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New Antimicrobial Strategies in Cystic Fibrosis

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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.

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References

  1. Harrison F. Microbial ecology of the cystic fibrosis lung. Microbiology 2007 Apr; 153 (Pt 4): 917–23

    Article  PubMed  CAS  Google Scholar 

  2. Ratjen F. Changes in strategies for optimal antibacterial therapy in cystic fibrosis. Int J Antimicrob Agents 2001; 17(2): 93–6

    Article  PubMed  CAS  Google Scholar 

  3. Sabra W, Kim EJ, Zeng AP. Physiological responses of Pseudomonas aeruginosa PAO1 to oxidative stress in controlled microaerobic and aerobic cultures. Microbiology 2002; 148: 3195–202

    PubMed  CAS  Google Scholar 

  4. Govan JR, Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 1996; 60(3): 539–74

    PubMed  CAS  Google Scholar 

  5. Pritt B, O’Brien L, Winn W. Mucoid pseudomonas in cystic fibrosis. Am J Clin Pathol 2007; 128(1): 32–4

    Article  PubMed  Google Scholar 

  6. O’May CY, Sanderson K, Roddam LF, et al. Iron-binding compounds impair Pseudomonas aeruginosa biofilm formation, especially under anaerobic conditions. J Med Microbiol 2009; 58 (Pt 6): 765–73

    Article  PubMed  CAS  Google Scholar 

  7. Tré-Hardy M, Traore H, El Manssouri N, et al. Evaluation of long-term coadministration of tobramycin and clarithromycin in a mature biofilm model of cystic fibrosis clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents 2009; 34(4): 370–4

    Article  PubMed  CAS  Google Scholar 

  8. Treggiari MM, Rosenfeld M, Retsch-Bogart G, et al. Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr Pulmonol 2007; 42(9): 751–6

    Article  PubMed  Google Scholar 

  9. Conway SP, Lee TWR. Prevention of chronic Pseudomonas aeruginosa infection in people with cystic fibrosis. Exp Rev Resp Med 2009; 3: 349–61

    Article  Google Scholar 

  10. Lipuma JJ. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 2010; 23(2): 299–323

    Article  PubMed  Google Scholar 

  11. Doud M, Zeng E, Schneper L, et al. Approaches to analyse dynamic microbial communities such as those seen in cystic fibrosis lung. Hum Genomics 2009; 3(3): 246–56

    Article  PubMed  CAS  Google Scholar 

  12. Bittar F, Richet H, Dubus JC, et al. Molecular detection of multiple emerging pathogens in sputa from cystic fibrosis patients. PLoS One 2008; 6; 3 (8): e2908

    Article  CAS  Google Scholar 

  13. Tunney MM, Field TR, Moriarty TF, et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 2008; 177(9): 995–1001

    Article  PubMed  Google Scholar 

  14. Jewes LA, Spencer RC. The incidence of anaerobes in the sputum of patients with cystic fibrosis. J Med Microbiol 1990; 31(4): 271–4

    Article  PubMed  CAS  Google Scholar 

  15. Ebert DL, Olivier KN. Nontuberculous mycobacteria in the setting of cystic fibrosis. Clin Chest Med 2002; 23(3): 655–63

    Article  PubMed  Google Scholar 

  16. Aaron SD, Vandemheen KL, Ferris W, et al. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet 2005; 366(9484): 463–71

    Article  PubMed  CAS  Google Scholar 

  17. Foweraker JE, Laughton CR, Brown DF. Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing. J Antimicrob Chemother 2005; 55(6): 921–7

    Article  PubMed  CAS  Google Scholar 

  18. Laube DM, Yim S, Ryan LK, et al. Antimicrobialpeptides in the airway. Curr Top Microbiol Immunol 2006; 306: 153–82

    Article  PubMed  CAS  Google Scholar 

  19. Harder J, Gläser R, Schröder JM. The role and potential therapeutical applications of antimicrobial proteins in infectious and inflammatory diseases. Endocr Metab Immune Disord Drug Targets 2007; 7(2): 75–82

    Article  PubMed  CAS  Google Scholar 

  20. Sagel SD, Sontag MK, Accurso FJ. Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis. Pediatr Pulmonol 2009; 44(4): 402–9

