New antimicrobial strategies in cystic fibrosis.

Mireille van Westreenen, Harm A W M Tiddens
Author Information
  1. Mireille van Westreenen: Department of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands. m.vanwestreenen@erasmusmc.nl

Abstract

With more antibiotic resistance and emerging pathogens in cystic fibrosis (CF) patients, the need for new strategies in the lifelong treatment of pulmonary infection has increased. Most of the focus is on chronic infection with Pseudomonas aeruginosa, which is still thought to be the main pathogen leading to advanced CF lung disease. Other bacterial species are also recognized in the pathogenesis of CF lung disease, even though their definitive role is not well established yet. Clearly, expansion of treatment options is urgently needed. This article focuses on recent developments in the field of new antimicrobial strategies for CF. It is clear that studies on new classes of antibiotics or antimicrobial-like drugs are scarce, and that most studies involve new (inhalation) formulations, new routes of delivery, or analogs of existing classes of antibiotics. Studies of new antibiotic-like drugs are, in most cases, in preclinical phases of development and only a few of these agents may reach the market. Importantly, new inhaled antibiotics, e.g. aztreonam, levofloxacin, and fosfomycin, and new, more efficient delivery systems such as dry powder inhalation and liposomes for current antibiotics are in the clinical phase of development. These developments will be of great importance in improving effective treatment and reducing the treatment burden for CF patients in the near future.

