increased recently. This study aimed to evaluate the antimicrobial resistance patterns and biofilm formation capacity of K. pneumoniae strains isolated from SSIs. Methods: A total of 63 K. pneumoniae isolates were obtained from patients with SSIs. Antimicrobial susceptibility testing was determined using the Kirby-Bauer method. Molecular analyses were performed to confirm the presence of virulence and antibiotic resistance genes. Biofilm formation was determined using a semiquantified microtiter plate assay, and optical density measurements were used to classify the isolates into weak, moderate, and strong biofilm producers. Biofilm structure was observed using field-emission scanning electron microscopy. Statistical analyses were performed using SPSS software version 16 (SPSS Inc., Chicago, IL, USA), and data were analyzed and presented in terms of frequency and percentage. Results: The frequencies of fimH, mrkD, mrkA, wcaG, and magA were 98.4%, 96.8%, 77.7%, 61.9%, and 7.9%, respectively. The highest rates of antibiotic resistance were observed for cefazolin, cefuroxime, and piperacillin/tazobactam and 98.4% of the isolates were resistant to at least one antibiotic agent. The most prevalent resistance genes were blaSHV (42.8%), blaCTX-M (31.7%), blaTEM (28.5%), and blaOXA48 (22.2%). All the tested isolates were able to produce biofilms, and 76.2% were classified as strong biofilm producers. Conclusions: Klebsiella pneumoniae is one of the common pathogens in SSIs, and due to its antibiotic resistance and the presence of multiple virulence factors, proper controlling strategies need to be carried out.
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Affiliation(s)
| | - Samira Amereh
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Fatemeh Ghayyaz
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Raana Kazemzadeh Anari
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Susan Khanjani
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Farhad Nikkhahi
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
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Ohno T, Harada S, Saito H, Tanii R, Komori K, Kurosawa M, Wakatake H, Kanazawa M, Ohki U, Minoura A, Yamada M, Kaneko S, Anzai M, Tsutsui Y, Kuhara A, Oyanagi T, Tanaka Y, Takemura H, Takeuchi H, Kunishima H. Molecular epidemiology and clinical features of Klebsiella variicola bloodstream infection compared with infection with other Klebsiella pneumoniae species complex strains. Microbiol Spectr 2025:e0301724. [PMID: 40277351 DOI: 10.1128/spectrum.03017-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/29/2025] [Indexed: 04/26/2025] Open
Abstract
Klebsiella variicola is an emerging pathogen within the Klebsiella pneumoniae species complex, and its clinical and microbiological characteristics remain poorly understood. This retrospective case-control study analyzed 252 patients with bloodstream infections caused by K. pneumoniae species complex, including 60 with K. variicola infection, to elucidate these characteristics. Our study showed no significant differences in clinical outcomes, such as 30-day mortality, between K. variicola and K. pneumoniae. However, a significant difference was found in the rate of harboring [peg-344, iucA, and rmpA] genes, which are associated with virulence in K. pneumoniae, suggesting that K. variicola may be generally less virulent. Notably, we identified two patients with community-acquired liver abscess caused by hypervirulent K. variicola, representing the first genetically analyzed case of this phenomenon in Japan and highlighting the potential virulence of this species. While there have been several reports on K. variicola carrying hypervirulence genes, this is the first report in Japan, to our knowledge, to genetically characterize a hypervirulent K. variicola isolated from a patient with disseminated liver abscesses using whole-genome sequencing. Multilocus sequence typing revealed high diversity among K. variicola isolates, with 49 distinct sequence types identified, 30 of which were newly registered, highlighting the genetic heterogeneity of this pathogen. No significant clinical differences were observed between K. variicola and other Klebsiella spp. The emergence of hypervirulent K. variicola strains with the potential to cause severe complications warrants further surveillance and research. IMPORTANCE Klebsiella variicola is increasingly recognized as an emerging pathogen commonly found in the environment and human gut. However, its clinical and microbiological characteristics remain poorly understood. This study provides a comprehensive analysis of K. variicola bloodstream infections (BSIs), comparing clinical and genetic features with the closely related K. pneumoniae. We identified significant differences in the prevalence of virulence genes between the two species. Notably, we observed K. variicola causing disseminated liver abscesses, similar to hypervirulent K. pneumoniae strains. These findings have important implications for accurate species identification, informing treatment strategies, and improving patient outcomes in the face of this emerging infectious threat.
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Affiliation(s)
- Tatsuya Ohno
- Department of Clinical Laboratory, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, Kouzunomori, Narita, Japan
| | - Sohei Harada
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan
| | - Hiroki Saito
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Rimi Tanii
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Kohji Komori
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan
| | - Miki Kurosawa
- Department of Clinical Laboratory Technology, St. Marianna University Hospital, Kawasaki, Kanagawa, Japan
| | - Haruaki Wakatake
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Minoru Kanazawa
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Uiri Ohki
- Division of Cardiovascular Medicine Saitama Medical Center, Jichi Medical University, Omiya-ku, Saitama, Japan
| | - Ayu Minoura
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Mario Yamada
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Satsuki Kaneko
- Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Momoko Anzai
- Department of Clinical Laboratory, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
| | - Yuto Tsutsui
- Department of Clinical Laboratory, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
| | - Asuka Kuhara
- Department of Nursing, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
| | - Tadatomo Oyanagi
- Department of Clinical Laboratory Technology, St. Marianna University Hospital, Kawasaki, Kanagawa, Japan
| | - Yosuke Tanaka
- Department of Clinical Laboratory, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
| | - Hiromu Takemura
- Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Hiroaki Takeuchi
- Department of Medical Laboratory Sciences, Health and Sciences, International University of Health and Welfare Graduate School, Kouzunomori, Narita, Japan
| | - Hiroyuki Kunishima
- Department of Infection diseases, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
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Mba IE, Mba TO, Uwazie CK, Aina FA, Kemisola AO, Uwazie IJ. New insights and perspectives on the virulence of hypervirulent Klebsiella pneumoniae. Folia Microbiol (Praha) 2025:10.1007/s12223-025-01261-9. [PMID: 40198504 DOI: 10.1007/s12223-025-01261-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 03/16/2025] [Indexed: 04/10/2025]
Abstract
Klebsiella pneumoniae, a Gram-negative bacterium, comprises strains with diverse virulence potentials, ranging from classical to hypervirulent variants. Understanding the genetic basis underlying the virulence disparities between hypervirulent (hvKp) and classical K. pneumoniae (cKp) strains is crucial. hvKp strains are characterized by hypermucoviscosity, attributed to the presence of specific virulence genes and the production of molecules that aid in their ability to survive, evade host immune defenses, and cause infection. In contrast, classical strains exhibit a broader array of antimicrobial resistance determinants, conferring resistance to multiple antibiotics. Although current definitions of hvKp incorporate clinical features, phenotypes, and genotypes, identifying hvKp strains in clinical settings remains challenging. Genomic studies have been pivotal and have helped to identify distinct genetic profiles in hvKp strains, including unique virulence plasmids and chromosomal variations, underscoring the genetic diversity within K. pneumoniae populations. This review examines the virulence and genetic determinants associated with hvKp. The presence of genes defining hypervirulence, alongside considerations of their utility as biomarkers and targets for therapeutic strategies, is discussed, while also providing insight into biofilm formation by hvKp and key questions that need urgent responses in understanding hvKp.
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Affiliation(s)
- Ifeanyi Elibe Mba
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan, Ibadan, 200005, Nigeria.
- Department of Microbiology, Faculty of Biological Sciences, University of Nigeria Nsukka, Enugu, 410001, Nigeria.
| | - Toluwalase Odunayo Mba
- Department of Public Health, Faculty of Basic Medical and Health Sciences, Lead City University, Ibadan, 200255, Nigeria
- Medical Institute, Sumy State University, Sumy, 40007, Ukraine
| | | | - Fetuata Aminat Aina
- Department of Microbiology, College of Natural Sciences, Federal University of Agriculture, Abeokuta, 111101, Nigeria
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Nagendra D, Chaudhuri S, Gupta N, Shanbhag V, Eshwara VK, Rao S, Varma M, Srinivas T, Todur P, Priya PS, Bhat VR. Prevalence, Risk Factors, and Clinical Outcomes of Hypervirulent Klebsiella pneumoniae Strains among Klebsiella pneumoniae Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2025; 29:370-393. [PMID: 40322229 PMCID: PMC12045058 DOI: 10.5005/jp-journals-10071-24957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 03/19/2025] [Indexed: 05/08/2025] Open
Abstract
Aim and background Hypervirulent Klebsiella pneumoniae (HvKp) is a virulent strain associated with invasive infections. While initially community-acquired, hospital-acquired HvKp (HA-HvKp) and carbapenem-resistant HvKp (CR-HvKp) are increasingly reported. This meta-analysis evaluates the prevalence, risk factors, and clinical outcomes associated with HvKp, including CR-HvKp and HA-HvKp, among Kp infections. Methodology A systematic search of PubMed, Scopus, Embase, and Cochrane Library was conducted until December 2024. Observational studies comparing HvKp vs classical Kp (cKp), CR-HvKp vs carbapenem-sensitive HvKp (CS-HvKp), and HA-HvKp vs community-acquired HvKp (CA-HvKp) were included. Quality was assessed using the Joanna Briggs Critical Appraisal Tool, and pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results Fifty studies with 6,663 participants were included. The HvKp prevalence was 33.0%, with most studies from Asia, predominantly China. Temporal analysis revealed an increase in HvKp prevalence (27.7% in 2006-2018 to 38.5% in 2019-2024). The CR-HvKp prevalence rose from 9.5% to 16.5% (2016-2024). The HA-HvKp prevalence increased from 25.9 to 47.1%. Key risk factors included diabetes mellitus (OR = 1.56), CA-Kp (OR = 2.59), and hypermucoviscous (HM)-phenotype (OR = 29.79). Complications included liver abscess (OR = 6.35), metastatic spread (OR = 4.74), meningitis (OR = 11.14), and septic shock (OR = 1.30). Mortality was higher in HvKp infections but not statistically significant (p = 0.219). HA-HvKp and immunosuppression were significant CR-HvKp risk factors, with CR-HvKp showing higher mortality. Conclusions Diabetes mellitus, CA-Kp infections, and HM-phenotype are significant risk factors for HvKp. The rising prevalence of CR-HvKp and HA-HvKp highlights the need for early detection, infection control, and targeted treatment strategies. How to cite this article Nagendra D, Chaudhuri S, Gupta N, Shanbhag V, Eshwara VK, Rao S, et al. Prevalence, Risk Factors, and Clinical Outcomes of Hypervirulent Klebsiella pneumoniae Strains among Klebsiella pneumoniae Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2025;29(4):370-393.
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Affiliation(s)
- Danavath Nagendra
- Department of Critical Care, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Souvik Chaudhuri
- Department of Critical Care, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Nitin Gupta
- Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Vishal Shanbhag
- Department of Critical Care, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Vandana K Eshwara
- Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shwethapriya Rao
- Department of Critical Care, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Muralidhar Varma
- Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Thejesh Srinivas
- Department of Critical Care, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Pratibha Todur
- Department of Respiratory Therapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - PS Priya
- Department of Radiodiagnosis and Imaging, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Vinutha R Bhat
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Uemura K, Sato T, Yamamoto S, Ogasawara N, Toyting J, Aoki K, Takasawa A, Koyama M, Saito A, Wada T, Okada K, Yoshida Y, Kuronuma K, Nakajima C, Suzuki Y, Horiuchi M, Takano K, Takahashi S, Chiba H, Yokota SI. Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae. Nat Commun 2025; 16:2917. [PMID: 40133255 PMCID: PMC11937256 DOI: 10.1038/s41467-025-58049-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/11/2025] [Indexed: 03/27/2025] Open
Abstract
Bacteria continually evolve. Previous studies have evaluated bacterial evolution in retrospect, but this approach is based on only speculation. Cohort studies are reliable but require a long duration. Additionally, identifying which genetic mutations that have emerged during bacterial evolution possess functions of interest to researchers is an exceptionally challenging task. Here, we establish a Rapid and Integrated Bacterial Evolution Analysis (RIBEA) based on serial passaging experiments using hypermutable strains, whole-genome and transposon-directed sequencing, and in vivo evaluations to monitor bacterial evolution in a cohort for one month. RIBEA reveals bacterial factors contributing to serum and antimicrobial resistance by identifying gene mutations that occurred during evolution in the major respiratory pathogen Klebsiella pneumoniae. RIBEA also enables the evaluation of the risk for the progression and the development of invasive ability from the lung to blood and antimicrobial resistance. Our results demonstrate that RIBEA enables the observation of bacterial evolution and the prediction and identification of clinically relevant high-risk bacterial strains, clarifying the associated pathogenicity and the development of antimicrobial resistance at genetic mutation level.
