Current treatment options for infections caused by carbapenem-resistant Enterobacteriaceae in patients with hematological malignancies

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Abstract

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties.

About the authors

G. A. Klyasova

National Research Center for Hematology, Ministry of Health of Russia

Author for correspondence.
Email: klyasova.g@blood.ru
ORCID iD: 0000-0001-5973-5763

4 Novyy Zykovskiy Proezd, Moscow 125167

Russian Federation

References

  1. Klyasova G.A. Antimicrobial therapy. In: Program treatment of blood system diseases: collection of diagnostic algorithms and protocols for the treatment of blood system disorders. Ed.: V.G. Savchenko. Moscow: Praktika, 2012. Pp. 827–54. (In Russ.).
  2. Klyasova G.A., Speranskaya L.L., Mironova A.V. et al. The pathogens causing sepsis in immunocompromised patients: structure and problems of antibiotic resistance. Results of multicenter cooperative study. Gematologiya i transfuziologiya = Hematology and Transfusiology 2007;52(1):11–8. (In Russ.).
  3. Puerta-Alcalde P., Cardozo C., Marco F. et al. Changing epidemiology of bloodstream infection in a 25-years hematopoietic stem cell transplant program: current challenges and pitfalls on empiric antibiotic treatment impacting outcomes. Bone Marrow Transplant 2020;55(3):603–12. doi: 10.1038/s41409-019-0701-3.
  4. Klyasova G.A., Okhmat V.A. Antimicrobial therapy. In: Diagnostic algorithms and protocols for the treatment of blood system disorders. Ed.: V.G. Savchenko. Moscow: Praktika 2018. T. 2. Pp. 1067–1114. (In Russ.).
  5. De Angelis G., Fiori B., Menchinelli G. et al. Incidence and antimicrobial resistance trends in bloodstream infections caused by ESKAPE and Escherichia coli at a large teaching hospital in Rome, a 9-year analysis (2007-2015). Eur J Clin Microbiol Infect Dis 2018;37(9):1627–36. doi: 10.1007/s10096-018-3292-9.
  6. Pouch S.M., Satlin M.J. Carbapenemresistant Enterobacteriaceae in special populations: solid organ transplant recipients, stem cell transplant recipients, and patients with hematologic malignancies. Virulence 2017;8(4):391–402. doi: 10.1080/21505594.2016.1213472.
  7. Girmenia C., Rossolini G.M., Piciocchi A. et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant 2015;50(2):282–8. doi: 10.1038/bmt.2014.231.
  8. Trecarichi E.M., Pagano L., Martino B. et al. Bloodstream infections caused by Klebsiella pneumoniae in oncohematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol 2016;91(11):1076–81. doi: 10.1002/ajh.24489.
  9. Klyasova G., Korobova A., Khrulnova S. et al. Trends in antimicrobial resistance in gram-negative pathogens among haematological patients: results of multicenter study. Abstract Book 2020 European Congress of Clinical Microbiology and Infectious Diseases 2020;4:4253.
  10. Averbuch D., Tridello G., Hoek J. et al. Antimicrobial resistance in gram-negative rods causing bacteremia in hematopoietic stem cell transplant recipients: Intercontinental prospective study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin Infect Dis 2017;13;65(11):1819–28. doi: 10.1093/cid/cix646.
  11. Ambler R.P. The structure of betalactamases. Philos Trans R Soc Lond B Biol Sci 1980;289(1036):321–31.
  12. Sukhorukova M.V., Edelstein M.V., Ivanchik N.V. et al. Antimicrobial resistance of nosocomial Enterobacterales isolates in Russia: results of multicenter epidemiological study “MARATHON 2015–2016”. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2019;21(2):147–59. (In Russ.). doi: 10.36488/cmac.2019.2.147-159.
  13. Tzouvelekis L., Markogiannakis A., Psichogiou M. et al. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: anevolving crisis of global dimensions. Clin Microbiol Rev 2012;25:682–707. doi: 10.1128/CMR.05035-11.
  14. Rodríguez-Bano J., Cisneros J.M., Cobos-Triguerosd N. et al. Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin 2015;33(5):337.e1–21. doi: 10.1016/j.eimc.2014.11.009.
  15. De Maio Carrilho C.M.D., Marques de Oliveira L., Gaudereto J. et al. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome. BMC Infect Dis 2016;16:629. doi: 10.1186/s12879-016-1979-z.
  16. Tumbarello M., Trecarichi E.M., De Rosa F.G. et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 2015;70(7):2133–43. doi: 10.1093/jac/dkv086.
  17. Gutiérrez-Gutiérrez B., Salamanca E., de Cueto M. et al. 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 2017;7:726–34. doi: 10.1016/S14733099(17)302281.
  18. Akova M., Daikos G.L., Tzouvelekis L., Carmeli Y. Interventional strategies and current clinical experience with carbapenemase-producing gram-negative bacteria. Clin Microbiol Infect 2012;18(5):439–48. doi: 10.1111/j.1469-0691.2012.03823.x.