References

  1. Pediatr Pulmonol. 2006 Jul;41(7):656-65 [PMID: 16703579]
  2. Diagn Microbiol Infect Dis. 2009 Dec;65(4):431-4 [PMID: 19733029]
  3. J Cyst Fibros. 2008 Sep;7(5):391-7 [PMID: 18358794]
  4. J Immunol. 2003 Jul 15;171(2):931-7 [PMID: 12847264]
  5. Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8 [PMID: 18658109]
  6. Antimicrob Agents Chemother. 1995 Jul;39(7):1467-71 [PMID: 7492087]
  7. J Antimicrob Chemother. 2007 Jun;59(6):1271-9 [PMID: 17403708]
  8. Respir Res. 2002;3:18 [PMID: 11980587]
  9. Respir Med. 2000 Jul;94(7):632-40 [PMID: 10926333]
  10. Curr Opin Immunol. 2001 Feb;13(1):89-95 [PMID: 11154923]
  11. Int J Antimicrob Agents. 2010 Nov;36(5):391-400 [PMID: 20724119]
  12. Antimicrob Agents Chemother. 2009 Sep;53(9):3847-54 [PMID: 19451281]
  13. J Biol Chem. 2008 Nov 21;283(47):32377-85 [PMID: 18799464]
  14. Clin Microbiol Rev. 2008 Jul;21(3):449-65 [PMID: 18625681]
  15. Microbiology (Reading). 2002 Oct;148(Pt 10):3195-3202 [PMID: 12368453]
  16. Pediatr Pulmonol. 2009 Apr;44(4):402-9 [PMID: 19283840]
  17. J Med Microbiol. 1990 Apr;31(4):271-4 [PMID: 2325116]
  18. J Antimicrob Chemother. 2008 Apr;61(4):859-68 [PMID: 18305202]
  19. Semin Respir Crit Care Med. 2009 Feb;30(1):92-101 [PMID: 19199191]
  20. Lancet Infect Dis. 2006 Sep;6(9):589-601 [PMID: 16931410]
  21. Clin Microbiol Infect. 2007 Jun;13(6):560-78 [PMID: 17266725]
  22. Expert Opin Investig Drugs. 2007 Sep;16(9):1441-8 [PMID: 17714029]
  23. Endocr Metab Immune Disord Drug Targets. 2007 Jun;7(2):75-82 [PMID: 17584147]
  24. Cochrane Database Syst Rev. 2009 Oct 07;(4):CD004197 [PMID: 19821321]
  25. Curr Top Microbiol Immunol. 2006;306:153-82 [PMID: 16909921]
  26. J Antimicrob Chemother. 2002 Feb;49(2):403-6 [PMID: 11815589]
  27. J Antimicrob Chemother. 2002 Aug;50(2):265-9 [PMID: 12161410]
  28. J Infect Dis. 2004 Oct 1;190(7):1245-53 [PMID: 15346334]
  29. Am J Clin Pathol. 2007 Jul;128(1):32-4 [PMID: 17580270]
  30. Clin Infect Dis. 2008 May 1;46(9):1401-8 [PMID: 18419443]
  31. Thorax. 1997 Nov;52(11):987-93 [PMID: 9487348]
  32. J Leukoc Biol. 2004 Nov;76(5):909-25 [PMID: 15292276]
  33. Antimicrob Agents Chemother. 2009 Apr;53(4):1434-42 [PMID: 19188393]
  34. Clin Microbiol Infect. 2008 Dec;14 Suppl 6:19-29 [PMID: 19040463]
  35. J Pharmacobiodyn. 1982 Dec;5(12):941-50 [PMID: 7169607]
  36. Clin Infect Dis. 2008 Apr 1;46(7):1069-77 [PMID: 18444827]
  37. J Cyst Fibros. 2009 Jul;8(4):291-3 [PMID: 19411195]
  38. Antimicrob Agents Chemother. 2006 Jun;50(6):1953-8 [PMID: 16723551]
  39. J Antimicrob Chemother. 2007 Nov;60(5):1064-73 [PMID: 17846106]
  40. J Med Microbiol. 2006 Dec;55(Pt 12):1615-1617 [PMID: 17108262]
  41. J Antimicrob Chemother. 2005 Jun;55(6):921-7 [PMID: 15883175]
  42. Am J Respir Cell Mol Biol. 1999 Jan;20(1):69-78 [PMID: 9870919]
  43. Infect Immun. 2000 May;68(5):2748-55 [PMID: 10768969]
  44. Microbiology (Reading). 2009 Sep;155(Pt 9):2826-2837 [PMID: 19477905]
  45. Nature. 2005 Aug 25;436(7054):1171-5 [PMID: 16121184]
  46. Biochem Pharmacol. 2002 Nov 1;64(9):1407-13 [PMID: 12392822]
  47. Antimicrob Agents Chemother. 2006 Sep;50(9):2946-50 [PMID: 16940086]
  48. J Antimicrob Chemother. 2007 Sep;60(3):546-54 [PMID: 17595284]
  49. Pediatr Pulmonol. 2008 Sep;43(9):874-81 [PMID: 18668689]
  50. Infect Immun. 1993 Dec;61(12):5049-55 [PMID: 8225581]
  51. Int J Antimicrob Agents. 2008 Nov;32(5):437-40 [PMID: 18715759]
  52. Appl Environ Microbiol. 2006 Mar;72(3):2005-13 [PMID: 16517649]
  53. Clin Chest Med. 2002 Sep;23(3):655-63 [PMID: 12371001]
  54. Pediatr Pulmonol. 2008 Jan;43(1):47-58 [PMID: 18041081]
  55. J Med Microbiol. 2009 Jun;58(Pt 6):765-773 [PMID: 19429753]
  56. J Antimicrob Chemother. 2004 Dec;54(6):1057-61 [PMID: 15509615]
  57. Am Rev Respir Dis. 1985 Oct;132(4):761-5 [PMID: 3931522]
  58. Expert Rev Respir Med. 2009 Aug;3(4):349-61 [PMID: 20477327]
  59. Antimicrob Agents Chemother. 2003 Mar;47(3):972-8 [PMID: 12604529]
  60. Methods Mol Biol. 2009;480:165-74 [PMID: 19085124]
  61. Antimicrob Agents Chemother. 2005 Jun;49(6):2510-1 [PMID: 15917558]
  62. Mol Microbiol. 1991 Mar;5(3):641-6 [PMID: 2046549]
  63. Antimicrob Agents Chemother. 2009 Sep;53(9):3923-8 [PMID: 19528273]
  64. Ann Pharmacother. 2000 Nov;34(11):1238-42 [PMID: 11098334]
  65. J Cyst Fibros. 2003 Mar;2(1):19-24 [PMID: 15463841]
  66. Int J Antimicrob Agents. 2008 Nov;32(5):461-3 [PMID: 18703318]
  67. Chest. 2009 May;135(5):1223-1232 [PMID: 19420195]
  68. Curr Med Chem. 2009;16(5):564-75 [PMID: 19199922]
  69. Hum Genomics. 2009 Apr;3(3):246-56 [PMID: 19403459]
  70. Crit Rev Biotechnol. 1990;10(3):223-40 [PMID: 1702690]
  71. Pediatr Pulmonol. 2007 Apr;42(4):307-13 [PMID: 17352404]
  72. PLoS One. 2008 Aug 06;3(8):e2908 [PMID: 18682840]
  73. Antimicrob Agents Chemother. 2009 Apr;53(4):1443-9 [PMID: 19188397]
  74. AAPS J. 2008 Jun;10(2):254-60 [PMID: 18454321]
  75. Pediatr Pulmonol. 2000 Mar;29(3):210-2 [PMID: 10686042]
  76. J Pharm Sci. 2008 Aug;97(8):3356-66 [PMID: 17990305]
  77. Antimicrob Agents Chemother. 2009 Apr;53(4):1690-2 [PMID: 19139284]
  78. J Antimicrob Chemother. 2007 Oct;60(4):760-9 [PMID: 17673475]
  79. Antimicrob Agents Chemother. 1996 Mar;40(3):665-9 [PMID: 8851590]
  80. ORL J Otorhinolaryngol Relat Spec. 1985;47(1):42-8 [PMID: 3969267]
  81. Int J Antimicrob Agents. 2001 Feb;17(2):93-6 [PMID: 11165111]
  82. Eur Respir J. 1998 Sep;12(3):592-4 [PMID: 9762785]
  83. Ann Med. 2007;39(3):162-76 [PMID: 17457715]
  84. Antimicrob Agents Chemother. 2006 Feb;50(2):819-21 [PMID: 16436756]
  85. J Aerosol Med. 2004 Summer;17(2):153-6 [PMID: 15294065]
  86. Int J Antimicrob Agents. 2010 Feb;35(2):101-6 [PMID: 19939637]
  87. Pediatr Pulmonol. 2007 Sep;42(9):751-6 [PMID: 17647287]
  88. Am J Clin Dermatol. 2008;9(4):245-54 [PMID: 18572975]
  89. J Cyst Fibros. 2007 May;6(3):244-6 [PMID: 17055346]
  90. Microbiol Rev. 1996 Sep;60(3):539-74 [PMID: 8840786]
  91. Lancet. 2005 Aug 6-12;366(9484):463-71 [PMID: 16084254]
  92. J Bacteriol. 2007 May;189(9):3639-44 [PMID: 17337576]
  93. Nature. 2002 Apr 18;416(6882):740-3 [PMID: 11961556]
  94. Pediatr Pulmonol. 2008 Aug;43(8):753-9 [PMID: 18613006]
  95. J Antimicrob Chemother. 2008 Nov;62(5):889-94 [PMID: 18662945]
  96. Clin Microbiol Rev. 2010 Apr;23(2):299-323 [PMID: 20375354]
  97. FEBS Lett. 1999 Jun 11;452(3):309-13 [PMID: 10386612]
  98. Adv Pediatr Infect Dis. 1997;13:349-76 [PMID: 9544319]
  99. Int J Antimicrob Agents. 2009 Oct;34(4):370-4 [PMID: 19505804]
  100. Curr Drug Deliv. 2008 Apr;5(2):114-9 [PMID: 18393813]
  101. J Clin Invest. 1999 Apr;103(8):1113-7 [PMID: 10207162]
  102. Am J Respir Crit Care Med. 2008 May 1;177(9):995-1001 [PMID: 18263800]
  103. J Antimicrob Chemother. 2009 Oct;64(4):829-36 [PMID: 19679597]
  104. Cell. 1996 Apr 19;85(2):229-36 [PMID: 8612275]
  105. J Antimicrob Chemother. 2008 Dec;62(6):1291-7 [PMID: 18931388]
  106. J Aerosol Med. 2006 Winter;19(4):456-65 [PMID: 17196074]
  107. Microbiology (Reading). 2007 Apr;153(Pt 4):917-923 [PMID: 17379702]
  108. J Antimicrob Chemother. 2003 Aug;52(2):247-52 [PMID: 12837733]
  109. Antimicrob Agents Chemother. 2008 Feb;52(2):483-90 [PMID: 18025118]
  110. J Cyst Fibros. 2007 Jul;6(4):284-92 [PMID: 17185047]
  111. Recent Pat Antiinfect Drug Discov. 2006 Jun;1(2):157-75 [PMID: 18221142]
  112. Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S25-34 [PMID: 16323116]
  113. Crit Care. 2010;14(3):R84 [PMID: 20459721]