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Affiliation(s)
- Kojiro Uemura
- Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
- Department of Respiratory Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Toyotaka Sato
- Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
- Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan.
- Graduate School of Infectious Diseases, Hokkaido University, Kita-Ku, Sapporo, Japan.
- One Health Research Center, Hokkaido University, Kita-Ku, Sapporo, Japan.
- Veterinary Research Unit, International Institute for Zoonosis Control, Sapporo, University, Kita-Ku, Sapporo, Japan.
| | - Soh Yamamoto
- Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Noriko Ogasawara
- Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Jirachaya Toyting
- Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan
| | - Kotaro Aoki
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, Japan
| | - Akira Takasawa
- Department of Pathology, Asahikawa Medical University, Asahikawa, Japan
| | - Masayuki Koyama
- Department of Public Health, Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Atsushi Saito
- Department of Respiratory Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Takayuki Wada
- Graduate School of Human Life and Ecology, Osaka Metropolitan University, 3-3-138, Sugimoto, Sumiyoshi-ku, Osaka, Japan
- Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-2-7-601, Asahimachi, Abeno-ku, Osaka, Japan
| | - Kaho Okada
- Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan
| | - Yurie Yoshida
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Koji Kuronuma
- Department of Respiratory Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Chie Nakajima
- Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, N20, Kita-Ku, Sapporo, Japan
- International Collaboration Unit, Hokkaido University, International Institute for Zoonosis Control, Kita-Ku, Sapporo, Japan
- Hokkaido University, Institute for Vaccine Research and Development (HU-IVReD), Kita-Ku, Sapporo, Japan
| | - Yasuhiko Suzuki
- Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, N20, Kita-Ku, Sapporo, Japan
- International Collaboration Unit, Hokkaido University, International Institute for Zoonosis Control, Kita-Ku, Sapporo, Japan
- Hokkaido University, Institute for Vaccine Research and Development (HU-IVReD), Kita-Ku, Sapporo, Japan
| | - Motohiro Horiuchi
- Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan
- Graduate School of Infectious Diseases, Hokkaido University, Kita-Ku, Sapporo, Japan
- One Health Research Center, Hokkaido University, Kita-Ku, Sapporo, Japan
| | - Kenichi Takano
- Veterinary Research Unit, International Institute for Zoonosis Control, Sapporo, University, Kita-Ku, Sapporo, Japan
| | - Satoshi Takahashi
- Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Chuo-Ku, Sapporo, Japan
| | - Hirofumi Chiba
- Department of Respiratory Medicine, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
| | - Shin-Ichi Yokota
- Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan
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Li Y, Tang S, Han Q, Xia P, Si T, Song Y, Xia Y. The investigation of molecular epidemiological characteristics and resistance mechanism of tigecycline resistant Klebsiella pneumoniae from a large teaching hospital in southwest China, Chongqing. Front Cell Infect Microbiol 2025; 15:1540967. [PMID: 40182765 PMCID: PMC11965929 DOI: 10.3389/fcimb.2025.1540967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/21/2025] [Indexed: 04/05/2025] Open
Abstract
Background Klebsiella pneumoniae is one of the main pathogens of nosocomial infection, among which carbapenems can be used for multidrug-resistant Klebsiella pneumoniae. However, in the past decade, the resistance rate of carbapenem-resistant Klebsiella pneumoniae has increased yearly. Tigecycline has good antibacterial activity in treating severe bacterial infections, but the reports of tigecycline resistance are increasing. This study aimed to investigate the mechanism of drug resistance and epidemiological characteristics of tigecycline-resistant Klebsiella pneumoniae (TRKP) in a large teaching hospital in southwest China, Chongqing. Methods We isolated 30 TRKP strains from this hospital between August 2021 and December 2023. By PCR and sequencing, we examined the presence and mutation rates of genes associated with tigecycline resistance, including acrR, oqxR, ramR, tmexC, tet(x), tet(A), tet(L), and rpsj, and performed efflux pump inhibition experiments to verify efflux pump activity. At the same time, real-time RT-PCR was used to detect the expression levels of efflux pump genes (acrB and oqxB) and ramA. To investigate the prevalence trend of TRKP in our hospital, we performed multi-site sequence typing (MLST) analysis. Results The mutation rates of ramR (73.3%) and tet(A) (63.3%) were significant. In efflux pump inhibition experiments, PaβN could reverse the resistance of 29 TRKP strains (96.7%) to tigecycline. Real-time RT-PCR results showed that acrB and ramA genes were up-regulated in 22 strains, while oqxB genes were overexpressed in only 4 strains. MLST analysis showed that these strains could be divided into 25 different ST subtypes, indicating that no outbreak of TRKP occurred in our hospital. In addition, two tmexCD-torpj positive strains, ST661 and ST1561, were identified for the first time. Conclusion The efflux pump acrB and tet(A) mutations are the primary mechanisms of resistance to tigecycline-resistant Klebsiella pneumoniae at our hospital. The ramR mutation can mediate efflux pump activity of acrB by up-regulating ramA overexpression.
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Affiliation(s)
| | | | | | | | | | | | - Yun Xia
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical
University, Chongqing, China
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13
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Tsombou FM, Al Dhanhani ASS, Alhmoudi AMSA, Al Hmoudi MASM, Ridouane FL, Alabdouli MFA, Alhammadi HJ, Alsamahi MEAA, Mirza SB. Altitudinal influence on survival mechanisms, nutritional composition, and antimicrobial activity of Moringa Peregrina in the summer climate of Fujairah, UAE. Sci Rep 2025; 15:5635. [PMID: 39955360 PMCID: PMC11829955 DOI: 10.1038/s41598-025-90223-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 02/11/2025] [Indexed: 02/17/2025] Open
Abstract
Extreme environments significantly impact the metabolic profiles of plants, leading to variations in chemical composition and bioactivity. This study investigates the effects of altitude, plant part age, and light exposure on the chemical composition and antimicrobial properties of Moringa peregrina. Based on our results, mineral contents were plant location dependent; while dry matter, ash, total digestible nutrients (TDN), fibre, protein, and tannins, were greater in the samples from the mountain. Vitamin E was more concentrated in the wadi. Vitamin A, selenium, phenols, and heavy metals were undetectable in both environments. Antimicrobial assays revealed stronger activity in mountain samples than the other locations. Age-dependent analyses showed that nitrogen, protein, ash, and electrolyte leakage were higher in young plant parts, whereas chlorophyll a and b levels were elevated in mature leaves and younger branches, particularly in lower elevations. Interestingly, young leaves from mountain regions had higher chlorophyll concentrations compared to mature leaves, contrasting with trends at other elevations. Photosynthetic photon flux density (PPFD) measurements were also highest in the mountain region. These findings suggest that M. peregrina employs diverse metabolic adaptations for survival in challenging environments, potentially offering socioeconomic value to indigenous communities through its bioactive properties.
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Affiliation(s)
| | | | | | | | | | - Maitha Fahad Ahmed Alabdouli
- Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates
- University of Sharjah, Sharjah, United Arab Emirates
| | - Hessa Jassim Alhammadi
- Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates
- University of Sharjah, Sharjah, United Arab Emirates
| | - Mozah Ebraheim Abdulla Ali Alsamahi
- Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates
- American University of Ras Al Khaimah, Ras Al Khaimah, United Arab Emirates
| | - Shaher Bano Mirza
- Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates.
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14
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Rosa JN, da Silva GC, Fontes PP, Guidini MM, Oliveira RP, Bazzolli DMS. Klebsiella spp. in healthy pigs: reservoirs of antimicrobial resistance and potential pathogenic threats. J Appl Microbiol 2025; 136:lxaf029. [PMID: 39919758 DOI: 10.1093/jambio/lxaf029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/15/2024] [Accepted: 02/06/2025] [Indexed: 02/09/2025]
Abstract
AIM The aim of this study was to isolate Klebsiella spp. from clinically healthy animals fed diets with or without antimicrobial growth promoters (AGP). Additionally, the study evaluated whether the inclusion of growth promoters affected the recovery of multi-drug-resistant isolates. METHODS AND RESULTS A total of 144 isolates were obtained from rectal swabs on Simmons citrate agar supplemented with 1% inositol. Of these, 45 non-replicative isolates underwent extensive characterization, including molecular and phenotypic analyses. Sequencing identified that 77% were Klebsiella pneumoniae, 14.5% K. aerogenes, and 8.5% K. variicola. Isolates exhibiting the same polymorphic profiles were detected across different animals and treatments, with and without AGP. Seventy-one percent were multidrug-resistant, as determined by disk diffusion testing. The isolates harbored genes such as mcr-1, blaCTX-M-2, sul2, tetB, qnrS, and dfrA, among others. Additionally, genes encoding siderophores like enterobactin, aerobactin, and yersiniabactin were detected via Polymerase Chain Reaction (PCR). Thirty-nine isolates were strong biofilm producers, 45% moderate, and 16% weak in vitro tests. The predominant genetic profiles included single, double, or triple-locus variants of ST25, ST147, and ST4691. Two novel sequence types were identified: ST7694 (K. pneumoniae) and ST7699 (K. variicola). Survival and persistence analyses in Galleria mellonella showed that these isolates exhibited a virulent phenotype and an enhanced capacity for multiplication in the early hours of infection. CONCLUSION Clinically healthy swine act as reservoirs for multidrug-resistant Klebsiella spp. exhibiting significant virulence phenotypes. The identification of novel sequence types contributes to epidemiological surveillance and the One Health framework.
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Affiliation(s)
- Jéssica Nogueira Rosa
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Giarlã Cunha da Silva
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Patrícia Pereira Fontes
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Matheus Machado Guidini
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Rúzivia Pimentel Oliveira
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
| | - Denise Mara Soares Bazzolli
- Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
- Laboratório de Genética Molecular de Bactérias, Instituto de Biotecnologia Aplicada à Agropecuária-Bioagro, Universidade Federal de Viçosa, 36570-900, Viçosa, Minas Gerais, Brazil
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15
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Zhang M, Liu L, Yang X, Kang Y, Qin Q, Fu Y, Zhu L, Xu Y. Virulence phenotype alteration impacts nosocomial pathogen persistence on inanimate surfaces in hospital settings. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 958:177877. [PMID: 39667160 DOI: 10.1016/j.scitotenv.2024.177877] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/28/2024] [Accepted: 11/30/2024] [Indexed: 12/14/2024]
Abstract
The hospital setting serves as a critical conduit for pathogen dissemination, particularly amid the escalating concern of nosocomial infections in China. Currently, most studies use metagenomics to investigate microbial communities in hospital settings, with less focus on the transmission strategies of individual bacteria. In our study, we identified two Klebsiella pneumoniae strains exhibiting different mucoid characteristics. The strain designated as KPE was obtained from a well sanitized ward, while the strain KPH was isolated from the sputum samples of patients within the identical ward. We characterized the KPE strain as not lethal to mice and showed a distinct hypomuciod phenotype, strikingly different from the virulent KPH isolate. Two strains harbored the single nucleotide polymorphism (SNP) mutations in the virulence-related gene rmpA and wcaJ promoter regions, resulting in the downregulation of mucoid regulatory gene rmpA and capsule synthesis genes. Consequently, this led to diminished production of capsular polysaccharides and weakened virulence in the KPE strain. Furthermore, the KPE strain exhibited an elevated capacity for acquiring antibiotic-resistant plasmids and greater material survival ability. These findings indicated that mucoid changes enable K. pneumoniae strains to survive better on inanimate surfaces, promoting their persistence ward environment and further transmission in patients.
