A profile of resistance in bacteria and the mechanisms associated due to the presence of the enzyme NDM-1: a systematic review

Perfil de resistencia a antibióticos en bacterias que presentan la enzima NDM-1 y sus mecanismos asociados: una revisión sistemática

In 2008 the NDM-1 enzyme was first reported, the enzyme responsible for the resistance to carbapenems. We conducted a systematic review to determine the resistance profile due to the presence of this enzyme in bacteria. We searched academic articles in principal databases resulting in the selection of 154 articles given our inclusion and exclusion criteria. 617 cases and 13 bacterial genera were reported in our sample. We find 4 resistance mechanisms which are principally resistant to beta-lactams and aminoglycosides. Hence, we have that the presence of the NDM-1 increases the likelihood of having genes that improves the bacteria’s resistance dramatically. The presence of the NDM-1 induces mechanisms which impacts the effectiveness of antibiotics and appropriate treatments are difficult to find.

1. Roca I, Akova M, Baquero F, Carlet J, Cavaleri M, Coenen S, et al. The global threat of antimicrobial resistance: Science for intervention. New Microbes New Infect. Elsevier Ltd; 2015;6(April 2015):22–9.
2. Grundmann H. Towards a global antibiotic resistance surveillance system: a primer for a roadmap. Ups J Med Sci. 2014;119(2):87–95.
3. Organización Mundial de la Salud. Antimicrobial Resistance Global Report on Surveillance 2014. [Internet] Disponible en: http://www.who.int/drugresistance/documents/AMR_report_ Web_slide_set.pdf?ua=1
4. Rasheed JK, Kitchel B, Zhu W, Anderson KF, Clark NC, Ferraro MJ, et al. New Delhi Metallo-β-Lactamase–producing Enterobacteriaceae, United States. Emerg Infect Dis. 2013;19(6):870–8.
5. Egger M, Smith GD AD. Systematic reviews in health care. Meta-analysis in context. BMJ Books. 2001.
6. Nordmann P, Poirel L, Carrër A, Toleman M a., Walsh TR. How to detect NDM-1 producers. J Clin Microbiol. 2011;49(2):718–21.
7. Arce-gil Z, Flores-clavo R. Deteccion del gen CTX-M en cepas de Escherichia coli productoras de betalactamasas de espectro extendido procedentes del hospital regional de lambayeque; Chiclayo-Perú: Noviembre 2012-Julio 2013. 2013;6(4):13–6.
8. González-Zorn B, Catalan A, Domínguez L, Teshager T, Porrero C, Moreno MA. Genetic basis for dissemination of armA. J Antimicrob Chemother. 2005;56(3):583–5.
9. Mosquito S, Ruiz J, Ochoa TJ. MECANISMOS MOLECULARES DE RESISTENCIA ANTIBIÓTICA EN Escherichia coli ASOCIADAS A DIARREA. Rev Peru Med Exp Salud Publica. 2011;28(4):9–11.
10. Jacoby G a. AmpC β-Lactamases. Clin Microbiol Rev. 2009;22(1):161–82.
11. Verdet C, Benzerara Y, Gautier V, Adam O, Ould-Hocine Z, Arlet G. Emergence of DHA-1-producing Klebsiella spp. in the Parisian region: Genetic organization of the ampC and ampR genes originating from Morganella morganii. Antimicrob Agents Chemother. 2006;50(2):607–17.
12. Yao Q, Zeng Z, Hou J, Deng Y, He L, Tian W, et al. Dissemination of the rmtB gene carried on IncF and IncN plasmids among Enterobacteriaceae in a pig farm and its environment. J Antimicrob Chemother. 2011;66(11):2475–9.
13. Hou J, Yang X, Zeng Z, Lv L, Yang T, Lin D, et al. Detection of the plasmid-encoded fosfomycin resistance gene fosA3 in Escherichia coli of food-animal origin. J Antimicrob Chemother. 2013;68(4):766–70.
14. Pournaras S, Tsakris A, Maniati M, Tzouvelekis LS, Maniatis AN. Novel Variant ( bla VIM-4 ) of the Metallo- β -Lactamase Gene bla VIM-1 in a Clinical Strain of Pseudomonas aeruginosa. Society. 2002;46(12):4026–8.
15. Kang M, Besser TE, Call DR. Variability in the Region Downstream of the bla CMY-2 β -Lactamase Gene in Escherichia coli and Salmonella enterica Plasmids. 2006;50(4):1590–3.
