Therapeutic strategies for infections by klebsiella pneumoniae carbapenem resistant: a narrative review

Authors

DOI:

https://doi.org/10.33448/rsd-v11i7.30296

Keywords:

Klebsiella pneumoniae carbapenemase; KPC-producing Enterobacteriae; KPC-KP Pathogenesis; KPC-KP laboratory diagnosis; Klebsiella pneumoniae treatment; Health teaching.

Abstract

Currently, bacterial infections with resistance patterns have been a major problem to be fought. In this scenario, the bacterium Klebsiella pneumoniae presents great importance due to its profile of multidrug resistance to antimicrobial drugs, through the production of enzymes with hydrolytic character, called carbapenemases. Because of this, it is necessary that the therapeutic protocols be reviewed for the satisfactory clinical evolution of patients, where knowing the pathogen's mechanisms of infection and its morphological characteristics elucidate which is the adequate therapeutic strategy. Thus, the objective of this work is to survey the literature on therapeutic strategies in infections by carbapenemase-producing K. pneumoniae, aiming at an analysis of the possibilities of treatment, comparing their benefits, weaknesses and possible impacts, as well as the application of new drugs in this theme. For this, a narrative bibliographic review was carried out, outlined by the search of articles, books and dissertations in the main electronic repositories. The descriptors used were: klebsiella pneumoniae carbapenemase; KPC-producing enterobacteriae; KPC-KP pathogenesis; KPC-KP laboratory diagnosis; Klebsiella pneumoniae treatment and health teaching. Finally, it was possible to observe that among the therapies used in infections by Klebsiella pneumoniae resistant to carbapenems, monotherapy tends to be ineffective, since this bacterium is multidrug resistant to conventional antimicrobial drugs. The use of combination therapy is more effective, due to the combined activity of the drugs in question. However, it is necessary that the physiological conditions of each patient be evaluated, given the high nephrotoxicity of some antimicrobials. As an addendum, new drugs also demonstrate significant efficacy for these infections.

References

Abrantes, J. A., Nogueira, J. M. R. (2017). The use of phenotypic tests for the research of carbapenamases in enterobacteria: a tool for clinical orientation. Escola Nacional de Saúde Pública Sérgio Arouca – ENSP/Fiocruz. Rio de Janeiro, RJ, Brasil. DOI: 10.21877/2448-3877.201700607.

Anvisa. Agência Nacional de Vigilância Sanitária. Prevenção de infecções por microrganismos multirresistentes em serviços de saúde. 1ª edição. 2021. Disponível em: https://bit.ly/3d78Ton. Acessado em 16/12/2021.

Bassetti, M., Giacobbe, D. R., Giamarellou, H., Viscoli, C., Daikos, G. L., Dimopoulos, G., De Rosa, F. G., Giamarellos-Bourboulis, E. J., Rossolini, G. M., Righi, E., Karaiskos, I., Tumbarello, M., Nicolau, D. P., Viale, P. L., Poulakou, G. (2018). Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Disease (ESCMID). Hellenic Society of Chemotherapy (HSC) and Società Italiana di Terapia Antinfettiva (SITA). Management of KPC-producing Klebsiella pneumoniae infections. Clin Microbiol Infect, 24(2), 133-144. Doi: 10.1016/j.cmi.2017.08.030.

Bassetti, M., Giacobbe, D. R., Patel, N., Tillotson, G., Massey, J. (2019). Efficacy and Safety of Meropenem-Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis. Adv Ther, 36(7), 1771-1777. Doi: 10.1007/s12325-019-00981-y.

Bassetti, M., McGovern, P. C., Wenish, C., Meyer, R. D., Yan, J. L., Wible, M., Rottinghaus, S. T., Quintana, A. (2015). Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials. Int J Antimicrob Agents, 46(3), 346-50. Doi: 10.1016/j.ijantimicag.2015.05.012.

Bassetti, M., Peghin, M., Pecori, D. (2016). The management of multidrug-resistant Enterobacteriaceae. Curr Opin Infect Dis, 29(6), 583-594. Doi: 10.1097/QCO.0000000000000314.