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Affiliation(s)
- Meng Zhang
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Lizhang Liu
- Department of Pharmacy, Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Xiaoqiang Yang
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Yanhua Kang
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Qiuying Qin
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Yingying Fu
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Lin Zhu
- School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Yongchang Xu
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China.
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Wu W, Ni S, Zheng Y, Zhang P, Jiang Y, Li X, Yu Y, Qu T. Hypervirulent carbapenem-susceptible klebsiella pneumoniae ST412/K57 with strong biofilm formation: association with gas gangrene and sepsis. Int J Antimicrob Agents 2024; 64:107373. [PMID: 39486468 DOI: 10.1016/j.ijantimicag.2024.107373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 10/09/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024]
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) poses a serious public health threat. Gas gangrene caused by hvKp is rarely reported and potentially results in a poor prognosis. This study describes the case of a hospitalised patient with gas gangrene and sepsis caused by hvKP. Carbapenem-susceptible hypervirulent Klebsiella pneumoniae (CS-hvKp) strains KPLSN and KPLSX were isolated from the knee joint pus and blood specimens of the patient for further investigations. Whole genome sequencing revealed that KPLSN and KPLSX were highly homologous (single nucleotide polymorphisms [SNPs]<10) and belonged to ST412/K57. The minimum inhibitory concentration and minimum bactericidal concentration under biofilm values of meropenem in KPLSN and KPLSX were significantly higher than in the planktonic state (>128 mg/L vs. 0.25 mg/L, P<0.0001). These two strains had high biofilm formation ability, and the results from fluorescence staining experiments showed that they were not easily killed by meropenem in the biofilm state. KPLSN and KPLSX showed high capsule production and were confirmed to have high virulence through experiments with the Galleria mellonella infection model and the BALB/c mice abdominal infection model. The persistent symptoms may be due to enhanced biofilm and capsule formation. Phylogenetic analysis of global ST412 strains showed their evolution towards higher virulence and resistance. These results emphasise the critical need for judicious antibiotic use and novel therapeutic approaches to combat special infections caused by these pathogens.
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Affiliation(s)
- Wenhao Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuangling Ni
- Department of Infectious Disease, Lishui City People's Hospital, Lishui, Zhejiang Province, China
| | - Yi Zheng
- Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Piaopiao Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Jiang
- Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xi Li
- Center of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
| | - Yunsong Yu
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
| | - Tingting Qu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.
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17
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Wei Y, Shi D, Chen T, Zhou S, Yang Z, Li H, Yang D, Li J, Jin M. Hypervirulent Klebsiella pneumoniae with a hypermucoviscosity phenotype challenges strategies of water disinfection for its capsular polysaccharides. WATER RESEARCH 2024; 266:122416. [PMID: 39265212 DOI: 10.1016/j.watres.2024.122416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/28/2024] [Accepted: 09/07/2024] [Indexed: 09/14/2024]
Abstract
Due to the strong pathogenicity of hypervirulent Klebsiella pneumoniae (hvKP), its performance against disinfectants in water should be understood to protect public health and ecological environment. Unfortunately, the disinfectant tolerance of hvKP with a hypermucoviscosity (HMV) phenotype is a critical underexplored area. Here, the tolerance of K. pneumoniae isolates to common disinfectants was evaluated, and its underlying mechanisms were clarified. Results showed that hvKP strains with HMV exhibited remarkable tolerance to triclosan (TCS), sodium hypochlorite (NaClO), and benzalkonium bromide (BB), surpassing that of low-virulent K. pneumoniae (lvKP) and Escherichia coli, which is the microbial indicator of drinking water quality. Ct value of NaClO reached 4.41 mg/L·min to kill 4-log hvKP, while the values were 2.52 and 2.28 mg/L·min to achieve 4-log killing of lvKP and E. coli, respectively. The curing of the virulence plasmid from hvKP strain K2044 revealed that capsular polysaccharide (CPS) synthesis, driven by the virulence plasmids, helped mitigate cell membrane injury and bacterial inactivation under NaClO stress; consequently, it provided a protective advantage to hvKP. Enhancing the antioxidative stress system to reduce ROS production and mitigate oxidative stress caused by NaClO further improved the disinfectant resistance of hvKP strains with HMV. This study emphasized that hvKP strains with HMV posed a considerable challenge to disinfection procedure of water treatment. It also revealed that an improved dosage of NaClO ensures bacteria killing, indicating the optimization of the design of water treatment processes involving disinfection strategies and technical parameters should be considered.
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Affiliation(s)
- Yijun Wei
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Danyang Shi
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Tianjiao Chen
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Shuqing Zhou
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Zhongwei Yang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Haibei Li
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Dong Yang
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Junwen Li
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China
| | - Min Jin
- State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, No1 Dali Road, Tianjin 300050, China.
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Miller JC, Cross AS, Tennant SM, Baliban SM. Klebsiella pneumoniae Lipopolysaccharide as a Vaccine Target and the Role of Antibodies in Protection from Disease. Vaccines (Basel) 2024; 12:1177. [PMID: 39460343 PMCID: PMC11512408 DOI: 10.3390/vaccines12101177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/26/2024] [Indexed: 10/28/2024] Open
Abstract
Klebsiella pneumoniae is well recognized as a serious cause of infection in healthcare-associated settings and immunocompromised individuals; however, accumulating evidence from resource-limited nations documents an alarming rise in community-acquired K. pneumoniae infections, manifesting as bacteremia and pneumonia as well as neonatal sepsis. The emergence of hypervirulent and antibiotic-resistant K. pneumoniae strains threatens treatment options for clinicians. Effective vaccination strategies could represent a viable alternative that would both preempt the need for antibiotics to treat K. pneumoniae infections and reduce the burden of K. pneumoniae disease globally. There are currently no approved K. pneumoniae vaccines. We review the evidence for K. pneumoniae lipopolysaccharide (LPS) as a vaccine and immunotherapeutic target and discuss the role of antibodies specific for the core or O-antigen determinants within LPS in protection against Klebsiella spp. disease. We expand on the known role of the Klebsiella spp. capsule and O-antigen modifications in antibody surface accessibility to LPS as well as the in vitro and in vivo effector functions reported for LPS-specific antibodies. We summarize key hypotheses stemming from these studies, review the role of humoral immunity against K. pneumoniae O-antigen for protection, and identify areas requiring further research.
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Affiliation(s)
- Jernelle C. Miller
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (J.C.M.); (A.S.C.); (S.M.T.)
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Alan S. Cross
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (J.C.M.); (A.S.C.); (S.M.T.)
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Sharon M. Tennant
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (J.C.M.); (A.S.C.); (S.M.T.)
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Scott M. Baliban
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (J.C.M.); (A.S.C.); (S.M.T.)
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
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19
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Wang Y. Case Study and Genomic Analysis of a Hypervirulent ST25 Klebsiella pneumoniae Strain in a Liver Cirrhosis Patient. Infect Drug Resist 2024; 17:4205-4212. [PMID: 39355781 PMCID: PMC11444233 DOI: 10.2147/idr.s487700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 09/21/2024] [Indexed: 10/03/2024] Open
Abstract
Bloodstream infections (BSIs) caused by Klebsiella pneumoniae (K. pneumoniae) are associated with high morbidity and mortality rates. This study presents a sequence type 25 (ST25) strain of hypermucoid K. pneumoniae A1 isolated from the blood of a patient with liver cirrhosis (LC) who succumbed to severe infections. We performed whole-genome sequencing of K. pneumoniae A1, which revealed virulence factors and antibiotic resistance genes. The strain harbors virulence genes encoding aerobactin, salmochelin, yersiniabactin, enterobactin, and rmpA. Additionally, the strain possessed five drug resistance genes: blaSHV-110, blaSHV-81, fosA6, OqxA, and OqxB. We further constructed a phylogenetic tree using 98 ST25 K. pneumoniae strains downloaded from NCBI together with K. pneumoniae A1. Phylogenetic analysis revealed that our isolated strain was closely related to a highly virulent strain isolated from a neonate in our region, differing by only 123 single nucleotide polymorphisms (SNPs). K. pneumoniae A1 is highly suspected to be Hypervirulent Klebsiella pneumoniae (hvKp). This study provided the first in-depth genomic analysis of ST25 K. pneumoniae in a patient with LC in China, highlighting the urgent need for early identification and diagnosis to combat this emerging threat.
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Affiliation(s)
- Yizhang Wang
- Department of Clinical Laboratory, Sanmen People’s Hospital, Sanmen, Zhejiang, People’s Republic of China
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20
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Watanabe N, Masuda A, Watari T, Otsuka Y, Yamagata K, Fujioka M. Evaluation of an optimal agar medium for detecting hypervirulent Klebsiella pneumoniae using string test. Access Microbiol 2024; 6:000834.v3. [PMID: 39697364 PMCID: PMC11652848 DOI: 10.1099/acmi.0.000834.v3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/21/2024] [Indexed: 12/20/2024] Open
Abstract
The string test is a screening method for detecting hypervirulent Klebsiella pneumoniae (hvKp). Agar media are used for string tests; however, the effect of the type of media on the test results remains unclear. We aimed to determine the optimal agar medium and cutoff value for the string test. We performed the string test on 99 Klebsiella strains using different agar media: sheep blood, chocolate, Drigalski's and MacConkey. The diagnostic accuracy was calculated in concordance with the rmpA, rmpA2 or iucA gene levels. The diagnostic accuracy rates for sheep blood, chocolate, Drigalski's and MacConkey agar were 0.79, 0.75, 0.73 and 0.64, respectively. When the cutoff was changed from 5 to 10 mm, the diagnostic accuracy rate for sheep blood agar decreased from 0.79 to 0.65. Our findings suggest that the type of agar medium impacts the string test results and sheep blood agar with a 5-mm cutoff is the optimal condition for detecting hvKp.
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Affiliation(s)
- Naoki Watanabe
- Clinical Laboratory, Kameda Medical Center, Higashi-cho 929, Kamogawa, Chiba 296-8602, Japan
- Graduate School of Health Sciences, Hirosaki University, Hon-cho 66-1, Hirosaki, Aomori, 036-8564, Japan
| | - Akari Masuda
- Clinical Laboratory, Kameda Medical Center, Higashi-cho 929, Kamogawa, Chiba 296-8602, Japan
| | - Tomohisa Watari
- Clinical Laboratory, Kameda Medical Center, Higashi-cho 929, Kamogawa, Chiba 296-8602, Japan
| | - Yoshihito Otsuka
- Clinical Laboratory, Kameda Medical Center, Higashi-cho 929, Kamogawa, Chiba 296-8602, Japan
| | - Kazufumi Yamagata
- Graduate School of Health Sciences, Hirosaki University, Hon-cho 66-1, Hirosaki, Aomori, 036-8564, Japan
| | - Miyuki Fujioka
- Graduate School of Health Sciences, Hirosaki University, Hon-cho 66-1, Hirosaki, Aomori, 036-8564, Japan
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21
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Yamamoto K, Hasegawa I, Suga Y, Kano Y. A Case of Pylephlebitis Without Intra-abdominal Infection Secondary to Pneumonia Caused by Hypermucoviscous Klebsiella pneumoniae. Cureus 2024; 16:e69428. [PMID: 39411641 PMCID: PMC11474013 DOI: 10.7759/cureus.69428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2024] [Indexed: 10/19/2024] Open
Abstract
Pylephlebitis is an infective, suppurative thrombosis of the portal vein that is often a complication of intra-abdominal infections. Herein, we report a rare case of hypermucoviscous Klebsiella pneumoniae pneumonia complicated by pylephlebitis. The patient was administered antibiotics and anticoagulants. His pneumonia improved; however, the thrombus in the portal vein did not shrink, and the patient ultimately died of liver failure. Furthermore, hypermucoviscous K. pneumoniae is involved in the formation of portal vein thrombosis, and if bacteremia persists even after pneumonia has improved, investigating possible complications, including portal vein inflammation, is necessary.
