Microbiological Characterization of KPC-Producing Klebsiella Pneumoniae: A Systematic Review
Main Article Content
Abstract
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic bacterium that causes nosocomial infections and usually affects people with malfunctioning immune systems. These bacteria can also cause potentially fatal community-acquired diseases. A high fatality rate has been documented in carbapenem-resistant K. pneumoniae, particularly carbapenemase-producing cases. This is due to few antibiotic therapy choices. This study aims to assess the microbiological characteristics of KPC-K. pneumoniae in terms of their genotypic features. This article reported a systematic review that used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines to identify articles related to carbapenem-resistant K. pneumoniae. Pubmed and SagePub, two online databases, were searched using pre-established inclusion and exclusion criteria. The search turned up six studies that showed K. pneumoniae contains numerous gene mutations that cause carbapenem resistance, including blaKPC, blaKPC-2, blaKPC-3, and blaKPC-23. The mutations in porins OmpK35, OmpK36, and OmpK37 also significantly contribute to this resistance. These findings indicated that the optimal combination of antibiotics should be tailored to the specific strain of K. pneumoniae with a carbapenem-resistant genotype, especially for KPC-Kp strains with a mutation in OmpK36. The findings of this systematic review offer vital information for creating successful strategies to fight carbapenem-resistant K. pneumoniae infections.
Article Details
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
References
Abou-assy, R. S., Aly, M. M., Amasha, R. H., Jastaniah, S., Alammari, F., & Shamrani, M. (2023). Carbapenem resistance mechanisms, carbapenemase genes dissemination, and laboratory detection methods: a review. International Journal of Pharmaceutical Research and Allied Sciences, 12(1-2023), 123-138.
Alvisi, G., Curtoni, A., Fonnesu, R., Piazza, A., Signoretto, C., Piccinini, G., ... & Gaibani, P. (2025). Epidemiology and genetic traits of carbapenemase-producing enterobacterales: A global threat to human health. Antibiotics, 14(2), 141. https://doi.org/10.3390/antibiotics14020141
Campos, A. C., Albiero, J., Ecker, A. B., Kuroda, C. M., Meirelles, L. E., Polato, A., ... & Teixeira, J. J. (2016). Outbreak of Klebsiella pneumoniae carbapenemase–producing K pneumoniae: A systematic review. American Journal of Infection Control, 44(11), 1374-1380. https://doi.org/10.1016/j.ajic.2016.03.022
Cannatelli, A., Di Pilato, V., Giani, T., Arena, F., Ambretti, S., Gaibani, P., ... & Rossolini, G. M. (2014). In vivo evolution to colistin resistance by PmrB sensor kinase mutation in KPC-producing Klebsiella pneumoniae is associated with low-dosage colistin treatment. Antimicrobial agents and chemotherapy, 58(8), 4399-4403. https://doi.org/10.1128/aac.02555-14
Castanheira, M., Simner, P. J., & Bradford, P. A. (2021). Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection. JAC-antimicrobial resistance, 3(3), dlab092. https://doi.org/10.1093/jacamr/dlab092
Clancy, C. J., Chen, L., Hong, J. H., Cheng, S., Hao, B., Shields, R. K., ... & Nguyen, M. H. (2013). Mutations of the ompK36 porin gene and promoter impact responses of sequence type 258, KPC-2-producing Klebsiella pneumoniae strains to doripenem and doripenem-colistin. Antimicrobial agents and chemotherapy, 57(11), 5258-5265. https://doi.org/10.1128/aac.01069-13