    Article  PubMed  Google Scholar 

  21. Smith JJ, Travis SM, Greenberg EP, et al. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 1996; 85(2): 229–36

    Article  PubMed  CAS  Google Scholar 

  22. Travis SM, Singh PK, Welsh MJ. Antimicrobial peptides and proteins in the innate defense of the airway surface. Curr Opin Immunol 2001; 13(1): 89–95

    Article  PubMed  CAS  Google Scholar 

  23. Travis SM, Anderson NN, Forsyth WR, et al. Bactericidal activity of mammalian cathelicidin-derived peptides. Infect Immun 2000; 68(5): 2748–55

    Article  PubMed  CAS  Google Scholar 

  24. Caraher EM, Gumulapurapu K, Taggart CC, et al. The effect of recombinant human lactoferrin on growth and the antibiotic susceptibility of the cystic fibrosis pathogen Burkholderia cepacia complex when cultured planktonically or as biofilms. J Antimicrob Chemother 2007; 60(3): 546–54

    Article  PubMed  CAS  Google Scholar 

  25. Britigan BE, Hayek MB, Doebbeling BN, et al. Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. Infect Immun 1993; 61(12): 5049–55

    PubMed  CAS  Google Scholar 

  26. Taggart CC, Greene CM, Smith SG, et al. Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 2003; 171(2): 931–7

    PubMed  CAS  Google Scholar 

  27. Rogan MP, Taggart CC, Greene CM. Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis. J Infect Dis 2004; 190: 1245–53

    Article  PubMed  CAS  Google Scholar 

  28. Bals R, Weiner DJ, Meegalla RL, et al. Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. J Clin Invest 1999; 103(8): 1113–7

    Article  PubMed  CAS  Google Scholar 

  29. Levy O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J Leukoc Biol 2004; 76(5): 909–25

    Article  PubMed  CAS  Google Scholar 

  30. Simpson AJ, Maxwell AI, Govan JR, et al. Elafin (elastase-specific inhibitor) has anti-microbial activity against gram-positive and gram-negative respiratory pathogens. FEBS Lett 1999; 452(3): 309–13

    Article  PubMed  CAS  Google Scholar 

  31. Guyot N, Butler MW, McNally P, et al. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis. J Biol Chem 2008; 283(47): 32377–85

    Article  PubMed  CAS  Google Scholar 

  32. Bellemare A, Vernoux N, Morisset D, et al. Human pre-elafin inhibits a Pseudomonas aeruginosa-secreted peptidase and prevents its proliferation in complex media. Antimicrob Agents Chemother 2008; 52(2): 483–90

    Article  PubMed  CAS  Google Scholar 

  33. Rees DD, Rogers RA, Cooley J, et al. Recombinant human monocyte/neutrophil elastase inhibitor protects rat lungs against injury from cystic fibrosis airway secretions. Am J Respir Cell Mol Biol 1999; 20(1): 69–78

    PubMed  CAS  Google Scholar 

  34. Albrecht MT, Wang W, Shamova O, et al. Binding of protegrin-1 to Pseudomonas aeruginosa and Burkholderia cepacia. Respir Res 2002; 3: 18

    Article  PubMed  Google Scholar 

  35. Kristiansen JE, Hendricks O, Delvin T, et al. Reversal of resistance in microorganisms by help of non-antibiotics. J Antimicrob Chemother 2007; 59(6): 1271–9

    Article  PubMed  CAS  Google Scholar 

  36. Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med 2007; 39(3): 162–76

    Article  PubMed  CAS  Google Scholar 

  37. Mesaros N, Nordmann P, Plésiat P, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect 2007; 13(6): 560–78

    Article  PubMed  CAS  Google Scholar 

  38. Van Bambeke F, Pages J, Lee VJ. Inhibitors of bacterial efflux pumps as adjuvants in antibiotic treatments and diagnostic tools for detection of resistance by efflux. Rec Patents Antiinfect Drug Discov 2006; 1: 157–75

    Article  Google Scholar 

  39. Nakano MM, Zuber P. Molecular biology of antibiotic production in Bacillus. Crit Rev Biotechnol 1990; 10(3): 223–40

    Article  PubMed  CAS  Google Scholar 

  40. Cox AD, Wilkinson SG. Ionizing groups in lipopolysaccharides of Pseudomonas cepacia in relation to antibiotic resistance. Mol Microbiol 1991; 5: 641–6