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Affiliation(s)
- Kohei Yamamoto
- Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, JPN
| | - Isao Hasegawa
- Respiratory Medicine, Saiseikai Shiga Hospital, Moriyama, JPN
| | - Yoshifumi Suga
- Respiratory Medicine, Saiseikai Shiga Hospital, Moriyama, JPN
| | - Yukari Kano
- Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, JPN
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22
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Jauvain M, Carrer M, Palma F, Chapuzet C, Courat N, Heslan C, Pereyre S, Cazanave C, Brisse S. Bacteraemia associated with multiple septic localizations caused by Klebsiella pneumoniae sequence type ST660. Eur J Clin Microbiol Infect Dis 2024; 43:1655-1659. [PMID: 38869685 DOI: 10.1007/s10096-024-04870-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/29/2024] [Indexed: 06/14/2024]
Abstract
We report a case of Klebsiella pneumoniae bacteraemia in an 80-year-old man in France with no history of travel to Asia, complicated by endogenous endophthalmitis, multiple cerebral microbleeds and hepatic microabscesses, associated with a Bentall endocarditis. Hypervirulence pathotype was suggested based on clinical picture, bacterial isolate genomic sequence and hypermucoidy. Interestingly, the isolate had the non-K1/K2-capsular serotype locus KL113-like, carried a KpVP-1-like virulence plasmid, and belonged to the emerging sublineage SL660 (comprising the sequence type ST660).
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Affiliation(s)
- Marine Jauvain
- Bacteriology department, CHU Bordeaux, Bordeaux, F-33000, France.
- Bordeaux Institute of Oncology, BRIC U1312, INSERM, University of Bordeaux, Bordeaux, F-33000, France.
| | - Mathilde Carrer
- Infectious diseases department, CHU Bordeaux, Bordeaux, F-33000, France
| | - Federica Palma
- Institut Pasteur, Université Paris Cité, Biological Resource Center of the Institut Pasteur, Paris, F-75015, France
| | - Claire Chapuzet
- Infectious diseases department, Hôpital Saint Louis de La Rochelle, La Rochelle, F-17000, France
| | - Nathan Courat
- Ophthalmology department, Hôpital Saint Louis de La Rochelle, La Rochelle, F-17000, France
| | - Christopher Heslan
- Biology department, Hôpital Saint Louis de La Rochelle, La Rochelle, F-17000, France
| | - Sabine Pereyre
- Bacteriology department, CHU Bordeaux, Bordeaux, F-33000, France
- UMR 5234, CNRS, University of Bordeaux, Bordeaux, F-33000, France
| | - Charles Cazanave
- Infectious diseases department, CHU Bordeaux, Bordeaux, F-33000, France
| | - Sylvain Brisse
- Institut Pasteur, Université Paris Cité, Biological Resource Center of the Institut Pasteur, Paris, F-75015, France
- Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, F-75015, France
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23
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Hamada H, Hayashi K, Morikawa Y, Hayashi M, Shirasaki A, Yamamoto C. Iliopsoas Abscess, Spondylodiscitis, Septic Pulmonary Embolism, and Symmetrical Peripheral Gangrene by Hypermucoviscous Klebsiella pneumoniae. Cureus 2024; 16:e67985. [PMID: 39347316 PMCID: PMC11427936 DOI: 10.7759/cureus.67985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2024] [Indexed: 10/01/2024] Open
Abstract
Hypermucoviscous Klebsiella pneumoniae (hmKP) is a bacterium known to cause lesions, including abscesses, in various organs. Unlike typical Klebsiella pneumoniae, hmKP can yield a positive string test in culture specimens. Infections caused by hmKP often become severe and are associated with a poor prognosis. In this report, we describe a case of iliopsoas abscess, spondylodiscitis, septic pulmonary embolism, and symmetrical peripheral gangrene (SPG) caused by hmKP. The patient received non-invasive positive-pressure ventilation, hemodialysis, platelet transfusions, fresh frozen plasma, thrombomodulin, and intensive antibiotic therapy including rifampicin. The patient underwent 148 days of antibiotic therapy and achieved a good outcome.
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Affiliation(s)
- Hina Hamada
- Department of Internal Medicine, Fukui General Hospital, Fukui, JPN
| | - Koji Hayashi
- Department of Rehabilitation Medicine, Fukui General Hospital, Fukui, JPN
| | - Yukie Morikawa
- Department of Internal Medicine, Fukui General Hospital, Fukui, JPN
| | - Maho Hayashi
- Department of Internal Medicine, Fukui General Hospital, Fukui, JPN
| | | | - Chie Yamamoto
- Department of Internal Medicine, Fukui General Hospital, Fukui, JPN
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24
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Ando Y, Matsukawa H, Suto H, Oshima M, Sanomura T, Kamada H, Kumamoto K, Yokota K, Suzuki Y, Okano K. A rare case of hypervirulent Klebsiella pneumoniae liver abscess and bacterial endophthalmitis associated with distal bile duct cancer. Clin J Gastroenterol 2024; 17:731-736. [PMID: 38888806 DOI: 10.1007/s12328-024-01985-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 05/06/2024] [Indexed: 06/20/2024]
Abstract
We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings.
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Affiliation(s)
- Yasuhisa Ando
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan.
| | - Hiroyuki Matsukawa
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Hironobu Suto
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Minoru Oshima
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Takayuki Sanomura
- Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Hideki Kamada
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Kensuke Kumamoto
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Kyoko Yokota
- Department of Infectious Diseases, Kagawa Prefectural Central Hospital, Asahi-Machi 1-2-1, Takamatsu-Shi, Kagawa, 760-8557, Japan
| | - Yasuyuki Suzuki
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
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25
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Muner JJ, de Oliveira PAA, Baboghlian J, Moura SC, de Andrade AG, de Oliveira MM, Campos YFD, Mançano ASF, Siqueira NMG, Pacheco T, Ferraz LFC. The transcriptional regulator Fur modulates the expression of uge, a gene essential for the core lipopolysaccharide biosynthesis in Klebsiella pneumoniae. BMC Microbiol 2024; 24:279. [PMID: 39061004 PMCID: PMC11282780 DOI: 10.1186/s12866-024-03418-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Klebsiella pneumoniae is a Gram-negative pathogen that has become a threat to public health worldwide due to the emergence of hypervirulent and multidrug-resistant strains. Cell-surface components, such as polysaccharide capsules, fimbriae, and lipopolysaccharides (LPS), are among the major virulence factors for K. pneumoniae. One of the genes involved in LPS biosynthesis is the uge gene, which encodes the uridine diphosphate galacturonate 4-epimerase enzyme. Although essential for the LPS formation in K. pneumoniae, little is known about the mechanisms that regulate the expression of uge. Ferric uptake regulator (Fur) is an iron-responsive transcription factor that modulates the expression of capsular and fimbrial genes, but its role in LPS expression has not yet been identified. This work aimed to investigate the role of the Fur regulator in the expression of the K. pneumoniae uge gene and to determine whether the production of LPS by K. pneumoniae is modulated by the iron levels available to the bacterium. RESULTS Using bioinformatic analyses, a Fur-binding site was identified on the promoter region of the uge gene; this binding site was validated experimentally through Fur Titration Assay (FURTA) and DNA Electrophoretic Mobility Shift Assay (EMSA) techniques. RT-qPCR analyses were used to evaluate the expression of uge according to the iron levels available to the bacterium. The iron-rich condition led to a down-regulation of uge, while the iron-restricted condition resulted in up-regulation. In addition, LPS was extracted and quantified on K. pneumoniae cells subjected to iron-replete and iron-limited conditions. The iron-limited condition increased the amount of LPS produced by K. pneumoniae. Finally, the expression levels of uge and the amount of the LPS were evaluated on a K. pneumoniae strain mutant for the fur gene. Compared to the wild-type, the strain with the fur gene knocked out presented a lower LPS amount and an unchanged expression of uge, regardless of the iron levels. CONCLUSIONS Here, we show that iron deprivation led the K. pneumoniae cells to produce higher amount of LPS and that the Fur regulator modulates the expression of uge, a gene essential for LPS biosynthesis. Thus, our results indicate that iron availability modulates the LPS biosynthesis in K. pneumoniae through a Fur-dependent mechanism.
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Affiliation(s)
- José Júlio Muner
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
| | - Paloma Aparecida Alves de Oliveira
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
- Central Multiusuária de Análises Genômica e Transcriptômica (CmAGT), Universidade São Francisco, Bragança Paulista, SP, Brazil
| | - Juliana Baboghlian
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
| | - Stefany Casarin Moura
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
| | | | | | - Yasmin Ferreira de Campos
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
| | | | | | - Thaisy Pacheco
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil
| | - Lúcio Fábio Caldas Ferraz
- Laboratório de Microbiologia Molecular e Clínica, Universidade São Francisco, Bragança Paulista, SP, Brazil.
- Central Multiusuária de Análises Genômica e Transcriptômica (CmAGT), Universidade São Francisco, Bragança Paulista, SP, Brazil.
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26
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Müller JU, Schwabe M, Swiatek LS, Heiden SE, Schlüter R, Sittner M, Bohnert JA, Becker K, Idelevich EA, Guenther S, Eger E, Schaufler K. Temperatures above 37°C increase virulence of a convergent Klebsiella pneumoniae sequence type 307 strain. Front Cell Infect Microbiol 2024; 14:1411286. [PMID: 38947124 PMCID: PMC11211929 DOI: 10.3389/fcimb.2024.1411286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/23/2024] [Indexed: 07/02/2024] Open
Abstract
Background Convergence of Klebsiella pneumoniae (KP) pathotypes has been increasingly reported in recent years. These pathogens combine features of both multidrug-resistant and hypervirulent KP. However, clinically used indicators for hypervirulent KP identification, such as hypermucoviscosity, appear to be differentially expressed in convergent KP, potential outbreak clones are difficult to identify. We aimed to fill such knowledge gaps by investigating the temperature dependence of hypermucoviscosity and virulence in a convergent KP strain isolated during a clonal outbreak and belonging to the high-risk sequence type (ST)307. Methods Hypermucoviscosity, biofilm formation, and mortality rates in Galleria mellonella larvae were examined at different temperatures (room temperature, 28°C, 37°C, 40°C and 42°C) and with various phenotypic experiments including electron microscopy. The underlying mechanisms of the phenotypic changes were explored via qPCR analysis to evaluate plasmid copy numbers, and transcriptomics. Results Our results show a temperature-dependent switch above 37°C towards a hypermucoviscous phenotype, consistent with increased biofilm formation and in vivo mortality, possibly reflecting a bacterial response to fever-like conditions. Furthermore, we observed an increase in plasmid copy number for a hybrid plasmid harboring carbapenemase and rmpA genes. However, transcriptomic analysis revealed no changes in rmpA expression at higher temperatures, suggesting alternative regulatory pathways. Conclusion This study not only elucidates the impact of elevated temperatures on hypermucoviscosity and virulence in convergent KP but also sheds light on previously unrecognized aspects of its adaptive behavior, underscoring its resilience to changing environments.
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Affiliation(s)
- Justus U. Müller
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Michael Schwabe
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Lena-Sophie Swiatek
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Stefan E. Heiden
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Rabea Schlüter
- Imaging Center of the Department of Biology, University of Greifswald, Greifswald, Germany
| | - Max Sittner
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Jürgen A. Bohnert
- Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany
| | - Karsten Becker
- Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany
| | - Evgeny A. Idelevich
- Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany
- Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
| | - Sebastian Guenther
- Pharmaceutical Biology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany
| | - Elias Eger
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
| | - Katharina Schaufler
- Department of Epidemiology and Ecology of Antimicrobial Resistance, Helmholtz Institute for One Health, Helmholtz Centre for Infection Research (HZI), Greifswald, Germany
- University Medicine Greifswald, Greifswald, Germany
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27
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Liao Y, Gong J, Yuan X, Wang X, Huang Y, Chen X. Virulence Factors and Carbapenem-Resistance Mechanisms in Hypervirulent Klebsiella Pneumoniae. Infect Drug Resist 2024; 17:1551-1559. [PMID: 38660055 PMCID: PMC11042477 DOI: 10.2147/idr.s461903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 04/11/2024] [Indexed: 04/26/2024] Open
Abstract
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.