Du, Y., Mu, S., Liu, Y., Yuan, Y., Zhu, Y., Ma, L., ... & Wang, S. (2022). The genomic characterization of KPC-producing Klebsiella pneumoniae from the ICU of a Teaching Hospital in Shanghai, China. Infection and Drug Resistance, 69-81. https://doi.org/10.2147/IDR.S343673
Falagas, M. E., Asimotou, C. M., Zidrou, M., Kontogiannis, D. S., & Filippou, C. (2025). Global epidemiology and antimicrobial resistance of Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative clinical isolates: a review. Microorganisms, 13(7), 1697. https://doi.org/10.3390/microorganisms13071697
Follador, R., Heinz, E., Wyres, K. L., Ellington, M. J., Kowarik, M., Holt, K. E., & Thomson, N. R. (2016). The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial genomics, 2(8), e000073. https://doi.org/10.1099/mgen.0.000073
Gaibani, P., Amadesi, S., Lazzarotto, T., & Ambretti, S. (2022). Genome characterization of a Klebsiella pneumoniae co-producing OXA-181 and KPC-121 resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and cefiderocol isolated from a critically ill patient. Journal of Global Antimicrobial Resistance, 30, 262-264. https://doi.org/10.1016/j.jgar.2022.06.021
Gaibani, P., Re, M. C., Campoli, C., Viale, P. L., & Ambretti, S. (2020). Bloodstream infection caused by KPC-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam: epidemiology and genomic characterization. Clinical Microbiology and Infection, 26(4), 516-e1. https://doi.org/10.1016/j.cmi.2019.11.011
Galani, I., Antoniadou, A., Karaiskos, I., Kontopoulou, K., Giamarellou, H., & Souli, M. (2019). Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. Clinical Microbiology and Infection, 25(6), 763-e5. https://doi.org/10.1016/j.cmi.2019.03.011
García, P., Brito, B., Alcalde-Rico, M., Munita, J. M., Martínez, J. R., Olivares-Pacheco, J., ... & Wozniak, A. (2022). Acquisition of resistance to ceftazidime-avibactam during infection treatment in Pseudomonas aeruginosa through D179Y mutation in one of two blaKPC-2 gene copies without losing carbapenem resistance. Frontiers in Cellular and Infection Microbiology, 12, 981792. https://doi.org/10.3389/fcimb.2022.981792
Giddins, M. J., Macesic, N., Annavajhala, M. K., Stump, S., Khan, S., McConville, T. H., ... & Uhlemann, A. C. (2018). Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in bla KPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrobial agents and chemotherapy, 62(3), 10-1128. https://doi.org/10.1128/aac.02101-17
Hobson, C. A., Pierrat, G., Tenaillon, O., Bonacorsi, S., Bercot, B., Jaouen, E., ... & Birgy, A. (2022). Klebsiella pneumoniae carbapenemase variants resistant to ceftazidime-avibactam: an evolutionary overview. Antimicrobial agents and chemotherapy, 66(9), e00447-22. https://doi.org/10.1128/aac.00447-22
Hu, Y., Anes, J., Devineau, S., & Fanning, S. (2021). Klebsiella pneumoniae: prevalence, reservoirs, antimicrobial resistance, pathogenicity, and infection: a hitherto unrecognized zoonotic bacterium. Foodborne pathogens and disease, 18(2), 63-84. https://doi.org/10.1089/fpd.2020.284
Jelic, M., Butic, I., Plecko, V., Cipris, I., Jajic, I., Bejuk, D., ... & Andrasevic, A. T. (2016). KPC-producing Klebsiella pneumoniae isolates in Croatia: a nationwide survey. Microbial drug resistance, 22(8), 662-667. https://doi.org/10.1089/mdr.2015.0150