  19. Daikos G.L., Tsaousi S., Tzouvelekis L.S. et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 2014;58(4):2322–8. doi: 10.1128/AAC.02166-13.
  20. Endimiani A., Perez F., Bajaksouzian S. et al. Evaluation of updated interpretative criteria for categorizing Klebsiella pneumoniae with reduced carbapenem susceptibility. J Clin Microbiol 2010;48(12):4417–25. doi: 10.1128/JCM.02458-09.
  21. Daikos G.L., Markogiannakis A. Carbapenemase-producing Klebsiella pneumoniae: (When) might we still consider treating with carbapenems? Clin Microbiol Infect 2011;17(8):1135–41. doi: 10.1111/j.1469-0691.2011.03553.x.
  22. Beloborodov V.B., Gruver K.P. Carbapenems in modern clinical practice. Russkiy meditsinskiy zhurnal = Russian Medical Journal 2012;18(17):1037–42. (In Russ.).
  23. Sheu C.C., Chang Y.T., Lin S.Y. et al. Infections caused by carbapenem-resistant Enterobacteriaceae: an update on therapeutic options. Front Microbiol 2019;30;10:80. doi: 10.3389/fmicb.2019.00080.
  24. Tsuji B.T., Pogue J.M., Zavascki A.P. et al. 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). Pharmacotherapy 2019;39(1):10–39. doi: 10.1002/phar.2209.
  25. Bassetti M., Giacobbe D.R., Giamarellou H. et al. Management of KPC-producing Klebsiella pneumoniae infections. Clin Microbiol Infect 2018;24(2):133–44. doi: 10.1016/j.cmi.2017.08.030.
  26. Mashni O., Nazer L., Le J. Critical review of double-carbapenem therapy for the treatment of carbapenemaseproducing Klebsiella pneumoniae. Ann Pharmacother 2019;53(1):70–81. doi: 10.1177/1060028018790573.
  27. Roberts J.A., Abdul-Aziz M.H., Davis J.S. et al. Continuous versus intermittent β-lactam infusion in severe sepsis: a metaanalysis of individual patient data from randomized trials. Am J Respir Crit Care Med 2016;15;194(6):681–91. doi: 10.1164/rccm.201601-0024OC.
  28. Vardakas K.Z., Voulgaris G.L., Maliaros A. et al. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomized trials. Lancet Infect Dis 2018;18(1):108–20. doi: 10.1016/S1473-3099(17)30615-1.
  29. Bulik C.C., Nicolau D.P. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011;55(6):3002–4. doi: 10.1128/AAC.01420-10.
  30. De Pascale G., Martucci G., Montini L. et al. Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case-control study. Crit Care 2017;21(1):173. doi: 10.1186/s13054-017-1769-z.
  31. Oliva A., Scorzolini L., Castaldi D. et al. Double-carbapenem regimen, alone or in combination with colistin, in the treatment of infections caused by carbapenemresistant Klebsiella pneumoniae (CR-Kp). J Infect 2017;74(1):103–6. doi: 10.1016/j.jinf.2016.10.002.
  32. Monaco M., Giani T., Raffone M. et al. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Euro Surveill 2014;23;19(42):20939. doi: 10.2807/1560-7917.es2014.19.42.20939.
  33. Falagas M.E., Bliziotis I.A., Tam V.H. Intraventricular or intrathecal use of polymyxins in patients with gramnegative meningitis: a systematic review of the available evidence. Int J Antimicrob Agents 2007;29(1):9–25. doi: 10.1016/j.ijantimicag.2006.08.024.
  34. Nation R.L., Garonzik S.M., Thamlikitkul V. et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis 2017;1;64(5):565–71. doi: 10.1093/cid/ciw839.
  35. Eliseev E.V., Azizov I.S., Zubareva N.A. Review of the international consensus guidelines for the optimal use of the polymyxins. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2019;21(4):282–309. (In Russ.). doi: 10.36488/cmac.2019.4.282-309. [
  36. Falagas M.E., Giannopoulou K.P., Kokolakis G.N., Rafailidis P.I. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 2008;46:1069–77. doi: 10.1086/527442.
  37. Samonis G., Maraki S., Karageorgopoulos D.E. et al. Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis 2012;31:695–701. doi: 10.1007/s10096-011-1360-5.
  38. Parker S., Lipman J., Koulenti D. et al. What is the relevance of fosfomycin pharmacokinetics in the treatment of serious infections in critically ill patients? A systematic review. Int J Antimicrob Agents 2013;42:289–93. doi: 10.1016/j.ijantimicag.2013.05.018.
  39. Le J., McKee B., Srisupha-Olarn W., Burgess D.S. In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae. J Clin Med Res 2011;3:106–10. doi: 10.4021/jocmr551w.
  40. Tanaseanu C., Milutinovic S., Calistru P.I. et al. Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia. BMC Pulm Med 2009;9;9:44. doi: 10.1186/1471-2466-9-44.
  41. Ramirez J., Dartois N., Gandjini H. et al. Randomized phase 2 trial to evaluate the clinical efficacy of two high-¬dosage tigecycline regimens versus imipenemcilastatin for treatment of hospitalacquired pneumonia. Antimicrob Agents Chemother 2013;57:1756–62. doi: 10.1128/AAC.01232-12.