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Affiliation(s)
- Yiqun Liao
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China
| | - Junjie Gong
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China
| | - Xiaoliang Yuan
- Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China
| | - Xiaoling Wang
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China
| | - Yuanhong Huang
- Department of Laboratory Medicine, Ganzhou Municipal Hospital, Ganzhou, People’s Republic of China
| | - Xiaohong Chen
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China
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Kain MJW, Reece NL, Parry CM, Rajahram GS, Paterson DL, Woolley SD. The Rapid Emergence of Hypervirulent Klebsiella Species and Burkholderia pseudomallei as Major Health Threats in Southeast Asia: The Urgent Need for Recognition as Neglected Tropical Diseases. Trop Med Infect Dis 2024; 9:80. [PMID: 38668541 PMCID: PMC11054678 DOI: 10.3390/tropicalmed9040080] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 03/29/2024] [Accepted: 04/05/2024] [Indexed: 04/29/2024] Open
Abstract
The World Health Organization (WHO)'s list of neglected tropical diseases (NTDs) highlights conditions that are responsible for devastating health, social and economic consequences, and yet, they are overlooked and poorly resourced. The NTD list does not include conditions caused by Gram-negative bacilli (GNB). Infections due to GNB cause significant morbidity and mortality and are prevalent worldwide. Southeast Asia is a WHO region of low- and middle-income countries carrying the largest burden of NTDs. Two significant health threats in Southeast Asia are Burkholderia pseudomallei (causing melioidosis) and hypervirulent Klebsiella pneumoniae (HvKp). Both diseases have high mortality and increasing prevalence, yet both suffer from a lack of awareness, significant under-resourcing, incomplete epidemiological data, limited diagnostics, and a lack of evidence-based treatment. Emerging evidence shows that both melioidosis and HvKp are spreading globally, including in high-income countries, highlighting the potential future global threat they pose. In this article, we review both conditions, identifying current trends and challenges in Southeast Asia and areas for future research. We also argue that melioidosis and HvKp merit inclusion as NTDs, and that mandatory global surveillance and reporting systems should be established, and we make an urgent call for research to better understand, detect, and treat these neglected diseases.
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Affiliation(s)
| | | | - Christopher M. Parry
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK;
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 2JD, UK
| | - Giri Shan Rajahram
- Department of Medicine, Queen Elizabeth II Hospital, Kota Kinabalu 88300, Malaysia
- Infectious Diseases Society, Kota Kinabalu Sabah-Menzies School of Health Research, Clinical Research Unit, Kota Kinabalu 88994, Malaysia
| | - David L. Paterson
- ADVANCE-ID Network, Saw Swee Hock School of Public Health, National University of Singapore, Singapore 119077, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Stephen D. Woolley
- Institute of Naval Medicine, Alverstoke, Hampshire PO12 2DL, UK
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK;
- Tropical and Infectious Diseases Unit, Liverpool University Hospitals Foundation NHS Trust, Liverpool L7 8YE, UK
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Yomogida D, Kuwano H, Miyakoshi T, Mizuta S, Horikawa S, Koshida Y. Prognosis and Characteristics of Hypermucoviscous Klebsiella pneumoniae Infection in Critically Ill Patients: A Case Series. Cureus 2024; 16:e59094. [PMID: 38800315 PMCID: PMC11128319 DOI: 10.7759/cureus.59094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction Hypermucoviscous Klebsiella pneumoniae (hvKP) is related to invasive infections; however, there have been very few comprehensive reports on the clinical features and prognosis of critically ill patients with the infection. Methods We conducted a retrospective case series in a general intensive care unit in Japan. Patients with positive blood cultures for KP between January 1, 2020 and December 31, 2022 were included. hvKP was defined by the positivity in the string test. We analyzed the patient's characteristics at baseline, including comorbidities, abscess formation, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, septic shock, duration of hospitalization, 30-day mortality, and infection site. Results A total of 24 patients had a positive blood culture for KP; nine patients (37.5%) were positive for the string test (hvKP) while 15 (62.5%) were negative (non-hvKP). In both groups, the patients were old (mean age, hvKP 80.4 vs. non-hvKP 75.7 years) and more often male (five patients (55.6%) vs. 12 patients (80.0%)). No statistically significant difference was found between the two groups in terms of comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy. No statistical difference was seen in abscess formation (two patients [22.2%] vs. one patient (6.7%)), SOFA score (5.2±4.8 vs. 4.7±3.4), APACHE II score (19.6 (15.0-20.0) vs. 17.0 (11.2-20.8)), septic shock (five patients (55.6%) vs. four patient (26.7%)), duration of hospitalization (37.2 (12.0-51.0) vs. 32.3 (9.5-21.0)), and 30-day mortality (two patients (22.2%) vs. two patients (13.3%)). Two cases with hvKP died within 24 h. No significant difference was seen in the infection sources; respiratory infection (2 (22.2%) vs. 1 (6.7%)), hepatobiliary infection (2 (22.2%) vs. 7 (46.7%)), and genitourinary infection (1 (11.1%) vs. 5 (33.3%)). Conclusions Critically ill patients with hvKP infection showed characteristics similar to those reported previously. However, the disease could rapidly become severe and have a poor prognostic outcome.
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Affiliation(s)
- Daichi Yomogida
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
| | - Hiroyuki Kuwano
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
| | - Tatsuya Miyakoshi
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
| | - Shiori Mizuta
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
| | - Shinjiro Horikawa
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
| | - Yosinao Koshida
- Intensive Care Medicine, Toyama Prefectural Central Hospital, Toyama, JPN
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30
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Abbas R, Chakkour M, Zein El Dine H, Obaseki EF, Obeid ST, Jezzini A, Ghssein G, Ezzeddine Z. General Overview of Klebsiella pneumonia: Epidemiology and the Role of Siderophores in Its Pathogenicity. BIOLOGY 2024; 13:78. [PMID: 38392297 PMCID: PMC10886558 DOI: 10.3390/biology13020078] [Citation(s) in RCA: 35] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/23/2024] [Accepted: 01/24/2024] [Indexed: 02/24/2024]
Abstract
The opportunistic pathogen Klebsiella pneumoniae (K. pneumoniae) can colonize mucosal surfaces and spread from mucosae to other tissues, causing fatal infections. Medical equipment and the healthcare setting can become colonized by Klebsiella species, which are widely distributed in nature and can be found in water, soil, and animals. Moreover, a substantial number of community-acquired illnesses are also caused by this organism worldwide. These infections are characterized by a high rate of morbidity and mortality as well as the capacity to spread metastatically. Hypervirulent Klebsiella strains are thought to be connected to these infections. Four components are critical to this bacterium's pathogenicity-the capsule, lipopolysaccharide, fimbriae, and siderophores. Siderophores are secondary metabolites that allow iron to sequester from the surrounding medium and transport it to the intracellular compartment of the bacteria. A number of variables may lead to K. pneumoniae colonization in a specific area. Risk factors for infection include local healthcare practices, antibiotic use and misuse, infection control procedures, nutrition, gender, and age.
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Affiliation(s)
- Rim Abbas
- Faculty of Health Sciences, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon
| | - Mohamed Chakkour
- Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA
| | - Hiba Zein El Dine
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
| | | | - Soumaya T Obeid
- Laboratory Sciences Department, Faculty of Public Health, Islamic University of Lebanon (IUL), Khalde P.O. Box 30014, Lebanon
| | - Aya Jezzini
- Laboratory Sciences Department, Faculty of Public Health, Islamic University of Lebanon (IUL), Khalde P.O. Box 30014, Lebanon
| | - Ghassan Ghssein
- Laboratory Sciences Department, Faculty of Public Health, Islamic University of Lebanon (IUL), Khalde P.O. Box 30014, Lebanon
| | - Zeinab Ezzeddine
- Laboratory Sciences Department, Faculty of Public Health, Islamic University of Lebanon (IUL), Khalde P.O. Box 30014, Lebanon
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Lim SY, Kwon HJ, Lee YW, Sung H, Kim MN, Chang E, Bae S, Jung J, Kim MJ, Kim SH, Choi SH, Lee SO, Kim YS, Lee JY, Chong YP. Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement. Antimicrob Agents Chemother 2023; 67:e0082223. [PMID: 37874294 PMCID: PMC10648850 DOI: 10.1128/aac.00822-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/12/2023] [Indexed: 10/25/2023] Open
Abstract
Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.
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Affiliation(s)
- So Yun Lim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hye Ji Kwon
- Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yun Woo Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Mi-Na Kim
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Euijin Chang
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seongman Bae
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Joo Yong Lee
- Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Alvarado-Delgado A, Rodríguez-Medina N, Sánchez-Pérez A, Tamayo-Legorreta EM, Cerón-Lopez J, Morfin-Otero R, Garza-Ramos U. Genome sequence of a virulent and hypermucoviscous-like Klebsiella michiganensis clinical isolate. BMC Res Notes 2023; 16:334. [PMID: 37964369 PMCID: PMC10647098 DOI: 10.1186/s13104-023-06603-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 10/27/2023] [Indexed: 11/16/2023] Open
Abstract
OBJECTIVES The hypermucoviscous-like phenotype has been described in Klebsiella pneumoniae species complex (KpSC) and was described as a contributor of increased virulence. This study described the characterization and whole-genome sequencing of an antibiotic susceptible and hypermucoviscous-like Klebsiella michiganensis 9273 clinical isolate. DATA DESCRIPTION Here, we report the genome sequence of a K. michiganensis clinical isolate obtained from a urinary tract infection exhibiting the hypermucoviscous-like phenotype. The draft genome sequence consisted of 145 contigs and ~ 6.6 Mb genome size. The annotation revealed 6648 coding DNA sequences and 56 tRNA genes. The strain belongs to the sequence type (ST) 50, and the OXY-1 beta-lactam resistance gene, aph(3')-Ia gene for aminoglycoside resistance and multidrug efflux pumps were identified. The fyuA siderophore receptor of yersiniabactin siderophore was identified. Increased virulence was observed in Galleria mellonella larvae model and increased capsule production was determined by uronic acid quantification. The clinical implications of this phenotype are unknown, but the patient outcome might worsen compared to susceptible- or MDR-classical K. michiganensis isolates.
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Affiliation(s)
- Alejandro Alvarado-Delgado
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México
| | - Nadia Rodríguez-Medina
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México
| | - Alejandro Sánchez-Pérez
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México
| | - Elsa María Tamayo-Legorreta
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México
| | - Jackeline Cerón-Lopez
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México
| | - Rayo Morfin-Otero
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - Ulises Garza-Ramos
- Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Grupo de Investigación y Docencia en Resistencia Antimicrobiana (GID-RAM), Cuernavaca, Morelos, México.
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Tada K, Shibata R, Nakamura T, Kawaguchi Y, Nakano Y, Ishii H, Ura K, Yamada H, Maekawa S, Ito K, Masutani K. Severe disseminated infection by hypermucoviscous Klebsiella pneumoniae successfully treated by intensive therapy with continuous hemodiafiltration using AN69ST: A case report and review of the literature. J Infect Chemother 2023; 29:1075-1080. [PMID: 37451619 DOI: 10.1016/j.jiac.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/09/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Klebsiella pneumoniae (Kpn) is one of the most common gram-negative bacilli causing lung, urinary tract, and biliary tract infections. However, as a distinct entity from classic Kpn, hypervirulent Kpn causing liver abscess, endophthalmitis, and lung abscess with poor prognoses has been reported mainly in East and Southeast Asia since the mid-1980s. Although the definition of hypervirulent Kpn is unclear, the hypermucoviscosity of Kpn is considered an important feature of hypervirulence. We present a case of emphysematous pyelonephritis accompanied by septic shock and acute kidney injury caused by hypermucoviscous Kpn infection that was successfully treated by intensive treatment. A 70-year-old woman with type 2 diabetes mellitus was diagnosed with emphysematous pyelonephritis, and string test-positive Kpn was detected in blood and urine cultures and percutaneous catheter drainage fluid from the renal pelvis. The patient was treated with intensive therapies including antibiotics, ventilator management, and continuous hemodiafiltration (CHDF) using AN69ST, which can absorb cytokines. During the course of treatment, the infection was complicated by pyogenic spondylitis, which was cured by antimicrobial therapy, and the patient was transferred to another hospital for rehabilitation on day 119 after admission. Hypermucoviscous Kpn infection often has a severe course, and it is important to initiate multidisciplinary treatment at an early stage, including rifampicin, which is expected to inhibit the viscosity of hypermucoviscous Kpn. In the current case, immediate CHDF using AN69ST was also considered a life-saving treatment because it improved both volume overload and neutrophil-activated hypercytokinemia.