Bassetti, M., Peghin, M. (2020). How to manage KPC infections. Ther Adv Infect Dis, 14(7), 2049936120912049. Doi: 10.1177/2049936120912049.

Bertoncheli, C. M., Hörner, R. (2008). Uma revisão sobre metalo-β-lactamases. Revista Brasileira de Ciências Farmacêuticas [online], 44(4), 577-599. Doi: 10.1590/S1516-93322008000400005.

Cabral, A. B. (2011).Caracterização genética de isolados clínicos de Klebsiella pneumoniae resistentes a antibióticos β-lactâmicos de última geração provenientes de Recife-PE. Dissertação (especialização). Universidade Federal de Pernambuco. Pós- graduação em Medicina Tropical do Centro de Ciências da Saúde.

Cheng, W. L., Hsueh, P. R., Lee, C. C., Li, C. W., Li, M J., et al. (2016). Bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: Appropriateness of empirical treatment matters. Journal of Microbiology, Immunology and Infection, 49(2), 208-215. Doi: https://doi.org/10.1016/j.jmii.2014.05.003.

Czekster, A. L. (2017). Avaliação do perfil de sensibilidade e caracterização molecular de isolados de Klebsiella pneumoniae produtores de KPC isoladas de corrente sanguínea em quatro hospitais de Porto Alegre. Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre. Dissertação de Mestrado. Disponível em: https://www.lume.ufrgs.br/handle/10183/174721. Acesso em: 16/12/2021.

Daikos, G. L., Tsaousi, S., Tzouvelekis, L. S., Anyfantis, I., Psichogiou, M., Argyropoulou, A., Stefanou, I., Sypsa, V., Miriagou, V., Nepka, M., Georgiadou, S., Markogiannakis, A., Goukos, D., Skoutelis, A. (2014). Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother, 58(4), 2322-8. Doi: 10.1128/AAC.02166-13.

Galetti, R. (2010). Estudo de Pseudomonas aeruginosa produtoras de metalo-beta-lactamase e de genes envolvidos na resistência aos carbapenêmicos. Dissertação de Mestrado, Faculdade de Ciências Farmacêuticas de Ribeirão Preto – USP. Disponível em: https://www.teses.usp.br/teses/disponiveis/60/60135/tde-06102010-154221/publico/Dissertacao1.pdf.

Guimarães, D. O., Momesso, L. S., Tallarico, M. (2010). Antibióticos: importância terapêutica e perspectivas para a descoberta e desenvolvimento de novos agentes. Química Nova [online], 33(3), 667-679. DOI: 10.1590/S0100-40422010000300035. Acessado em: 16/12/2021.

Gutiérrez-Gutiérrez, B., Salamanca, E., De Cueto, M., et al. (2017). Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis, 17(7), 726-734. Doi: 10.1016/S1473-3099(17)30228-1.

Jeon, J. H., Lee, J. H., Lee, J. J., Park, K. S., Karim, A. M., Lee, C. R., Jeong, B. C. & Lee, S. H. (2015). Structural Basis for Carbapenem-Hydrolyzing Mechanisms of Carbapenemases Conferring Antibiotic Resistance. Int. J. Mol. Sci, 16, 9654-9692. Doi: https://doi.org/10.3390/ijms16059654.

Koneman, E. W., Allen, S. D., et al. (2001). Diagnóstico microbiológico texto e atlas colorido. Editora Médica e Científica, 1465. 5ª edição. Rio de Janeiro.

Lee, C. R., Lee, J. H., Park, K. S., K im, Y. B., Jeong, B. C., Lee, S. H. (2016). Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods. Front Microbiol, 7, 895. Doi: 10.3389/fmicb.2016.00895. Acessado em: 11/05/2022.

Lee, C. R., Lee, J. H., PARK, K. S., Jeon, J. H., K im, Y. B., Jeong, B. C., Lee, S. H. (2017). Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms. Front Cell Infect Microbiol, 21(7), 483. Doi: 10.3389/fcimb.2017.00483.