    Article  PubMed  CAS  Google Scholar 

  41. Littlewood JM, Koch C, Lambert PA, et al. A ten year review of colomycin. Respir Med 2000; 94(7): 632–40

    Article  PubMed  CAS  Google Scholar 

  42. Conway SP, Etherington C, Munday J, et al. Safety and tolerability of bolus intravenous colistin in acute respiratory exacerbations in adults with cystic fibrosis. Ann Pharmacother 2000; 34(11): 1238–42

    Article  PubMed  CAS  Google Scholar 

  43. Conway SP, Pond MN, Watson A, et al. Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis. Thorax 1997; 52(11): 987–93

    Article  PubMed  CAS  Google Scholar 

  44. Johansen HK, Moskowitz SM, Ciofu O, et al. Spread of colistin resistant nonmucoid Pseudomonas aeruginosa among chronically infected Danish cystic fibrosis patients. J Cyst Fibros 2008; 7(5): 391–7

    Article  PubMed  Google Scholar 

  45. Cummins J, Reen FJ, Baysse C, et al. Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa. Microbiology 2009; 155 (Pt 9): 2826–37

    Article  PubMed  CAS  Google Scholar 

  46. Coly-Mycin M parenteral [package insert]. Bristol (TN): Monarch Pharmaceuticals, Inc., 2006

    Google Scholar 

  47. Bergen PJ, Li J, Rayner CR, et al. Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa. Antimicrob Agents Chemother 2006; 50(6): 1953–8

    Article  PubMed  CAS  Google Scholar 

  48. Hogardt M, Schmoldt S, Götzfried M, et al. Pitfalls of polymyxin antimicrobial susceptibility testing of Pseudomonas aeruginosa isolated from cystic fibrosis patients. J Antimicrob Chemother 2004; 54(6): 1057–61

    Article  PubMed  CAS  Google Scholar 

  49. Miyajima Y, Hiramatsu K, Mizukami E, et al. In vitro and in vivo potency of polymyxin B against IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa. Int J Antimicrob Agents 2008; 32(5): 437–40

    Article  PubMed  CAS  Google Scholar 

  50. Oliveira MS, Prado GV, Costa SF, et al. Polymyxin B and colistimethate are comparable as to efficacy and renal toxicity. Diagn Microbiol Infect Dis 2009; 65(4): 431–4

    Article  PubMed  CAS  Google Scholar 

  51. Li J, Rayner CR, Nation RL, et al. Hetero-resistance to colistin in multidrugresistant Acinetobacter baumannii. Antimicrob Agents Chemother 2006; 50(9): 2946–50

    Article  PubMed  CAS  Google Scholar 

  52. Li J, Nation RL, Turnidge JD, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 2006; 6(9): 589–601

    Article  PubMed  CAS  Google Scholar 

  53. Landman D, Georgescu C, Martin DA, et al. Polymyxins revisited. Clin Microbiol Rev 2008; 21(3): 449–65

    Article  PubMed  CAS  Google Scholar 

  54. Ledson MJ, Gallagher MJ, Cowperthwaite C, et al. Four years’ experience of intravenous colomycin in an adult cystic fibrosis unit. Eur Respir J 1998; 12: 592–4

    Article  PubMed  CAS  Google Scholar 

  55. Fosfomycin® for injection [product information]. Last updated August 1999. New York: Sanofi-Synthelabo, 1999

  56. Faruqi S, McCreanor J, Moon T, et al. Fosfomycin for Pseudomonas-related exacerbations of cystic fibrosis. Int J Antimicrob Agents 2008; 32(5): 461–3

    Article  PubMed  CAS  Google Scholar 

  57. Falagas ME, Giannopoulou KP, Kokolakis GN, et al. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 2008; 46(7): 1069–77

    Article  PubMed  Google Scholar 

  58. Schülin T. In vitro activity of the aerosolized agents colistin and tobramycin and five intravenous agents against Pseudomonas aeruginosa isolated from cystic fibrosis patients in southwestern Germany. J Antimicrob Chemother 2002 Feb; 49(2): 403–6

    Article  PubMed  Google Scholar 

  59. Mirakhur A, Gallagher MJ, Ledson MJ, et al. Fosfomycin therapy for multi-resistant Pseudomonas aeruginosa in cystic fibrosis. J Cyst Fibros 2003; 2(1): 19–24