MeSH Term

Administration, Inhalation
Anti-Bacterial Agents
Bacterial Infections
Cystic Fibrosis
Drug Resistance, Microbial
Humans
Infusions, Parenteral
Respiratory Tract Infections
Treatment Outcome

Chemicals

Anti-Bacterial Agents

Word Cloud

Created with Highcharts 10.0.0newCFtreatmentantibioticsstrategiescysticfibrosispatientsinfectionlungdiseasedevelopmentsantimicrobialstudiesclassesdrugsinhalationdeliverydevelopmentantibioticresistanceemergingpathogensneedlifelongpulmonaryincreasedfocuschronicPseudomonasaeruginosastillthoughtmainpathogenleadingadvancedbacterialspeciesalsorecognizedpathogenesiseventhoughdefinitiverolewellestablishedyetClearlyexpansionoptionsurgentlyneededarticlefocusesrecentfieldclearantimicrobial-likescarceinvolveformulationsroutesanalogsexistingStudiesantibiotic-likecasespreclinicalphasesagentsmayreachmarketImportantlyinhaledegaztreonamlevofloxacinfosfomycinefficientsystemsdrypowderliposomescurrentclinicalphasewillgreatimportanceimprovingeffectivereducingburdennearfutureNew

Similar Articles

Cited By