16. Ma L, Lin CJ, Chen JH, Fung CP, Chang FY, Lai YK, et al. Widespread dissemination of aminoglycoside resistance genes armA and rmtB in Klebsiella pneumoniae isolates in Taiwan producing CTX-M-type extended-spectrum B-lactamases. Antimicrob Agents Chemother. 2009;53(1):104–11.
17. Aminoglucósidos RA, Cepas EN, M LM, B GP, Ruiz - Parra AI, C YC, et al. DETERMINACIÓN DEL GEN aac(6´)aph(2´´) asociado con resistencia a aminoglucósidos en cepas de staphylococcus coagulasa negativa en una unidad neonatal en Bogotá. 2009;55:326–33.
18. Lidia Yolanda Fuchs, M.C. PD. LC. Mecanismos moleculares de la resistencia bacteriana. Salud Publica Mex. 1994;36(4):428–38.
19. Organizacion Panamericana de la salud organizacion mundial de la salud. Actualización Epidemiológica, carbapenemasas tipo New Delhi metalobetalactamasas (NDM). 2014: 1–3.
20. Shallcross LJ, Davies SC. The World Health Assembly resolution on antimicrobial resistance. J Antimicrob Chemother. 2014;69(11):2883–5.
21. Qin S, Fu Y, Zhang Q, Qi H, Wen JG, Xu H, et al. High incidence and endemic spread of NDM-1 positive Enterobacteriaceae in Henan province, China. Antimicrob Agents Chemother. 2014;58(8):4275–82.
22. Ageevets V a., Partina I V., Lisitsyna ES, Ilina EN, Lobzin Y V., Shlyapnikov S a., et al. Emergence of carbapenemaseproducing Gram-negative bacteria in Saint Petersburg, Russia. Int J Antimicrob Agents. Elsevier B.V. 2014;44(2):152–5.
23. Yong D, Toleman M a., Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-??-lactamase gene, bla NDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53(12):5046–54.
24. Jones LS, Toleman M a., Weeks JL, Howe R a., Walsh TR, Kumarasamy KK. Plasmid carriage of blaNDM-1in clinical Acinetobacter baumannii isolates from India. Antimicrob Agents Chemother. 2014;58(7):4211–3.
25. Collantes F. India: colonialismo, pobreza y estrategias de desarrollo. 1–34 [Internet]. Disponible en http://www.unizar. es/departamentos/estructura_economica/personal/collantf/ documents/India-Texto.pdf
26. Gaibani P, Ambretti S, Berlingeri a., Cordovana M, Farruggia P, Panico M, et al. Outbreak of NDM-1-producing Enterobacteriaceae in northern Italy, July to August 2011. Euro Surveill Bull Eur sur les Mal Transm = Eur Commun Dis Bull. 2011;16(47):2002.
27. Teo J, Ngan G, Balm M, Jureen R, Krishnan P, Lin R. Molecular characterization of NDM-1 producing Enterobacteriaceae isolates in Singapore hospitals. West Pacific Surveill Response. 2012;3(1):1–1.
28. Mulvey MR, Grant JM, Plewes K, Roscoe D, Boyd D a. New Delhi metallo-β-lactamase in Klebsiella pneumoniae and Escherichia coli, Canada. Emerg Infect Dis. 2011;17(1):103–6.
29. Mochon a. B, Garner OB, Hindler J a., Krogstad P, Ward KW,
30. Lewinski M a., et al. New Delhi metallo-β-lactamase (NDM1)-producing klebsiella pneumoniae: Case report and laboratory detection strategies. J Clin Microbiol. 2011;49(4):1667–70.
31. Carvalho-Assef APDA, Pereira PS, Albano RM, Berião GC, Chagas TPG, Timm LN, et al. Isolation of NDM-producing providencia rettgeri in brazil. J Antimicrob Chemother. 2013;68(12):2956–7.
32. Rozales FP, Ribeiro VB, Magagnin CM, Pagano M, Lutz L, Falci DR, et al. Emergence of NDM-1-producing Enterobacteriaceae in Porto Alegre, Brazil. Int J Infect Dis. 2014;25:79–81.
33. Carvalho-Assef APDA, Pereira PS, Albano RM, Berião GC, Tavares CP, Chagas TPG, et al. Detection of NDM-1-, CTX-M-15-, and qnrB4-producing enterobacter hormaechei isolates in Brazil. Antimicrob Agents Chemother. 2014;58(4):2475–6.
34. Barguigua A, Zerouali K, Katfy K, El Otmani F, Timinouni
35. M, Elmdaghri N. Occurrence of OXA-48 and NDM1 carbapenemase-producing Klebsiella pneumoniae in a Moroccan university hospital in Casablanca, Morocco. Infect Genet Evol. 2015;31:142–8. 34.