Jin, X., Chen, Q., Shen, F., Jiang, Y., Wu, X., Hua, X., ... & Yu, Y. (2021). Resistance evolution of hypervirulent carbapenem-resistant Klebsiella pneumoniae ST11 during treatment with tigecycline and polymyxin. Emerging microbes & infections, 10(1), 1129-1136. https://doi.org/10.1080/22221751.2021.1937327
Karampatakis, T., Tsergouli, K., & Behzadi, P. (2023). Carbapenem-resistant Klebsiella pneumoniae: virulence factors, molecular epidemiology and latest updates in treatment options. Antibiotics, 12(2), 234. https://doi.org/10.3390/antibiotics12020234
Ke, Y., Zeng, Z., Liu, J., & Ye, C. (2025). Capsular polysaccharide as a potential target in hypervirulent and drug-resistant Klebsiella pneumoniae treatment. Infection and Drug Resistance, 1253-1262. https://doi.org/10.2147/IDR.S493635
Ko, K. S. (2017). The contribution of capsule polysaccharide genes to virulence of Klebsiella pneumoniae. Virulence, 8(5), 485-486. https://doi.org/10.1080/21505594.2016.1240862
Lee, C. R., Lee, J. H., Park, K. S., Kim, Y. B., Jeong, B. C., & Lee, S. H. (2016). Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Frontiers in microbiology, 7, 895. https://doi.org/10.3389/fmicb.2016.00895
Li, B., Zhao, Y., Liu, C., Chen, Z., & Zhou, D. (2014). Molecular pathogenesis of Klebsiella pneumoniae. Future microbiology, 9(9), 1071-1081. https://doi.org/10.2217/fmb.14.48
Livermore, D. M., Warner, M., Jamrozy, D., Mushtaq, S., Nichols, W. W., Mustafa, N., & Woodford, N. (2015). In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrobial agents and chemotherapy, 59(9), 5324-5330.
Lomovskaya, O., Sun, D., Rubio-Aparicio, D., Nelson, K., Tsivkovski, R., Griffith, D. C., & Dudley, M. N. (2017). Vaborbactam: spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrobial agents and chemotherapy, 61(11), 10-1128. https://doi.org/10.1128/aac.01443-17
Luo, M., Yang, X. X., Tan, B., Zhou, X. P., Xia, H. M., Xue, J., ... & Li, Y. L. (2016). Distribution of common pathogens in patients with pyogenic liver abscess in China: a meta-analysis. European Journal of Clinical Microbiology & Infectious Diseases, 35(10), 1557-1565. https://doi.org/10.1007/s10096-016-2712-y
Martin, R. M., & Bachman, M. A. (2018). Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Frontiers in cellular and infection microbiology, 8, 4. https://doi.org/10.3389/fcimb.2018.00004
Mehta, S. C., Rice, K., & Palzkill, T. (2015). Natural variants of the KPC-2 carbapenemase have evolved increased catalytic efficiency for ceftazidime hydrolysis at the cost of enzyme stability. PLoS pathogens, 11(6), e1004949. https://doi.org/10.1371/journal.ppat.1004949
Mohammadpour, D., Memar, M. Y., Leylabadlo, H. E., Ghotaslou, A., & Ghotaslou, R. (2025). Carbapenem-Resistant Klebsiella pneumoniae: A comprehensive review of phenotypic and genotypic methods for detection. The Microbe, 6, 100246. https://doi.org/10.1016/j.microb.2025.100246
Mohd Asri, N. A., Ahmad, S., Mohamud, R., Mohd Hanafi, N., Mohd Zaidi, N. F., Irekeola, A. A., ... & Yusof, N. Y. (2021). Global prevalence of nosocomial multidrug-resistant Klebsiella pneumoniae: a systematic review and meta-analysis. Antibiotics, 10(12), 1508. https://doi.org/10.3390/antibiotics10121508
Munoz-Price, L. S., Poirel, L., Bonomo, R. A., Schwaber, M. J., Daikos, G. L., Cormican, M., ... & Quinn, J. P. (2013). Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. The Lancet infectious diseases, 13(9), 785-796.