    Article  PubMed  CAS  Google Scholar 

  60. Inouye S, Niizato T, Komiya I, et al. Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats. J Pharmacobiodyn 1982; 5(12): 941–50

    Article  PubMed  CAS  Google Scholar 

  61. Ohtani I, Ohtsuki K, Aikawa T, et al. Protective effect of fosfomycin against aminoglycoside ototoxicity. ORL J Otorhinolaryngol Relat Spec 1985; 47(1): 42–8

    Article  PubMed  CAS  Google Scholar 

  62. Cree M, Stacey S, Graham N, et al. Fosfomycin: investigation of a possible new route of administration of an old drug: a case study. J Cyst Fibros 2007; 6(3): 244–6

    Article  PubMed  CAS  Google Scholar 

  63. Kurlandsky LE, Fader RC. In vitro activity of minocycline against respiratory pathogens from patients with cystic fibrosis. Pediatr Pulmonol 2000; 29(3): 210–2

    Article  PubMed  CAS  Google Scholar 

  64. Nzula S, Vandamme P, Govan JR. Influence of taxonomic status on the in vitro antimicrobial susceptibility of the Burkholderia cepacia complex. J Antimicrob Chemother 2002; 50(2): 265–9

    Article  PubMed  CAS  Google Scholar 

  65. Grimwood K, Kidd TJ, Tweed M. Successful treatment of cepacia syndrome. J Cyst Fibros 2009; 8(4): 291–3

    Article  PubMed  CAS  Google Scholar 

  66. Falagas ME, Valkimadi PE, Huang YT, et al. Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review. J Antimicrob Chemother 2008; 62(5): 889–94

    Article  PubMed  CAS  Google Scholar 

  67. Govan JR. Multidrug-resistant pulmonary infection in cystic fibrosis: what does ‘resistant’ mean? J Med Microbiol 2006; 55 (Pt 12): 1615–7

    Article  PubMed  CAS  Google Scholar 

  68. Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2009; (4): CD004197

    Google Scholar 

  69. Moskowitz SM, Silva SJ, Mayer-Hamblett N, et al. Shifting patterns of inhaled antibiotic use in cystic fibrosis. Pediatr Pulmonol 2008; 43(9): 874–81

    Article  PubMed  Google Scholar 

  70. Schüepp KG, Straub D, Möller A, et al. Deposition of aerosols in infants and children. J Aerosol Med 2004; 17(2): 153–6

    Article  PubMed  CAS  Google Scholar 

  71. Chambless JD, Hunt SM, Stewart PS. A three-dimensional computer model of four hypothetical mechanisms protecting biofilms from antimicrobials. Appl Environ Microbiol 2006; 72(3): 2005–13

    Article  PubMed  CAS  Google Scholar 

  72. Mendelman PM, Smith AL, Levy J, et al. Aminoglycoside penetration, in-activation, and efficacy in cystic fibrosis sputum. Am Rev Respir Dis 1985; 132(4): 761–5

    PubMed  CAS  Google Scholar 

  73. Drenkard E, Ausubel FM. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 2002; 416(6882): 740–3

    Article  PubMed  CAS  Google Scholar 

  74. Hoffman LR, D’Argenio DA, MacCoss MJ, et al. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 2005; 436(7054): 1171–5

    Article  PubMed  CAS  Google Scholar 

  75. Waldrep JC, Dhand R. Advanced nebulizer designs employing vibrating mesh/aperture plate technologies for aerosol generation. Curr Drug Deliv 2008; 5(2): 114–9

    Article  PubMed  CAS  Google Scholar 

  76. Coates AL, Green M, Leung K, et al. Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis: a pilot project. Pediatr Pulmonol 2008; 43(8): 753–9

    Article  PubMed  Google Scholar 

  77. Falagas ME, Michalopoulos A, Metaxas EI. Pulmonary drug delivery systems for antimicrobial agents: facts and myths. Int J Antimicrob Agents 2010; 35(2): 101–6

    Article  PubMed  CAS  Google Scholar 

  78. Gibson RL, Retsch-Bogart GZ, Oermann C, et al. Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatr Pulmonol 2006; 41(7): 656–65

    Article  PubMed  Google Scholar 

  79. Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135(5): 1223–32

    Article  PubMed  CAS  Google Scholar 

  80. McCoy KS, Quittner AL, Oermann CM, et al. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med 2008; 178(9): 921–8