36. Escobar Pérez JA, Olarte Escobar NM, Castro-Cardozo B, Valderrama Márquez IA, Garzón Aguilar MI, De La Barrera LM, et al. Outbreak of NDM-1-producing Klebsiella pneumoniae in a neonatal unit in Colombia. Antimicrob Agents Chemother. 2013;57(4):1957–60.
37. Instituto Nacional de la Salud. Circular 1000 - 0057. [Internet]. 2012. Disponible en: http://www.ins.gov.co/ normatividad/Normatividad/circular 0057 de 2012.PDF
38. IQEN. Circulación de Carbapenemasas tipo New Delhi Metalo-β- lactamasa (NDM), Colombia, 2011 a 2013.
39. ;18(11):111–20. Disponible en: http://www.ins.gov. co:81/iqen/IQUEN/IQEN vol 18 2013 num 11.pdf
40. ANTIMICROBIAL RESISTANCE Global Report on
41. Surveillance 2014.Organizacion Mundial de la Salud. 2014.
42. Organización Mundial de la Salud. Hojas de información microbiológica. Guías para la Calid del agua potable [Internet]. 2008;191–241.Disponible en: http://www.who. int/water_sanitation_health/dwq/gdwq3_es_11.pdf
43. Isozumi R, Yoshimatsu K, Yamashiro T, Hasebe F, Nguyen BM, Ngo TC, et al. BlaNDM-1-positive Klebsiella pneumoniae from environment, Vietnam. Emerg Infect Dis. 2012;18(8):1383–5.
44. Kutumbaka KK, Han S, Mategko J, Nadala C, Buser GL, Cassidy MP, et al. Draft Genome Sequence of bla NDM-1 -Positive Escherichia coli O25b- ST131 Clone Isolated from an Environmental Sample. ASM. 2014;2(3):14–5.
45. Shaheen BW, Nayak R, Boothe DM. Emergence of a New Delhi metallo-β-Lactamase (NDM-1)-encoding gene in clinical Escherichia coli isolates recovered from companion animals in the United States. Antimicrob Agents Chemother. 2013;57(6):2902–3.
46. Barguigua A, El otmani F, Lakbakbi el yaagoubi F, Talmi M, Zerouali K, Timinouni M. First report of a Klebsiella pneumoniae strain coproducing NDM-1, VIM-1 and OXA-48 carbapenemases isolated in Morocco. Apmis. 2013;121(7):675–7.
47. Arpin C, Noury P, Boraud D, Coulange L, Manetti A, André C, et al. NDM-1-producing Klebsiella pneumoniae resistant to colistin in a French community patient without history of foreign travel. Antimicrob Agents Chemother. 2012;56(6):3432–4.
48. Castanheira M, Deshpande LM, Farrell SE, Shetye S, Shah N, Jones RN. Update on the prevalence and genetic characterization of NDM-1-producing Enterobacteriaceae in Indian hospitals during 2010. Diagn Microbiol Infect Dis. 2013;75(2):210–3.
49. Poirel L, Schrenzel J, Cherkaoui A, Bernabeu S, Renzi G, Nordmann P. Molecular analysis of NDM-1-producing enterobacterial isolates from Geneva, Switzerland. J Antimicrob Chemother. 2011;66(8):1730–3.
50. Stone NRH, Woodford N, Livermore DM, Howard J, Pike R, Mushtaq S, et al. Breakthrough bacteraemia due to tigecyclineresistant escherichia coli with New Delhi metallo-β-lactamase (NDM)-1 successfully treated with colistin in a patient with calciphylaxis. J Antimicrob Chemother. 2011;66(11):2677–8.
51. Li J, Lan R, Xiong Y, Ye C, Yuan M, Liu X, et al. Sequential Isolation in a Patient of Raoultella planticola and Escherichia coli Bearing a Novel ISCR1 Element Carrying blaNDM-1. PLoS One. 2014;9(3):e89893.
52. Savard P, Gopinath R, Zhu W, Kitchel B, Rasheed JK, Tekle T, et al. First NDM-positive Salmonella sp. strain identified in the United States. Antimicrob Agents Chemother. 2011;55(12):5957–8.
53. Fischer J, Schmoger S, Jahn S, Helmuth R, Guerra B. NDM-1 carbapenemase-producing Salmonella enterica subsp. enterica serovar Corvallis isolated from a wild bird in Germany. J Antimicrob Chemother. 2013;68(12):2954–6.
54. Zhang WJ, Lu Z, Schwarz S, Zhang RM, Wang XM, Si W, et al. Complete sequence of the blaNDM-1-carrying plasmid pNDM-AB from acinetobacter baumannii of food animal origin. J Antimicrob Chemother. 2013;68(7):1681–2.