  42. De Pascale G., Montini L., Pennisi M. et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care 2014;5;18(3):R90. doi: 10.1186/cc13858.
  43. Moreno B.B., Simón I.F., García V.P. et al. Tigecycline therapy for infections due to carbapenemase-producing Klebsiella pneumoniae in critically ill patients. Scand J Infect Dis 2014;46(3):175–80. doi: 10.3109/00365548.2013.861608.
  44. Sbrana, F., Malacarne, P., Viaggi, B. et al. Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit. Clin Infect Dis 2013;56(5):697–700. doi: 10.1093/cid/cis969.
  45. Di Carlo P., Gulotta G., Casuccio A. et al. KPC-3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiol 2013;3;13(1):13. doi: 10.1186/1471-2253-13-13.
  46. Geng T.T., Xu X., Huang M. High-dose tigecycline for the treatment of nosocomial carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a retrospective cohort study. Medicine (Baltimore) 2018;97(8):e9961. doi: 10.1097/MD.0000000000009961.
  47. Ni W., Han Y., Liu J. et al. Tigecycline treatment for carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95(11):e3126. doi: 10.1097/MD.0000000000003126.
  48. Kozlov R.S., Stetsyuk O.U., Andreeva I.V. Ceftazidime-avibactam: new rules for the game against multidrug-resistant gram-negative bacteria. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2018;20(1):24–34. (In Russ.). doi: 10.36488/cmac.2018.1.24-34.
  49. Karlowsky J.A., Kazmierczak K.M., Bouchillon S.K. et al. In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa collected in Latin American countries: results from the INFORM Global Surveillance Program, 2012 to 2015. Antimicrob Agents Chemother 2019;27;63(4):e01814–8. doi: 10.1128/AAC.01814-18.
  50. De Jonge B.L.M., Karlowsky J.A., Kazmierczak K.M. et al. In vitro susceptibility to ceftazidime-avibactam of carbapenem-nonsusceptible Enterobacteriaceae isolates collected during the INFORM global surveillance study (2012 to 2014). Antimicrob Agents Chemother 2016;22;60(5):3163–9. doi: 10.1128/AAC.03042-15.
  51. Castón J.J., Lacort-Peralta I., MartínDávila P. et al. Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. Int J Infect Dis 2017;59:118–23. doi: 10.1016/j.ijid.2017.03.021.
  52. Tumbarello M., Trecarichi E.M., Corona A. et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Infect Dis 2019;68(3):355–64. doi: 10.1093/cid/ciy492.
  53. Guimarãesa T., Nouérb S., Martinsc R. et al. Ceftazidime-avibactam as salvage therapy for infections caused by Enterobacteriales co-resistant to carbapenems and polymyxins. Antimicrob. Antimicrob Agents Chemother 2019;23;63(10):e00528–19. doi: 10.1128/AAC.00528-19.
  54. van Duin D., Lok J.J., Earley M. et al. Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis 2018;6;66(2):163–71. doi: 10.1093/cid/cix783.
  55. De la Calle C., Rodríguez O., Morata L. et al. Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidimeavibactam. Int J Antimicrob Agents 2019;53(4):520–4. doi: 10.1016/j.ijantimicag.2018.11.015.
  56. Sousa A., Pérez-Rodríguez T., Soto A. et al. Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother 2018;73:3170–5. doi: 10.1093/jac/dky295.
  57. Wenzler E., Deraedt M.F., Harrington A.T., Danizger L.H. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamaseproducing gram-negative pathogens. Diagn Microbiol Infect Dis 2017;88(4):352–4. doi: 10.1016/j.diagmicrobio.2017.05.009.
  58. Shaw E., Rombauts A., Tubau F. et al. Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M15-producing Klebsiella pneumoniae infection. J Antimicrob Chemother 2018;1;73(4):1104–6. doi: 10.1093/jac/dkx496.
  59. Falcone M., Daikos G.L., Tiseo G. et al. Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by MBL-producing Enterobacterales. Clin Infect Dis 2020; 19;ciaa586. doi: 10.1093/cid/ciaa586.
  60. Micozzi A., Gentile G., Minotti C. et al. Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias. BMC Infect Dis 2017;17(1):203. doi: 10.1186/s12879-017-2297-9.
  61. Girmenia C., Bertaina A., Piciocchi A. et al. Incidence, risk Factors and outcome of pre-engraftment gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: An Italian prospective multicenter survey. Clin Infect Dis 2017;13;65(11):1884–96. doi: 10.1093/cid/cix690.
  62. Forcina A., Baldan R., Marasco V. et al. Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation. Bone Marrow Transplant 2017;52(1):114–9. doi: 10.1038/bmt.2016.234.
  63. Viale P., Tumietto F., Giannella M. et al. Impact of a hospital-wide multifaceted programme for reducing carbapenemresistant Enterobacteriaceae infections in a large teaching hospital in northern Italy. Clin Microbiol Infect 2015;21:242–7. doi: 10.1016/j.cmi.2014.10.020.

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