Li, J., Wang, W., Wang, G., Gu, G., Wu, X., Wang, Y., Huang, M., Li, J. (2018). Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections. Eur J Clin Microbiol Infect Dis, 37(4), 679-689. Doi: 10.1007/s10096-017-3160-z.

Li, W., Sun, G., Yu, Y., Li, N., Chen, M., Jin, R., Jiao, Y., Wu, H. (2014). Increasing occurrence of antimicrobial-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in China. Clin Infect Dis, 58(2), 225-32. Doi: 10.1093/cid/cit675.

Lu, B., Zhou, H., Zhang, X., Qu, M., Huang, Y., Wang, Q. (2017). Molecular characterization of Klebsiella pneumoniae isolates from stool specimens of outpatients in sentinel hospitals Beijing, China, 2010-2015. Gut Pathog, 30(9), 39. Doi: 10.1186/s13099-017-0188-7.

Martin, R. M. & Bachman, M. A. (2018). Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front Cell Infect Microbiol, 22(8), 4. Doi: 10.3389/fcimb.2018.00004.

Mitchell, J. M., Clasman, J. R., June, C. M., Kaitany, K. C., LaFleur, J. R., Taracila, M. A., Klinger, N. V., Bonomo, R. A., Wymore, T., Szarecka, A., Powers, R. A., & Leonard, D. A. (2015). Structural basis of activity against aztreonam and extended spectrum cephalosporins for two carbapenem-hydrolyzing class D β-lactamases from Acinetobacter baumannii. Biochemistry, 54(10), 1976–1987. Doi: https://doi.org/10.1021/bi501547k.

Munoz-Price, L. S., Poirel, L., Bonomo, R. A., Schwaber, M. J., et al. (2013). Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis, 13(9), 785-96. Doi: 10.1016/S1473-3099(13)70190-7.

Paczosa, M. K. & Mecsas, J. (2016). Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiol Mol Biol Rev, 80(3), 629-61. Doi: 10.1128/MMBR.00078-15.

Papp-Wallace, K. M., Endimiani, A., Taracila, M. A. & Bonomo, R. A. (2011). Carbapenems: past, present, and future. Antimicrobial Agents and Chemotherapy, 55(11), 4943-4960. DOI: 10.1128/aac.00296-11.

Pea, F., Siega, P. D., Cojutti, P., Sartor, A., Crapis, M., Bassetti, M. S. (2016). Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae? DOI: 10.1016/j.ijantimicag.2016.10.018. Acessado em: 09/05/2022.

Pereira, P. S., Borghi, M., de Araújo, C. F., Aires, C. A., Oliveira, J. C., Asensi, M. D., & Carvalho-Assef, A. P. (2015). Clonal Dissemination of OXA-370-Producing Klebsiella pneumoniae in Rio de Janeiro, Brazil. Antimicrobial agents and chemotherapy, 59(8), 4453–4456. https://doi.org/10.1128/AAC.04243-14.

Perez, F., El Chakhtoura, N. G., Yasmin, M., Bonomo, R. A. (2019). Polymyxins: To Combine or Not to Combine? DOI: 10.3390/antibiotics8020038.

Podschun, R. & Ullmann, U. (1998). Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev, 11(4), 589-603. Doi: 10.1128/CMR.11.4.589.

Reyes, J., Aguilar, A. C., Caicedo, A. (2019). Carbapenem-Resistant Klebsiella pneumoniae: Microbiology Key Points for Clinical Practice. Int J Gen Med, 28(12), 437-446. Doi: 10.2147/IJGM.S214305.

Ribeiro, S. M., de la Fuente-Núñez, C., Baquir, B., Faria-Junior, C., Franco, O. L., & Hancock, R. E. (2015). Antibiofilm peptides increase the susceptibility of carbapenemase-producing Klebsiella pneumoniae clinical isolates to β-lactam antibiotics. Antimicrobial agents and chemotherapy, 59(7), 3906–3912. https://doi.org/10.1128/AAC.00092-15.