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Affiliation(s)
- Kazuhiro Tada
- Department of Nephrology, Saiseikai Futsukaichi Hospital, Fukuoka, Japan.
| | - Ryoko Shibata
- Department of Nephrology, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Tsubasa Nakamura
- Department of Nephrology, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | | | - Yuki Nakano
- Department of Pharmacy, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Hidehiro Ishii
- Department of Diabetology, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Kazuya Ura
- Department of General Internal Medicine, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Hiroyoshi Yamada
- Department of Respiratory Medicine, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Shinichi Maekawa
- Department of General Thoracic Surgery, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Kenji Ito
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Kosuke Masutani
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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Elmogassabi A, Gul T, Tallai B, Alrayashi M, Abdelkareem M, Ibrahim M, Baker A, Ebrahim M, Alnawasra H, Alhabash S, Salah M. Successful management of emphysematous prostatic abscess and concurrent liver abscess: A rare case report. Urol Case Rep 2023; 51:102571. [PMID: 37818411 PMCID: PMC10561036 DOI: 10.1016/j.eucr.2023.102571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/14/2023] [Accepted: 09/20/2023] [Indexed: 10/12/2023] Open
Abstract
Emphysematous prostatic abscess (EPA) is a rare condition characterized by gas and abscess accumulation in the prostate. In this case report we report a successfully treated EPA with liver abscess due to Klebsiella pneumoniae in a 49-year-old man. He was admitted with abdominal pain and fever. Physical examination revealed tender, palpable resonance urinary bladder, and prostatic tenderness on rectal digital examination. High inflammatory markers were found. Abdominal computer tomography (CT) confirmed EPA. The patient was treated with broad-spectrum antibiotics, strict blood glucose control, suprapubic catheterization, and transurethral deroofing of the prostatic abscess. After three weeks patient discharged in good condition.
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Affiliation(s)
- Abdoulhafid Elmogassabi
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Tawiz Gul
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
- College of Medicine, Qatar University, Doha, Qatar
| | - Bela Tallai
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Maged Alrayashi
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Mohamed Abdelkareem
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Mohammed Ibrahim
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Abu Baker
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Mohammed Ebrahim
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Hossameldin Alnawasra
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Salvan Alhabash
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
| | - Morshed Salah
- Urology Section, Surgery Department, Hazm Mebaireek General Hospital, Hamad Medical Corporation, Qatar
- College of Medicine, Qatar University, Doha, Qatar
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Wang Y, Ouyang Y, Xu X, Sun S, Tian X, Liu H, Xia Y. Dissemination and characteristics of carbapenem-resistant Klebsiella pneumoniae in nine district hospitals in southwestern China. Front Microbiol 2023; 14:1269408. [PMID: 37942077 PMCID: PMC10628634 DOI: 10.3389/fmicb.2023.1269408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/10/2023] [Indexed: 11/10/2023] Open
Abstract
Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is epidemically transmitted globally, but few studies focused on the prevalence in district-level hospitals. In this study, we investigated CRKP strains collected from nine district hospitals from September 2019 to September 2020, aiming to determine the resistance mechanisms, virulence profiles, and molecular epidemiological characteristics of CRKP in district hospitals in Southwest China. Methods A total of 51 CRKP strains were collected from 9 district-level hospitals. Matrix-assisted laser desorption/ionization-time of flight mass spectrometer was used for strain identification review, and the micro-broth dilution method was used for antibiotic sensitivity detection. Molecular epidemiological investigation of strains was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) methods. PCR and efflux pump inhibition tests were used to detect CRKP resistance mechanisms. PCR and serum killing tests were used to detect capsular serotype, virulence-related genes, and virulence validation. Results The CRKP strains in district hospitals presented high levels of MIC50 and MIC90 in carbapenem antibiotics especially ertapenem and meropenem. A total of 90.2% (46/51) CRKP strains were detected as carbapenemase producers, and the proportion of strains co-expressing carbapenemases was 11.8% (6/51). All CRKP strains were grouped into eight MLST types, and ST11 was the most prevalent genotype. A total of 11.8% (6/51) CRKP isolates were positive for the string test, and three strains of hypervirulent and carbapenem-resistant K. pneumoniae (HV-CRKP) were positive in serum killing test. The molecular typing of all the CRKP isolates was grouped into 29 different PFGE patterns, and 40 ST11 isolates belonged to 20 different PFGE clusters. Conclusion CRKP strains showed high-level antibiotic resistance and virulence phenotype in district hospitals in Southwest China, which suggested that we should immediately pay attention to the rapid dissemination of the CRKP in regional hospitals. Our study will provide new insights into the epidemiology of CRKP in regional hospitals, which will help regional hospitals develop nosocomial infection prevention and control policies tailored to local conditions.
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Affiliation(s)
- Yonghong Wang
- Department of Clinical Laboratory, Chongqing Qianjiang Central Hospital, Chongqing University Qianjiang Hospital, Chongqing, China
- Qianjiang Key Laboratory of Chongqing Qianjiang Central Hospital Laboratory Medicine, Chongqing, China
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Ouyang
- Department of Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiuyu Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shan Sun
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaolang Tian
- Department of Clinical Laboratory, The Fifth People’s Hospital of Chongqing, Chongqing, China
| | - Hang Liu
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yun Xia
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Abstract
Pyogenic liver abscesses (PLAs) are a suppurative infection of the hepatic parenchyma responsible for significant morbidity and mortality. PLAs are categorized into a variety of mechanisms: (1) via the portal vein, (2) through the biliary tract, (3) via the hepatic artery, (4) from trauma, (5) contiguously via direct extension, and (6) cryptogenically. The pathogenesis of PLA, which informs treatment, can often be discerned based on host factors, clinical presentation, and causative microorganisms. The Streptococcus anginosus group, hypervirulent Klebsiella pneumoniae , and multidrug-resistant gram-negative pathogens have emerged as microbiologically challenging organisms to treat. The identification of hypervirulent K. pneumoniae should prompt for assessment for metastatic spread and consideration of prolonged antimicrobial treatment. Abdominal imaging is indispensable in characterizing PLAs and facilitating source control interventions. Source control remains the most critical aspect of PLA management, followed by antimicrobial therapy. Empiric antibiotics for PLAs are informed by the suspected etiology of PLA formation. Duration of antimicrobial therapy is individualized and dependent on multiple components, including the success of achieving source control, host factors, mechanism of PLA development, and the illness course of the individual-factoring in clinical, biochemical, and radiographic parameters.
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Affiliation(s)
- John C Lam
- Division of Infectious Diseases, Department of Medicine, University of California Los Angeles, Los Angeles, CA
| | - William Stokes
- Provincial Laboratory for Public Health, Alberta Precision Laboratories, Calgary
- Department of Pathology and Laboratory Medicine, University of Alberta
- Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, AB, Canada
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Wang L, Huang X, Jin Q, Tang J, Zhang H, Zhang JR, Wu H. Two-Component Response Regulator OmpR Regulates Mucoviscosity through Energy Metabolism in Klebsiella pneumoniae. Microbiol Spectr 2023; 11:e0054423. [PMID: 37097167 PMCID: PMC10269446 DOI: 10.1128/spectrum.00544-23] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/02/2023] [Indexed: 04/26/2023] Open
Abstract
Hypermucoviscosity is a hallmark of hypervirulent Klebsiella pneumoniae (hvKP). However, the molecular basis of its regulation is largely unknown. We hypothesize that hypermucoviscosity is modulated via two-component signal transduction systems (TCSs). In-frame deletion mutants of all 33 response regulators of hvKP ATCC43816 were generated using CRISPR/CAS and evaluated for their impacts on hypermucoviscosity. The response regulator OmpR is required for hypermucoviscosity in vitro and virulence in vivo in a mouse pneumonia model. The ΔompR mutant lost its mucoidy but retained its capsule level and comparable rmpADC expression, so transcriptomic analysis by RNA-Seq was performed to identify differentially expressed genes (DEGs) in ΔompR mutant. The top 20 Gene Ontology terms of 273 DEGs belong to purine ribonucleotide triphosphate biosynthetic and metabolic process, transmembrane transport, and amino acid metabolism. Among the overexpressed genes in the ΔompR mutant, the atp operon encoding F-type ATP synthase and the gcvTHP encoding glycine cleavage system were characterized further as overexpression of either operon reduced the mucoviscosity and increased the production of ATP. Furthermore, OmpR directly bound the promoter region of the atp operon, not the gcvTHP, suggesting that OmpR regulates the expression of the atp operon directly and gcvTHP indirectly. Hence, the loss of OmpR led to the overexpression of F-type ATP synthase and glycine cleavage system, which altered the energetic status of ΔompR cells and contributed to the subsequent reduction in the mucoviscosity. Our study has uncovered a previously unknown regulation of bacterial metabolism by OmpR and its influence on hypermucoviscosity. IMPORTANCE Hypermucoviscosity is a critical virulent factor for Klebsiella pneumoniae infections, and its regulation remains poorly understood at the molecular level. This study aims to address this knowledge gap by investigating the role of response regulators in mediating hypermucoviscosity in K. pneumoniae. We screened 33 response regulators and found that OmpR is essential for hypermucoviscosity and virulence of K. pneumoniae in a mouse pneumonia model. Transcriptomic analysis uncovered that genes involved in energy production and metabolism are highly upregulated in the ΔompR mutant, suggesting a potential link between bacterial energy status and hypermucoviscosity. Overexpression of those genes increased production of ATP and reduced mucoviscosity, recapitulating the ΔompR mutant phenotype. Our findings provide new insights into the regulation of K. pneumoniae hypermucoviscosity by a two-component signal transduction system, highlighting the previously unknown role of OmpR in regulating bacterial energy status and its influence on hypermucoviscosity.
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Affiliation(s)
- Lijun Wang
- Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Xueting Huang
- Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China
| | - Qian Jin
- Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China
| | - Jie Tang
- Department of Laboratory Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Hua Zhang
- Department of Integrative Biomedical and Diagnostic Sciences, Oregon Health and Science University School of Dentistry, Portland, Oregon, USA
| | - Jing-Ren Zhang
- Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China
- Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
| | - Hui Wu
- Department of Integrative Biomedical and Diagnostic Sciences, Oregon Health and Science University School of Dentistry, Portland, Oregon, USA
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Romo-Castillo M, Flores-Bautista VA, Guzmán-Gutiérrez SL, Reyes-Chilpa R, León-Santiago M, Luna-Pineda VM. Synergy of Plant Essential Oils in Antibiotic Therapy to Combat Klebsiella pneumoniae Infections. Pharmaceuticals (Basel) 2023; 16:839. [PMID: 37375786 DOI: 10.3390/ph16060839] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/25/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
Increased antibiotic resistance presents a health problem worldwide. The World Health Organization published a list of pathogens considered a priority for designing new treatments. Klebsiella pneumoniae (Kp) is a top-priority microorganism, highlighting the strains that produce carbapenemases. Developing new efficient therapies or complementing existing treatments is a priority, and essential oils (EOs) provide an alternative. EOs could act as antibiotic adjuvants and enhance antibiotic activity. Employing standard methodologies, the antibacterial activity of the EOs and their synergic effect with antibiotics were detected. A string test was used to identify the impact of the EOs over the hypermucoviscosity phenotype presented by Kp strains, and Gas Chromatography-Mass Spectrometry analysis identified EOs and the composition of EOs. The potential of EOs for designing synergistic therapies with antibiotics to combat the infection of KPC diseases was demonstrated. In addition, the alteration of the hypermucoviscosity phenotype was shown as the principal mechanism of a synergic action between EOs and antibiotics. The differential composition of the EOs lets us identify some molecules that will be analyzed. Synergic activity of EOs and antibiotics can provide a solid platform for combating multiresistant pathogens that represent a severe health sector problem, such as Kp infections.