55. Wang Y, Wu C, Zhang Q, Qi J, Liu H, Wang Y, et al. Identification of New Delhi metallo-β-lactamase 1 in acinetobacter Lwoffii of food animal origin. PLoS One. 2012;7(5):3–8.
56. Lascols C, Hackel M, Marshall SH, Hujer AM, Bouchillon S, Badal R, et al. Increasing prevalence and dissemination of NDM-1 metallo-β-lactamase in India: Data from the SMART study (2009). J Antimicrob Chemother. 2011;66(9):1992–7.
57. Kumarasamy K, Kalyanasundaram A. Emergence of klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India. J Antimicrob Chemother. 2012;67(1):243–4.
58. Bonnin R. A., Cuzon G, Poirel L, Nordmann P. Multidrugresistant Acinetobacter baumannii clone, France. Emerg Infect Dis. 2013;19(5):822–3.
59. Bakour S, Touati A, Bachiri T, Sahli F, Tiouit D, Naim M, et al. First report of 16S rRNA methylase ArmA-producing Acinetobacter baumannii and rapid spread of metallo-βlactamase NDM-1 in Algerian hospitals. J Infect Chemother. 2014;20(11):696–701.
60. García CS, de la Gándara MP, García FJC. Betalactamasas de espectro extendido en enterobacterias distintas de Escherichia coli y Klebsiella. Enferm Infecc Microbiol Clin. Elsevier; 2010;28(SUPPL. 1):12–8.
61. Qu H, Wang X, Ni Y, Liu J, Tan R, Huang J, et al. NDM1-producing Enterobacteriaceae in a teaching hospital in Shanghai, China: IncX3-type plasmids may contribute to the dissemination of blaNDM-1. Int J Infect Dis. International Society for Infectious Diseases. 2015;34:8–13.
62. Williamson D a., Sidjabat HE, Freeman JT, Roberts S a., Silvey A, Woodhouse R, et al. Identification and molecular characterisation of New Delhi metallo-??-lactamase-1 (NDM1)- and NDM-6-producing Enterobacteriaceae from New Zealand hospitals. Int J Antimicrob Agents. Elsevier B.V. 2012;39(6):529–33.
63. Gefen-Halevi S, Hindiyeh MY, Ben-David D, Smollan G, Gal-Mor O, Azar R, et al. Isolation of genetically unrelated blandm-1-positive providencia rettgeri strains in israel. J Clin Microbiol. 2013;51(5):1642–3.
64. Khajuria A, Praharaj AK, Kumar M, Grover N. Emergence of NDM - 1 in the clinical isolates of Pseudomonas aeruginosa in India. J Clin Diagnostic Res. 2013;7(7):1328–31.
65. Santiago MA, Esquirol JL, Fernández RN, Maletá PD. Aminoglucósidos: Mirada actual desde su historia. Rev Cubana Pediatr. 2007;79(2).
66. Grünbaum F. Resistencia a aminoglucósidos en ENTEROBACTERIACEAE. Universidad Autonoma de Barcelona. [Internet]. 2011. Disponible en: http://www.tdx.cat/bitstream/ handle/10803/42291/fg1de1.63.
67. Leyva S, Leyva E. Fluoroquinolonas. Mecanismos de acción y resistencia, estructura, síntesis y reacciones fisicoquímicas importantes para propiedades medicinales. Boletín la Soc Química México. 2008;2(1):1–13.
68. Rodríguez-Martínez JM. Mecanismos de resistencia a quinolonas mediada por plásmidos. Enferm Infecc Microbiol Clin. 2005;23(1):25–31.
69. Butler CC, Hood K, Verheij T, Little P, Melbye H, Nuttall J, Kelly MJ, Mölstad S GM, Almirall J, Torres A, Cals JWL, Butler CC, Hopstaken RM, Hood K DG. Informe Resistencia Bacteriana. [Internet]. 2013. Disponible en: http://www. portalfarma.com/Profesionales/comunicacionesprofesionales/ informes-tecnico-profesionales/Documents/Informe_Resistencia_Bacteriana_PF79.pdf
70. Páez, L. C. C., et al. (2015). “Comparación del cultivo celular de HeLa y HEp-2: Perspectivas de estudios con Chlamydia trachomatis.” Nova 13(23).
71. Corrales, L. C., et al. (2015). “Bacterias anaerobias: procesos que realizan y contribuyen a la sostenibilidad de la vida en el planeta.” Nova 13(24): 55-82.
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73. DOI: http://dx.doi.org/10.22490/24629448.1733