Schirmer, A. A., Beccaria, C. S., Coser, H. S. (2020). CARBAPENEMASE PRODUCING ENTEROBACTERIA (KPC): ALTERNATIVES FOR CURRENT PHARMACOTHERAPY. Brazilian Journal of Surgery and Clinical Research – BJSCR, 33(3), 62-69. Disponível em: http://www.mastereditora.com.br/bjscr. Acessado em: 16/12/2021.

Seibert, G., Hörner, R., Meneghetti, B., Righi, R. A., Forno, N. L. F., Salla, A. (2014). Infecções hospitalares por enterobactérias produtoras de Klebsiella pneumoniae carbapenemase em um hospital escola. São Paulo. Einstein, 12(3), 282-286. Doi: https://doi.org/10.1590/s1679-45082014ao3131.

Shields, R. K., Nguyen, M. H., Chen, L., Press, E. G., Potoski, B. A, et al. (2017). Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia. Antimicrob Agents Chemother, 61(8), e00883-17. Doi: 10.1128/AAC.00883-17.

Silva, J. E. B. da, Souza, J. B. de, Macêdo, D. C. dos S., Barros, M. C. de S. A., Campos, L. A. de A., Costa Júnior, S. D. da., Ferraz Carvalho, R. de S., & Cavalcanti, I. M. F. (2022). Use of aminoglycosides as a therapeutic strategy to fight infections caused by Enterobacteriaceae that produce extended-spectrum β-lactamases. Research, Society and Development, 11(2), e57711225680. Doi: https://doi.org/10.33448/rsd-v11i2.25680.

Tortora, G. J., Funke, B. R. & Case, C. L. (2005). Microbiology: an introduction. 8º edition.

Tsuji, B. T., Pogue, J. M., Zavascki, A. P., Mical Paul, A. P., Daikos, G. L., et al. (2019). International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). DOI: 10.1002/phar.2209.

Tumbarello, M., Trecarichi, E. M., Corona, A. De Rosa, F. G., et al. (2019).Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis, 68(3), 355-364. Doi: 10.1093/cid/ciy492.

Tumbarello, M., Trecarichi, E. M., De Rosa, F. G., Giannella, M., et al. (2015). Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother, 70(7), 2133-43. Doi: 10.1093/jac/dkv086.

Tumbarello, M., Viale, P., Viscoli, C., et al. (2012). Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis, 55(7), 943-50. Doi: 10.1093/cid/cis588.

Wertheim H., Van Nguyen, K., Hara, G. L., Gelband, H., Laxminarayan, R., Mouton, R. & Cars, O. (2013). Global survey of polymyxin use: A call for international guidelines. Journal of Global Antimicrobial Resistance, 1(3), 131-134. Doi: https://doi.org/10.1016/j.jgar.2013.03.012.

Xie, J., Roberts, J. A., Alobaid, A. S., Roger, C., et al. (2017). Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections. Antimicrob Agents Chemother, 61(8), e00345-17. Doi: 10.1128/AAC.00345-17.

Yigit, H., Queenan, A. M., Anderson, G. J., Domenech-Sanchez, A., et al. (2001). Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother, 45(4), 1151-61. Doi: 10.1128/AAC.45.4.1151-1161.2001. Erratum in: Antimicrob Agents Chemother, 52(2), 809.

Zanol, F. C., Picoli, S. U., & Morsch, F. (2010). Detecção fenotípica de metalobetalactamase em isolados clínicos de Pseudomonas aeruginosa de hospitais de Caxias do Sul. Jornal Brasileiro de Patologia e Medicina Laboratorial [online], 46(4), 309-314. Doi: https://doi.org/10.1590/S1676-24442010000400008. Acessado 16/12/2021.

Published

31/05/2022

How to Cite

AFONSO, L. S. R. .; MILER-DA-SILVA, L. L.; GARRIDO, R. G. Therapeutic strategies for infections by klebsiella pneumoniae carbapenem resistant: a narrative review. Research, Society and Development, [S. l.], v. 11, n. 7, p. e46211730296, 2022. DOI: 10.33448/rsd-v11i7.30296. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/30296. Acesso em: 5 nov. 2024.

Issue

Section

Review Article