    Article  PubMed  CAS  Google Scholar 

  81. Retsch-Bogart GZ, Burns JL, Otto KL, et al. A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Pulmonol 2008; 43(1): 47–58

    Article  PubMed  Google Scholar 

  82. Sabet M, Miller CE, Nolan TG, et al. Efficacy of aerosol MP-376, a levo-floxacin inhalation solution, in models of mouse lung infection due to Pseudomonas aeruginosa. Antimicrob Agents Chemother 2009; 53(9): 3923–8

    Article  PubMed  CAS  Google Scholar 

  83. MacLeod DL, Barker LM, Sutherland JL, et al. Antibacterial activities of a fosfomycin/tobramycin combination: a novel inhaled antibiotic for bronchiectasis. J Antimicrob Chemother 2009; 64(4): 829–36

    Article  PubMed  CAS  Google Scholar 

  84. Beaulac C, Clément-Major S, Hawari J, et al. Eradication of mucoid Pseudomonas aeruginosa with fluid liposome-encapsulated tobramycin in an animal model of chronic pulmonary infection. J Antimicrob Agents Chemother 1996; 40(3): 665–9

    CAS  Google Scholar 

  85. Marier JF, Brazier JL, Lavigne J, et al. Liposomal tobramycin against pulmonary infections of Pseudomonas aeruginosa: a pharmacokinetic and efficacy study following single and multiple intratracheal administrations in rats. J Antimicrob Chemother 2003; 52(2): 247–52

    Article  PubMed  CAS  Google Scholar 

  86. Meers P, Neville M, Malinin V, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 2008; 61(4): 859–68

    Article  PubMed  CAS  Google Scholar 

  87. Okusanya OO, Bhavnani SM, Hammel J, et al. Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. Antimicrob Agents Chemother 2009; 53(9): 3847–54

    Article  PubMed  CAS  Google Scholar 

  88. de Steenwinkel JE, van Vianen W, Ten Kate MT, et al. Targeted drug delivery to enhance efficacy and shorten treatment duration in disseminated Mycobacterium avium infection in mice. J Antimicrob Chemother 2007; 60(5): 1064–73

    Article  PubMed  CAS  Google Scholar 

  89. Halwani M, Mugabe C, Azghani AO, et al. Bactericidal efficacy of liposomal aminoglycosides against Burkholderia cenocepacia. J Antimicrob Chemother 2007; 60(4): 760–9

    Article  PubMed  CAS  Google Scholar 

  90. Halwani M, Yebio B, Suntres ZE, et al. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. J Antimicrob Chemother 2008; 62(6): 1291–7

    Article  PubMed  CAS  Google Scholar 

  91. Saiman L. Selected Topics in novel methods of antibiotic delivery: aerosolized antibiotics and lipid preparations. Adv Pediatr Infect Dis 1998; 13: 349–76

    Google Scholar 

  92. Omri A, Suntres ZE, Shek PN. Enhanced activity of liposomal polymyxin B against Pseudomonas aeruginosa in a rat model of lung infection. Biochem Pharmacol 2002; 64(9): 1407–13

    Article  PubMed  CAS  Google Scholar 

  93. Rijnders BJ, Cornelissen JJ, Slobbe L, et al. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin Infect Dis 2008; 46(9): 1401–8

    Article  PubMed  CAS  Google Scholar 

  94. Tiddens HA, Geller DE, Challoner P, et al. Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older. J Aerosol Med 2006; 19(4): 456–65

    Article  PubMed  CAS  Google Scholar 

  95. Westerman EM, De Boer AH, Le Brun PP, et al. Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study. J Cyst Fibros 2007; 6(4): 284–92

    Article  PubMed  CAS  Google Scholar 

  96. Kraft KS, Grant M. Preparation of macromolecule-containing dry powders for pulmonary delivery. Methods Mol Biol 2009; 480: 165–74

    Article  PubMed  CAS  Google Scholar 

  97. Tsifansky MD, Yeo Y, Evgenov OV, et al. Microparticles for inhalational delivery of antipseudomonal antibiotics. AAPS J 2008; 10(2): 254–60

