Severe infections caused by difficult-to-treat Gram-negative bacteria.

Silvia Dettori, Federica Portunato, Antonio Vena, Daniele Roberto Giacobbe, Matteo Bassetti
Author Information
  1. Silvia Dettori: Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neuroscience.
  2. Federica Portunato: Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neuroscience.
  3. Antonio Vena: Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neuroscience.
  4. Daniele Roberto Giacobbe: Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neuroscience.
  5. Matteo Bassetti: Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neuroscience.

Abstract

PURPOSE OF REVIEW: Antimicrobial resistance (AMR) in Gram-negative bacteria (GNB) poses a significant global health concern, contributing to increased infections, mortality rates, and healthcare costs. This review discusses the main clinical manifestations, therapeutic options, and recent findings in managing antibiotic-resistant GNB, with a focus on difficult-to-treat infections.
RECENT FINDINGS: Difficult-to-treat resistance (DTR) is a novel classification that identifies GNB exhibiting intermediate or resistant phenotypes to first-line agents in the carbapenem, beta-lactam, and fluoroquinolone categories. The main pathogens implicated in severe infections include DTR Enterobacterales, DTR Pseudomonas aeruginosa , and DTR Acinetobacter baumannii. Although the clinical implications of DTR strains are still under investigation, certain studies have linked them to prolonged hospital stays and poor patient outcomes.
SUMMARY: Severe infections caused by DTR-GNB pose a formidable challenge for healthcare providers and represent a growing global health issue. The proper administration and optimization of novel antibiotics at our disposal are of paramount importance for combating bacterial resistance and improving patient prognosis.