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Affiliation(s)
- Mariana Romo-Castillo
- CONAHCYT/HIMFG, Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
| | - Victor Andrés Flores-Bautista
- Facultad de Estudios Superiores Zaragoza Campus II, Universidad Nacional Autónoma de México, Mexico City 09230, Mexico
| | - Silvia Laura Guzmán-Gutiérrez
- CONAHCYT/Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Ricardo Reyes-Chilpa
- Instituto de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Mayra León-Santiago
- Instituto de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Victor Manuel Luna-Pineda
- Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
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Osama DM, Zaki BM, Khalaf WS, Mohamed MYA, Tawfick MM, Amin HM. Occurrence and Molecular Study of Hypermucoviscous/Hypervirulence Trait in Gut Commensal K. pneumoniae from Healthy Subjects. Microorganisms 2023; 11:microorganisms11030704. [PMID: 36985277 PMCID: PMC10059952 DOI: 10.3390/microorganisms11030704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/02/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023] Open
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) is emerging worldwide. Hypermucoviscousity is the characteristic trait that distinguishes it from classic K. pneumoniae (cKp), which enables Kp to cause severe invasive infections. This research aimed to investigate the hypermucoviscous Kp (hmvKp) phenotype among gut commensal Kp isolated from healthy individuals and attempted to characterize the genes encoding virulence factors that may regulate the hypermucoviscosity trait. Using the string test, 50 identified Kp isolates from healthy individuals’ stool samples were examined for hypermucoviscosity and investigated by transmission electron microscopy (TEM). Antimicrobial susceptibility profiles of Kp isolates were determined using the Kirby Bauer disc method. Kp isolates were tested for genes encoding different virulence factors by PCR. Biofilm formation was assayed by the microtiter plate method. All Kp isolates were multidrug-resistant (MDR). Phenotypically, 42% of isolates were hmvKp. PCR-based genotypic testing revealed the hmvKp isolates belonged to capsular serotype K2. All study Kp isolates harbored more than one virulence gene. The genes magA and rmpA were not detected, while the terW gene was present in all isolates. The siderophores encoding genes entB and irp2 were most prevalent in hmvKp isolates (90.5%) and non-hmvKp (96.6%), respectively. hmvKp isolates harbored the genes wabG and uge with rates of 90.5% and 85.7%, respectively. The outcomes of this research highlight the potential health risk of commensal Kp to cause severe invasive diseases, owing to being hmvKp and MDR, and harboring multiple virulence genes. The absence of essential genes related to hypermucoviscosity such as magA and rmpA in hmvKp phenotypes suggests the multifactorial complexity of the hypermucoviscosity or hypervirulence traits. Thus, further studies are warranted to verify the hypermucoviscosity-related virulence factors among pathogenic and commensal Kp in different colonization niches.
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Affiliation(s)
- Dina M. Osama
- Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12451, Egypt; (D.M.O.); (B.M.Z.); (H.M.A.)
| | - Bishoy M. Zaki
- Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12451, Egypt; (D.M.O.); (B.M.Z.); (H.M.A.)
| | - Wafaa S. Khalaf
- Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11751, Egypt;
| | - Marwa Yousry A. Mohamed
- Biology Department, Faculty of Science, Kingdom of Saudi Arabia, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia;
| | - Mahmoud M. Tawfick
- Department of Microbiology and Immunology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11751, Egypt
- Department of Microbiology and Immunology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
- Correspondence:
| | - Heba M. Amin
- Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12451, Egypt; (D.M.O.); (B.M.Z.); (H.M.A.)
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Clonal transmission of polymyxin B-resistant hypervirulent Klebsiella pneumoniae isolates coharboring bla NDM-1 and bla KPC-2 in a tertiary hospital in China. BMC Microbiol 2023; 23:64. [PMID: 36882683 PMCID: PMC9990273 DOI: 10.1186/s12866-023-02808-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 02/24/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND The prevalence of multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKP) has gradually increased. It poses a severe threat to human health. However, polymyxin-resistant hvKP is rare. Here, we collected eight polymyxin B-resistant K. pneumoniae isolates from a Chinese teaching hospital as a suspected outbreak. RESULTS The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. HvKP was identified by detecting virulence-related genes and using a Galleria mellonella infection model. Their resistance to serum, growth, biofilm formation, and plasmid conjugation were analyzed in this study. Molecular characteristics were analyzed using whole-genome sequencing (WGS) and mutations of chromosome-mediated two-component systems pmrAB and phoPQ, and the negative phoPQ regulator mgrB to cause polymyxin B (PB) resistance were screened. All isolates were resistant to polymyxin B and sensitive to tigecycline; four were resistant to ceftazidime/avibactam. Except for KP16 (a newly discovered ST5254), all were of the K64 capsular serotype and belonged to ST11. Four strains co-harbored blaKPC-2, blaNDM-1, and the virulence-related genes prmpA, prmpA2, iucA, and peg344, and were confirmed to be hypervirulent by the G. mellonella infection model. According to WGS analysis, three hvKP strains showed evidence of clonal transmission (8-20 single nucleotide polymorphisms) and had a highly transferable pKOX_NDM1-like plasmid. KP25 had multiple plasmids carrying blaKPC-2, blaNDM-1, blaSHV-12, blaLAP-2, tet(A), fosA5, and a pLVPK-like virulence plasmid. Tn1722 and multiple additional insert sequence-mediated transpositions were observed. Mutations in chromosomal genes phoQ and pmrB, and insertion mutations in mgrB were major causes of PB resistance. CONCLUSIONS Polymyxin-resistant hvKP has become an essential new superbug prevalent in China, posing a serious challenge to public health. Its epidemic transmission characteristics and mechanisms of resistance and virulence deserve attention.
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Namikawa H, Oinuma KI, Yamada K, Kaneko Y, Kakeya H, Shuto T. Predictors of hypervirulent Klebsiella pneumoniae infections: a systematic review and meta-analysis. J Hosp Infect 2023; 134:153-160. [PMID: 36813165 DOI: 10.1016/j.jhin.2023.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/26/2023] [Accepted: 02/08/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND Hypervirulent Klebsiella pneumoniae (hvKp) infections confer notable morbidity and mortality. Differential diagnosis to determine whether the infections are caused by either the hvKp or classical K. pneumoniae (cKp) strain is particularly important for undertaking optimal clinical care and infection control efforts. AIM To identify and assess the potential predictors of hvKp infections. METHODS PubMed, Web of Science, and Cochrane Library databases were searched for all relevant publications from January 2000 to March 2022. The search terms included a combination of the following terms: (i) Klebsiella pneumoniae or K. pneumoniae and (ii) hypervirulent or hypervirulence. A meta-analysis of factors for which risk ratio was reported in three or more studies was conducted, and at least one statistically significant association was identified. FINDINGS In this systematic review of 11 observational studies, a total of 1392 patients with K. pneumoniae infection and 596 (42.8%) with hvKp strains were evaluated. In the meta-analysis, diabetes mellitus and liver abscess (pooled risk ratio: 2.61 (95% confidence interval: 1.79-3.80) and 9.04 (2.58-31.72), respectively; all P < 0.001) were predictors of hvKp infections. CONCLUSION For patients with a history of the abovementioned predictors, prudent management, including the search for multiple sites of infection and/or metastatic spread and the enforcement of an early and appropriate source control procedure, should be initiated in consideration of the potential presence of hvKp. We believe that this research highlights the urgent need for increasing clinical awareness of the management of hvKp infections.
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Affiliation(s)
- H Namikawa
- Department of Medical Education and General Practice, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan.
| | - K-I Oinuma
- Department of Bacteriology, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan; Research Center for Infectious Disease Sciences, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan
| | - K Yamada
- Research Center for Infectious Disease Sciences, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan; Department of Infection Control Science, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan
| | - Y Kaneko
- Department of Bacteriology, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan; Research Center for Infectious Disease Sciences, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan
| | - H Kakeya
- Research Center for Infectious Disease Sciences, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan; Department of Infection Control Science, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan
| | - T Shuto
- Department of Medical Education and General Practice, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan
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42
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[ST66 Hypervirulent Klebsiella pneumoniae as a cause of necrotizing pneumonia]. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2023; 41:134-136. [PMID: 36759053 DOI: 10.1016/j.eimce.2022.11.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/08/2022] [Indexed: 02/09/2023]
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Fernández Vecilla D, Unzaga Barañano MJ, García de Andoin Sojo C, Díaz de Tuesta Del Arco JL. [Cavitary pneumonia and sepsis caused by ST23 hypervirulent Klebsiella pneumoniae]. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2023; 41:129-131. [PMID: 36759051 DOI: 10.1016/j.eimce.2022.11.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/10/2022] [Indexed: 02/09/2023]
Affiliation(s)
- Domingo Fernández Vecilla
- Microbiología y Parasitología Clínica, Hospital Universitario de Basurto, Bilbao, Vizcaya, España; Biocruces Bizkaia Health Research Institute, Baracaldo, Vizcaya, España.
| | - Miren Josebe Unzaga Barañano
- Microbiología y Parasitología Clínica, Hospital Universitario de Basurto, Bilbao, Vizcaya, España; Biocruces Bizkaia Health Research Institute, Baracaldo, Vizcaya, España
| | - Carlota García de Andoin Sojo
- Biocruces Bizkaia Health Research Institute, Baracaldo, Vizcaya, España; Radiodiagnóstico, Hospital Universitario de Basurto, Bilbao, Vizcaya, España
| | - José Luis Díaz de Tuesta Del Arco
- Microbiología y Parasitología Clínica, Hospital Universitario de Basurto, Bilbao, Vizcaya, España; Biocruces Bizkaia Health Research Institute, Baracaldo, Vizcaya, España
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Chao CM, Lai CC, Yu WL. Epidemiology of extended-spectrum β-lactamases in Enterobacterales in Taiwan for over two decades. Front Microbiol 2023; 13:1060050. [PMID: 36762100 PMCID: PMC9905819 DOI: 10.3389/fmicb.2022.1060050] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 12/22/2022] [Indexed: 01/28/2023] Open
Abstract
The emergence of antimicrobial resistance among microorganisms is a serious public health concern, and extended-spectrum β-lactamases (ESBL)-producing Enterobacterales is one of the major concerns among antibiotic-resistant bacteria. Although the prevalence of ESBL in Enterobacterales has been increasing with time, the prevalence of ESBL could differ according to the species, hospital allocation, sources of infections, nosocomial or community acquisitions, and geographic regions. Therefore, we conducted a comprehensive review of the epidemiology of ESBL-producing Enterobacterales in Taiwan. Overall, the rates of ESBL producers are higher in northern regions than in other parts of Taiwan. In addition, the genotypes of ESBL vary according to different Enterobacterales. SHV-type ESBLs (SHV-5 and SHV-12) were the major types of Enterobacter cloacae complex, but Serratia marcescens, Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were more likely to possess CTX-M-type ESBLs (CTX-M-3 and CTX-M-14). Moreover, a clonal sequence type of O25b-ST131 has been emerging among urinary or bloodstream E. coli isolates in the community in Taiwan, and this clone was potentially associated with virulence, ESBL (CTX-M-15) production, ciprofloxacin resistance, and mortality. Finally, the evolution of the genetic traits of the ESBL-producing Enterobacterales isolates helps us confirm the interhospital and intrahospital clonal dissemination in several regions of Taiwan. In conclusion, continuous surveillance in the investigation of ESBL production among Enterobacterales is needed to establish its long-term epidemiology.
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Affiliation(s)
- Chien-Ming Chao
- Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan,Department of Dental Laboratory Technology, Min-Hwei College of Health Care Management, Tainan, Taiwan
| | - Chih-Cheng Lai
- Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Wen-Liang Yu
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan,Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan,*Correspondence: Wen-Liang Yu,
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Volozhantsev NV, Borzilov AI, Shpirt AM, Krasilnikova VM, Verevkin VV, Denisenko EA, Kombarova TI, Shashkov AS, Knirel YA, Dyatlov IA. Comparison of the therapeutic potential of bacteriophage KpV74 and phage-derived depolymerase (β-glucosidase) against Klebsiella pneumoniae capsular type K2. Virus Res 2022; 322:198951. [PMID: 36191686 DOI: 10.1016/j.virusres.2022.198951] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 09/16/2022] [Accepted: 09/29/2022] [Indexed: 12/24/2022]
Abstract
Bacteriophages and phage polysaccharide-degrading enzymes (depolymerases) are garnering attention as possible alternatives to antibiotics. Here, we describe the antimicrobial properties of bacteriophage KpV74 and phage depolymerase Dep_kpv74 specific to the hypervirulent Klebsiella pneumoniae of the K2 capsular type. The depolymerase Dep_kpv74 was identified as a specific glucosidase that cleaved the K2 type capsular polysaccharides of the K. pneumoniae by a hydrolytic mechanism. This depolymerase was effective against thigh soft tissue K. pneumoniae infection in mice without inducing adverse behavioral effects or toxicity. The depolymerase efficiency was similar to or greater than the bacteriophage efficiency. The phage KpV74 had a therapeutic effect only for treating the infection caused by the phage-propagating K. pneumoniae strain and was completely inactive against the infection caused by the K. pneumoniae strain that did not support phage multiplication. The depolymerase was effective in both cases. A mutant resistant to phage and depolymerase was isolated during the treatment of mice with bacteriophage. A confirmed one-base deletion in the flippase-coding wzx gene of this mutant is assumed to affect the polysaccharide capsule, abolishing the KpV74 phage adsorption and reducing the K. pneumoniae virulence.