    Article  PubMed  CAS  Google Scholar 

  98. Adi H, Young PM, Chan HK, et al. Cospray dried antibiotics for dry powder lung delivery. J Pharm Sci 2008; 97(8): 3356–66

    Article  PubMed  CAS  Google Scholar 

  99. Geller DE, Konstan MW, Smith J, et al. Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol 2007; 42(4): 307–13

    Article  PubMed  Google Scholar 

  100. Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis 2006 Jan 1; 42Suppl. 1: S25–34

    Article  PubMed  CAS  Google Scholar 

  101. Welte T, Pletz MW. Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. Int J Antimicrob Agents. Epub 2010 Aug 17

  102. Neuner EA, Ritchie DJ, Micek ST. New antibiotics for healthcare-associated pneumonia. Semin Respir Crit Care Med 2009; 30(1): 92–101

    Article  PubMed  Google Scholar 

  103. French GL. What’s new and not so new on the antimicrobial horizon? Clin Microbiol Infect 2008; 14Suppl. 6: 19–29

    Article  PubMed  CAS  Google Scholar 

  104. Kohlhoff SA, Sharma R. Iclaprim. Expert Opin Investig Drugs 2007; 16(9): 1441–8

    Article  PubMed  CAS  Google Scholar 

  105. Zhanel GG, Karlowsky JA. In vitro activity of iclaprim against respiratory and bacteremic isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 2009; 53(4): 1690–2

    Article  PubMed  CAS  Google Scholar 

  106. Nguyen HA, Denis O, Vergison A, et al. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains. Antimicrob Agents Chemother 2009; 53(4): 1434–42

    Article  PubMed  CAS  Google Scholar 

  107. Nguyen HA, Denis O, Vergison A, et al. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small colony variant isolated from a cystic fibrosis patient: 2. Study of antibiotic combinations. Antimicrob Agents Chemother 2009; 53(4): 1443–9

    Article  PubMed  CAS  Google Scholar 

  108. Zhanel GG, Lam A, Schweizer F, et al. Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin. Am J Clin Dermatol 2008; 9(4): 245–54

    Article  PubMed  Google Scholar 

  109. Traczewski MM, Brown SD. In vitro activity of doripenem against Pseudomonas aeruginosa and Burkholderia cepacia isolates from both cystic fibrosis and non-cystic fibrosis patients. Antimicrob Agents Chemother 2006; 50(2): 819–21

    Article  PubMed  CAS  Google Scholar 

  110. Bassetti M, Nicolini L, Esposito S, et al. Current status of newer carbapenems. Curr Med Chem 2009; 16(5): 564–75

    Article  PubMed  CAS  Google Scholar 

  111. Chen Y, Garber E, Zhao Q, et al. In vitro activity of doripenem (S-4661) against multidrug-resistant gram-negative bacilli isolated from patients with cystic fibrosis. Antimicrob Agents Chemother 2005; 49(6): 2510–1

    Article  PubMed  CAS  Google Scholar 

  112. Kitamura A, Hoshino K, Kimura Y, et al. Contribution of the C-8 substituent of DU-6859a, a new potent fluoroquinolone, to its activity against DNA gyrase mutants of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1995; 39: 1467–71

    Article  PubMed  CAS  Google Scholar 

  113. Kollef MH, Nathwani D, Merchant S, et al. Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators. Crit Care 2010; 14(3): R84

    Article  PubMed  Google Scholar 

  114. Dean CR, Visalli MA, Projan SJ, et al. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 2003; 47: 972–8

    Article  PubMed  CAS  Google Scholar 

  115. Ortega XP, Cardona ST, Brown AR, et al. A putative gene cluster for aminoarabinose biosynthesis is essential for Burkholderia cenocepacia viability. J Bacteriol 2007; 189(9): 3639–44

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

There was no funding for the preparation of this manuscript. Harm Tiddens received within the last 3 years honoraria and travel expenses for lectures and for participation in expert panels from Novartis, Gilead, and Bayer. The BV Kindergeneeskunde of the Erasmus MC — Sophia Children’s Hospital has in the last 3 years received research grants from Novartis. Mireille van Westreenen has no conflicts of interest directly related to this review.

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van Westreenen, M., Tiddens, H.A.W.M. New Antimicrobial Strategies in Cystic Fibrosis. Pediatr-Drugs 12, 343–352 (2010). https://doi.org/10.2165/11316240-000000000-00000

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