References

  1. Int J Antimicrob Agents. 2022 Aug;60(2):106611 [PMID: 35697179]
  2. Crit Care. 2020 Jan 30;24(1):29 [PMID: 32000834]
  3. Microbiol Spectr. 2022 Oct 26;10(5):e0292722 [PMID: 36043877]
  4. Intensive Care Med. 2019 Dec;45(12):1703-1717 [PMID: 31664501]
  5. JAC Antimicrob Resist. 2020 Aug 25;2(3):dlaa060 [PMID: 34223017]
  6. Open Forum Infect Dis. 2021 Dec 09;8(12):ofab554 [PMID: 34901302]
  7. Intensive Care Med. 2023 Feb;49(2):178-190 [PMID: 36764959]
  8. Infection. 2018 Aug;46(4):461-468 [PMID: 29594953]
  9. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523 [PMID: 29912399]
  10. Open Forum Infect Dis. 2021 Mar 20;8(6):ofab141 [PMID: 34189161]
  11. Expert Rev Anti Infect Ther. 2017 Jan;15(1):55-65 [PMID: 27766913]
  12. FEMS Microbiol Lett. 2006 May;258(1):72-7 [PMID: 16630258]
  13. Intensive Care Med. 2020 Feb;46(2):163-172 [PMID: 31701205]
  14. JAMA Surg. 2017 Mar 1;152(3):224-232 [PMID: 27851857]
  15. Lancet Infect Dis. 2021 Feb;21(2):226-240 [PMID: 33058795]
  16. Lancet. 2022 Feb 12;399(10325):629-655 [PMID: 35065702]
  17. Microbiol Spectr. 2022 Jun 29;10(3):e0229221 [PMID: 35475683]
  18. Indian J Crit Care Med. 2018 May;22(5):357-360 [PMID: 29910547]
  19. Clin Microbiol Rev. 2007 Jul;20(3):440-58, table of contents [PMID: 17630334]
  20. J Crit Care. 2019 Aug;52:258-264 [PMID: 31054787]
  21. Minerva Anestesiol. 2015 Apr;81(4):405-18 [PMID: 25220548]
  22. Clin Infect Dis. 2020 Oct 23;71(7):1799-1801 [PMID: 31904819]
  23. Open Forum Infect Dis. 2018 Oct 31;5(11):ofy280 [PMID: 30488041]
  24. Crit Care. 2014 May 02;18(3):R87 [PMID: 24886954]
  25. Antimicrob Agents Chemother. 2020 Jan 27;64(2): [PMID: 31740559]
  26. Clin Infect Dis. 2022 Aug 25;75(2):187-212 [PMID: 35439291]
  27. Antibiotics (Basel). 2022 Dec 02;11(12): [PMID: 36551398]
  28. Clin Infect Dis. 2021 Dec 6;73(11):e4521-e4530 [PMID: 32990319]
  29. Clin Microbiol Infect. 2022 Apr;28(4):521-547 [PMID: 34923128]
  30. Crit Care Med. 2015 Aug;43(8):1580-6 [PMID: 25855900]
  31. Biomedicines. 2022 Dec 16;10(12): [PMID: 36552024]
  32. Int J Antimicrob Agents. 2020 Dec;56(6):106184 [PMID: 33045353]
  33. Front Cell Infect Microbiol. 2022 Dec 05;12:1048633 [PMID: 36544909]
  34. Clin Microbiol Infect. 2012 Mar;18(3):268-81 [PMID: 21793988]
  35. Crit Care. 2020 Jun 29;24(1):383 [PMID: 32600375]
  36. Clin Microbiol Rev. 2014 Oct;27(4):647-64 [PMID: 25278570]
  37. Clin Infect Dis. 2020 Apr 15;70(9):1799-1808 [PMID: 31400759]
  38. Crit Care Clin. 2013 Jul;29(3):699-715 [PMID: 23830659]
  39. Clin Infect Dis. 2019 Jan 18;68(3):355-364 [PMID: 29893802]
  40. Infect Dis Ther. 2020 Dec;9(4):769-784 [PMID: 33025557]
  41. J Infect Dis. 2019 Apr 19;219(10):1536-1544 [PMID: 30649434]
  42. Clin Infect Dis. 2020 Mar 3;70(6):1068-1074 [PMID: 31321410]
  43. Clin Infect Dis. 2019 Aug 30;69(6):921-929 [PMID: 30561562]
  44. Antimicrob Resist Infect Control. 2019 Dec 3;8:198 [PMID: 31827779]
  45. Biomed Res Int. 2014;2014:305784 [PMID: 24955354]
  46. Clin Infect Dis. 2022 Sep 29;75(6):1085-1087 [PMID: 35136982]
  47. Pharmacotherapy. 2019 Jan;39(1):10-39 [PMID: 30710469]
  48. Intensive Care Med. 2017 Nov;43(11):1602-1612 [PMID: 28466151]
  49. Crit Care Med. 2017 Jan;45(1):11-19 [PMID: 27611975]
  50. Antimicrob Agents Chemother. 2022 May 17;66(5):e0214221 [PMID: 35311522]
  51. Intensive Care Med. 2020 Feb;46(2):266-284 [PMID: 32047941]
  52. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0201121 [PMID: 34871093]
  53. Antimicrob Agents Chemother. 2020 Apr 21;64(5): [PMID: 32094128]
  54. Clin Infect Dis. 2018 Jan 6;66(2):163-171 [PMID: 29020404]
  55. Rev Soc Bras Med Trop. 2020 Nov 06;53:e20200248 [PMID: 33174956]
  56. J Glob Antimicrob Resist. 2020 Dec;23:292-296 [PMID: 33065329]
  57. Antimicrob Agents Chemother. 2017 Aug 24;61(9): [PMID: 28630191]
  58. J Hosp Infect. 2022 Jan;119:22-32 [PMID: 34627933]
  59. Pan Afr Med J. 2014 Oct 21;19:177 [PMID: 25815098]
  60. JAC Antimicrob Resist. 2021 Dec 11;3(4):dlab188 [PMID: 34909691]
  61. Clin Infect Dis. 2009 Jul 1;49(1):1-45 [PMID: 19489710]
  62. J Med Microbiol. 2020 Feb;69(2):207-217 [PMID: 31976856]
  63. Infez Med. 2019 Mar 1;27(1):11-16 [PMID: 30882373]
  64. Diagn Microbiol Infect Dis. 2022 Jun;103(2):115674 [PMID: 35398608]
  65. Expert Opin Drug Saf. 2022 Apr;21(4):487-498 [PMID: 34632905]
  66. Sci Rep. 2021 Aug 13;11(1):16497 [PMID: 34389761]
  67. Eur J Clin Microbiol Infect Dis. 2012 Apr;31(4):557-66 [PMID: 21796346]
  68. Clin Infect Dis. 2017 Jul 1;65(1):158-161 [PMID: 28329350]
  69. Clin Infect Dis. 2022 Sep 29;75(6):1081-1084 [PMID: 35148378]
  70. Int J Infect Dis. 2017 Jun;59:118-123 [PMID: 28392315]
  71. Diagn Microbiol Infect Dis. 2022 Jan;102(1):115568 [PMID: 34749296]
  72. Clin Infect Dis. 2018 Nov 28;67(12):1803-1814 [PMID: 30052813]
  73. Clin Infect Dis. 2020 Dec 3;71(9):e487-e496 [PMID: 31994704]
  74. JAC Antimicrob Resist. 2021 Nov 17;3(4):dlab174 [PMID: 34806011]
  75. BMC Infect Dis. 2014 Jul 29;14:420 [PMID: 25074742]
  76. J Glob Antimicrob Resist. 2018 Jun;13:165-170 [PMID: 29366723]
  77. Int J Antimicrob Agents. 2019 Apr;53(4):408-415 [PMID: 30415002]
  78. Infect Dis Ther. 2018 Dec;7(4):439-455 [PMID: 30270406]
  79. BMC Infect Dis. 2020 Apr 21;20(1):296 [PMID: 32316926]
  80. J Antimicrob Chemother. 2021 Feb 11;76(3):775-783 [PMID: 33249436]
  81. Antimicrob Agents Chemother. 2017 Jul 25;61(8): [PMID: 28559250]
  82. Eur J Clin Microbiol Infect Dis. 2017 Nov;36(11):1999-2006 [PMID: 27287765]
  83. Int J Antimicrob Agents. 2022 Jul;60(1):106591 [PMID: 35460850]
  84. Am J Infect Control. 2018 Mar;46(3):322-327 [PMID: 29050905]
  85. Int J Antimicrob Agents. 2021 Mar;57(3):106270 [PMID: 33347991]
  86. J Antimicrob Chemother. 2018 Apr 1;73(4):1104-1106 [PMID: 29272413]
  87. Philos Trans R Soc Lond B Biol Sci. 1980 May 16;289(1036):321-31 [PMID: 6109327]
  88. Crit Care. 2015 Mar 02;19:70 [PMID: 25887649]
  89. Front Public Health. 2019 Jun 11;7:151 [PMID: 31245348]
  90. Clin Infect Dis. 2020 Jul 11;71(2):304-310 [PMID: 31545346]
  91. Clin Infect Dis. 2021 Jun 1;72(11):1871-1878 [PMID: 32427286]
  92. Biomed Res Int. 2014;2014:249856 [PMID: 24790993]
  93. Curr Pharm Des. 2013;19(2):209-22 [PMID: 22894618]
  94. Eur Respir J. 2017 Sep 10;50(3): [PMID: 28890434]
  95. Crit Care Med. 2019 Mar;47(3):345-352 [PMID: 30407949]
  96. Microbiol Spectr. 2022 Oct 26;10(5):e0047922 [PMID: 36190427]
  97. Eur J Clin Microbiol Infect Dis. 2021 Aug;40(8):1755-1759 [PMID: 33595756]
  98. Clin Microbiol Rev. 2009 Oct;22(4):582-610 [PMID: 19822890]
  99. Lancet Infect Dis. 2019 Dec;19(12):1299-1311 [PMID: 31563344]
  100. Front Microbiol. 2021 Feb 18;12:614058 [PMID: 33679638]
  101. BMC Infect Dis. 2021 Aug 12;21(1):806 [PMID: 34384380]
  102. JAMA. 2020 Apr 21;323(15):1478-1487 [PMID: 32207816]
  103. Eur J Clin Microbiol Infect Dis. 2021 Mar;40(3):461-475 [PMID: 33009595]