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Affiliation(s)
- Nikolay V Volozhantsev
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia.
| | - Alexander I Borzilov
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
| | - Anna M Shpirt
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Valentina M Krasilnikova
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
| | - Vladimir V Verevkin
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
| | - Egor A Denisenko
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
| | - Tatyana I Kombarova
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
| | - Alexander S Shashkov
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Yuriy A Knirel
- N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Ivan A Dyatlov
- State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, City District Serpukhov, Moscow Region, Russia
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Kamau E, Ranson EL, Tsan AT, Bergmann-Leitner ES, Garner OB, Yang S. Clinical and genomic characterization of hypervirulent Klebsiella pneumoniae (hvKp) infections via passive surveillance in Southern California, 2020–2022. Front Microbiol 2022; 13:1001169. [PMID: 36312975 PMCID: PMC9614223 DOI: 10.3389/fmicb.2022.1001169] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Hypervirulent Klebsiella pneumoniae (hvKp) is more invasive and virulent than classical K. pneumoniae, and requires specialized treatment. To raise clinical awareness, this study determined the prevalence, clinical characteristics, and genomic epidemiology of hvKp infections in Southern California (SoCal) by conducting a passive surveillance in a single large academic medical center. We report here that hvKp infections were more common than expected, accounting for 2.6% of invasive K. pneumoniae infections, and presented with a wide disease spectrum, occasionally mimicking tumors, even co-infecting a COVID-19 patient. Most infections were community acquired with no recent international travel, suggesting hvKp strains are circulating in the community. Genomic analysis revealed genetic diversity, with the K1-ST23 lineage predominating but not clonal, and multiple sequence types of K2 including a SoCal unique K2-ST66 sublineage that had been unrecognized. Our findings highlight the urgency of heightened awareness of hvKp infection in the US, the need for rapid diagnosis of hvKp, and the necessity of implementing robust surveillance programs for hvKp at the institutional or local level.
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Affiliation(s)
- Edwin Kamau
- Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
| | - Elizabeth L. Ranson
- Division of Infectious Diseases, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
| | - Allison T. Tsan
- Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
| | - Elke S. Bergmann-Leitner
- Biologics Research and Development, Walter Reed Army Institute of Research, Silver Spring, MD, United States
| | - Omai B. Garner
- Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
| | - Shangxin Yang
- Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, United States
- *Correspondence: Shangxin Yang
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Chu HY, Chen LC, Kuo TR, Shih CC, Yougbaré S, Chen YH, Cheng TM. Haptoglobin-Conjugated Gold Nanoclusters as a Nanoantibiotic to Combat Bacteremia. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3596. [PMID: 36296784 PMCID: PMC9611519 DOI: 10.3390/nano12203596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/07/2022] [Accepted: 10/09/2022] [Indexed: 06/16/2023]
Abstract
Gold nanoclusters have revealed great potential as nanoantibiotics due to their superior chemical and physical characteristics. In this study, a peptide with 83 amino acids derived from haptoglobin was utilized as a surface ligand to synthesize gold nanoclusters via a facile hydrothermal approach. Characterization of the structural and optical properties demonstrated the successful synthesis of derived haptoglobin-conjugated gold nanoclusters. The spherical derived haptoglobin-conjugated gold nanoclusters exhibited a (111) plane of cubic gold and an ultra-small size of 3.6 ± 0.1 nm. The optical properties such as ultraviolet-visible absorption spectra, X-ray photoelectron spectroscopy spectra, fluorescence spectra, and Fourier transform infrared spectra also validated the successful conjugation between the derived haptoglobin peptide and the gold nanoclusters surface. The antibacterial activity, reactive oxygen species production, and antibacterial mechanisms of derived haptoglobin-conjugated gold nanoclusters were confirmed by culturing the bacterium Escherichia coli with hemoglobin to simulate bacteremia. The surface ligand of the derived haptoglobin peptide of derived haptoglobin-conjugated gold nanoclusters was able to conjugate with hemoglobin to inhibit the growth of Escherichia coli. The derived haptoglobin-conjugated gold nanoclusters with an ultra-small size also induced reactive oxygen species production, which resulted in the death of Escherichia coli. The superior antibacterial activity of derived haptoglobin-conjugated gold nanoclusters can be attributed to the synergistic effect of the surface ligand of the derived haptoglobin peptide and the ultra-small size. Our work demonstrated derived haptoglobin-conjugated gold nanoclusters as a promising nanoantibiotic for combating bacteremia.
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Affiliation(s)
- Hsiu-Yi Chu
- Graduate Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Lung-Ching Chen
- Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111045, Taiwan
| | - Tsung-Rong Kuo
- International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
| | - Chun-Che Shih
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan
- Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11230, Taiwan
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Sibidou Yougbaré
- Institut de Recherche en Sciences de La Santé/Direction Régionale du Centre Ouest (IRSS/DRCO), Nanoro BP 218, 11, Burkina Faso
| | - Yu-Han Chen
- Graduate Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Tsai-Mu Cheng
- Graduate Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan
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Phenotypic Characterization of Virulence Factors and Antibiogram of Klebsiella pneumoniae Isolates from Various Clinical Samples – A Cross Sectional Study. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.3.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
K. pneumoniae is known to cause hospital and community acquired infections. It is usually associated with upper & lower respiratory infections, septicaemia, urinary tract infection, wound infections, neonatal sepsis, meningitis, and endophthalmitis. The virulence factors play a role in its existence in different environmental conditions and therefore help in establishing Klebsiella pneumoniae infection in the human body. Multi drug resistant Klebsiella pneumoniae is an increasing threat to human health. Klebsiella pneumoniae is one of the species recognized as nosocomial pathogens that exhibit multidrug resistance and virulence in ESKAPE group as per WHO. The study was conducted to determine the various virulence factors & the antimicrobial pattern of Klebsiella pneumoniae isolates. A cross sectional observational study, conducted in Department of Microbiology of R.L. Jalappa Hospital and Research Centre, Kolar, Sample size of 150. All 150 Klebsiella pneumoniae isolates collected for the study, The Klebsiella pneumoniae isolates which were positive for various virulence factors were as follows on hemolysis 7(4.66%), capsule 150(100%), Hypermucoviscosity formation 66(44%), biofilm production 81(54%), siderophore production 110(73.33%), protease 135(90%), gelatinase 126(84%), lipase production 119(79.33%), lecithinase activity 82(54.66%). The drug resistance klebsiella pneumoniae were as follows: ESBL producers 24(16.67%), AmpC producers were 22(14.67%), MDR 116(74.20%), extensive drug resistant (XDR) 30(20%), pan drug resistant (PDR) 42(28%), Carbapenem resistance 65.33% reported. The increasing coexistence of virulence factors & antimicrobial resistance pattern is of particular concern. Hence active surveillance for antimicrobial resistance & virulence determinants is imperative now to implement effective control measures to prevent the rapid spread of drug resistance.
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Zandi R, Talebi S, Sheibani S, Ehsani A. Klebsiella pneumoniae and Enterobacter cloacae Induced Septic Arthritis in a Healthy Adolescent: A Rare Case Report. Hip Pelvis 2022; 34:185-190. [PMID: 36299475 PMCID: PMC9577308 DOI: 10.5371/hp.2022.34.3.185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/16/2022] [Accepted: 05/26/2022] [Indexed: 11/07/2022] Open
Abstract
Septic arthritis (SA) is a joint inflammation that develops secondary to infectious causes. SA in children is associated with a high rate of morbidity and mortality; therefore, it is regarded as an orthopedic emergency. Because SA of the hip joint usually mimics other musculoskeletal diseases, diagnosis remains challenging. Although this lesion usually shows a good outcome, treatment at an inappropriate time, neglect, or inadequate treatment could lead to poor outcomes. We report on the case of a healthy adolescent who complained of episodes of fever and chills, weight loss, pain in his left hip, and limping. After performing necessary workups, two differential diagnoses of tumor and SA were made. The results of Gram stain and culture of the synovial fluid after surgical excision showed Klebsiella pneumoniae and Enterobacter cloacae complex. To the best of our knowledge, this is the first report of SA due to co-infection with K. pneumoniae and E. cloacae in a healthy patient.
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Affiliation(s)
- Reza Zandi
- Department of Orthopedic Surgery, Taleghani Hospital Research Development Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahin Talebi
- Department of Orthopedic Surgery, Taleghani Hospital Research Development Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Sheibani
- Student Research Committee, School of Medicine, Mazandaran University of Medical Science, Sari, Iran
| | - Akbar Ehsani
- Department of Orthopedic Surgery, Taleghani Hospital Research Development Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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50
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Lin J, Huang Y, Qian L, Pan X, Song Y. Liver Abscess Combined with Endogenous Endophthalmitis Caused by Genotype ST25 Serotype K2 Hypervirulent Klebsiella pneumoniae: A Case Report. Infect Drug Resist 2022; 15:4557-4561. [PMID: 36003987 PMCID: PMC9393113 DOI: 10.2147/idr.s376443] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 08/02/2022] [Indexed: 11/23/2022] Open
Abstract
At present, invasive syndrome caused by hypervirulent Klebsiella pneumoniae (HvKp) is a widespread concern, and HvKp strains of different genotypes have been isolated. Here, we report a case of community-acquired liver abscess and endogenous endophthalmitis caused by a genotype ST25 serotype K2 (ST25-K2) HvKp strain in China. A 51-year-old man with diabetes was transferred to our hospital from a local community hospital with persistent fever for > 20 days and blurred vision in his left eye. A detailed examination revealed a liver abscess, endogenous endophthalmitis, and pneumonia. Bacterial cultures of pus from the liver abscess and the vitreous abscess of the left eye yielded Klebsiella pneumoniae (Kp), which was sensitive to the recommended drugs. In addition to positive string tests, a genetic analysis showed that the strain belonged to sequence type 25 (ST25) and serotype K2, and carried already-reported virulence genes, including iucA, rmpA2, rmpA, aerobactin, and entB. The pathogenic agent isolated from this patient was identified as HvKp. The patient’s general condition improved after a combination of treatments, including antimicrobial therapy, abscess drainage, and nutritional support. Unfortunately, the patient lost the vision in his left eye and developed secondary glaucoma, resulting in inevitable enucleation. Sequence 25 serotype K2 HvKp strains have been previously associated with nosocomial infections, but none associated with community-acquired liver abscess combined with endogenous endophthalmitis has yet been reported. Clinicians must be alert to the possibility of genotype ST25-K2 HvKp infection in patients with community-acquired liver abscess combined with an invasive infection, such as ocular discomfort.
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Affiliation(s)
- Jian Lin
- Department of Infectious Diseases, Tongling People's Hospital, Tongling, Anhui, 244000, People's Republic of China
| | - Yize Huang
- Department of Infectious Diseases, Tongling People's Hospital, Tongling, Anhui, 244000, People's Republic of China
| | - Li Qian
- Department of Ophthalmology, Tongling People's Hospital, Tongling, Anhui, 244000, People's Republic of China
| | - Xiaolong Pan
- Medical Laboratories, Tongling People's Hospital, Tongling, Anhui, 244000, People's Republic of China
| | - Youliang Song
- Department of Infectious Diseases, Tongling People's Hospital, Tongling, Anhui, 244000, People's Republic of China
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