Paczosa, M. K., & Mecsas, J. (2016). Klebsiella pneumoniae: going on the offense with a strong defense. Microbiology and molecular biology reviews, 80(3), 629-661. https://doi.org/10.1128/mmbr.00078-15
Piper, B. J., Alinea, A. A., Wroblewski, J. R., Graham, S. M., Chung, D. Y., McCutcheon, L. R., ... & Bordonaro, M. (2019). A quantitative and narrative evaluation of Goodman and Gilman’s Pharmacological Basis of Therapeutics. Pharmacy, 8(1), 1. https://doi.org/10.3390/pharmacy8010001
Pitout, J. D., Nordmann, P., & Poirel, L. (2015). Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrobial agents and chemotherapy, 59(10), 5873-5884. https://doi.org/10.1128/aac.01019-15
Rendueles, O. (2020). Deciphering the role of the capsule of Klebsiella pneumoniae during pathogenesis: A cautionary tale. Molecular microbiology, 113(5), 883-888. https://doi.org/10.1111/mmi.14474Digital Object Identifier (DOI)
Reyes, J., Aguilar, A. C., & Caicedo, A. (2019). Carbapenem-resistant Klebsiella pneumoniae: microbiology key points for clinical practice. International journal of general medicine, 437-446. https://doi.org/10.2147/IJGM.S214305
Sahly, H., Podschun, R., & Ullmann, U. (2002). Klebsiella infections in the immunocompromised host. The biology and pathology of innate immunity mechanisms, 237-249. https://doi.org/10.1007/0-306-46831-X_21
Santino, I., Bono, S., Nuccitelli, A., Martinelli, D., Petrucci, C., & Alari, A. (2013). Microbiological and molecular characterization of extreme drug-resistant carbapenemase-producing Klebsiella pneumoniae isolates. International Journal of Immunopathology and Pharmacology, 26(3), 785-790. https://doi.org/10.1177/039463201302600325
Satlin, M. J., Chen, L., Patel, G., Gomez-Simmonds, A., Weston, G., Kim, A. C., ... & Kreiswirth, B. N. (2017). Multicenter clinical and molecular epidemiological analysis of bacteremia due to carbapenem-resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States. Antimicrobial agents and chemotherapy, 61(4), 10-1128. https://doi.org/10.1128/aac.02349-16
Shields, R. K., Chen, L., Cheng, S., Chavda, K. D., Press, E. G., Snyder, A., ... & Clancy, C. J. (2017). Emergence of ceftazidime-avibactam resistance due to plasmid-borne bla KPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrobial agents and chemotherapy, 61(3), 10-1128. https://doi.org/10.1128/aac.02097-16
Songsantiphap, C., Vanichanan, J., Chatsuwan, T., Asawanonda, P., & Boontaveeyuwat, E. (2022). Methylene blue–mediated antimicrobial photodynamic therapy against clinical isolates of extensively drug resistant gram-negative Bacteria causing nosocomial infections in Thailand, an in vitro study. Frontiers in cellular and infection microbiology, 12, 929242. https://doi.org/10.3389/fcimb.2022.929242
Sun, D., Rubio-Aparicio, D., Nelson, K., Dudley, M. N., & Lomovskaya, O. (2017). Meropenem-vaborbactam resistance selection, resistance prevention, and molecular mechanisms in mutants of KPC-producing Klebsiella pneumoniae. Antimicrobial agents and chemotherapy, 61(12), 10-1128. https://doi.org/10.1128/aac.01694-17
Tsai, C. C., Lin, J. C., Chen, P. C., Liu, E. Y. M., Tsai, Y. K., Yu, C. P., ... & Siu, L. K. (2023). A 20-year study of capsular polysaccharide seroepidemiology, susceptibility profiles, and virulence determinants of Klebsiella pneumoniae from bacteremia patients in Taiwan. Microbiology Spectrum, 11(3), e00359-23. https://doi.org/10.1128/spectrum.00359-23
Tsivkovski, R., & Lomovskaya, O. (2020). Potency of vaborbactam is less affected than that of avibactam in strains producing KPC-2 mutations that confer resistance to ceftazidime-avibactam. Antimicrobial agents and chemotherapy, 64(4), 10-1128. https://doi.org/10.1128/aac.01936-19
Tzouvelekis, L. S., Markogiannakis, A., Psichogiou, M., Tassios, P. T., & Daikos, G. L. (2012). Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clinical microbiology reviews, 25(4), 682-707. https://doi.org/10.1128/cmr.05035-11