MeSH Term

Humans
Acinetobacter baumannii
Anti-Bacterial Agents
Carbapenems
Gram-Negative Bacteria
Length of Stay

Chemicals

Anti-Bacterial Agents
Carbapenems

Word Cloud

Created with Highcharts 10.0.0infectionsDTRresistanceGNBGram-negativebacteriaglobalhealthhealthcaremainclinicaldifficult-to-treatnovelpatientSeverecausedPURPOSEOFREVIEW:AntimicrobialAMRposessignificantconcerncontributingincreasedmortalityratescostsreviewdiscussesmanifestationstherapeuticoptionsrecentfindingsmanagingantibiotic-resistantfocusRECENTFINDINGS:Difficult-to-treatclassificationidentifiesexhibitingintermediateresistantphenotypesfirst-lineagentscarbapenembeta-lactamfluoroquinolonecategoriespathogensimplicatedsevereincludeEnterobacteralesPseudomonasaeruginosaAcinetobacterbaumanniiAlthoughimplicationsstrainsstillinvestigationcertainstudieslinkedprolongedhospitalstayspooroutcomesSUMMARY:DTR-GNBposeformidablechallengeprovidersrepresentgrowingissueproperadministrationoptimizationantibioticsdisposalparamountimportancecombatingbacterialimprovingprognosis

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