Pseudomonas aeruginosa, in cystic fibrosis

McCoy KS, Quitmer AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. (2008) Inhaled aztreonam lysine for chronic airway Pseudomonas Aeruginosa in cystic fibrosis. Am J Respir Crit Care Med 178 921-928. 

Canton R, Cobos N, de Gracia J, et al. Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect. 2005 11 690-703. 

Boucher, J.C., Yu, H., Mudd, M.H., Deretic, V. Mucoid Pseudomonas aeruginosa in cystic fibrosis characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect Immun 65 (1997) 3838-3846. 

Since that time, a significant number of variations on that theme have been placed into clinical trials and, in some cases, such as Aztreonam 28, into commerce. Recently (late 2007, early 2008), this compound was submitted for approval in the EU and the USA as the lysinate salt for the inhalation treatment of Pseudomonas aeruginosa in cystic fibrosis under an Orphan drug category. As of late 2008, the Food and Drug Administration (FDA) was requiring further information and the status of the EU application was not yet known. 

Mpller NE, Eriksen KR, Feddersen C, et al. Chemotherapy against Pseudomonas aeruginosa in cystic fibrosis A study of carbenicillin, azlocillin, or piperacillin in combination with tobramycin. Eur J Respir Dis 1982 63 130-139. 

The use of the aerosol route for delivery of antibiotics for pulmonary infections remains controversial. The majority of pediatric studies have been conducted in children with cystic fibrosis. In these patients distribution of the antibiotic to the desired tissue site is impeded because of the viscosity of the sputum in patients with acute exacerbations of their pulmonary infections [91,92], Long-term studies have demonstrated preventive benefits of aerosolized antibiotics in children with cystic fibrosis who are colonizing Pseudomonas aeruginosa in their lungs but are not acutely ill [93,94], Cyclic administration of tobramycin administered by nebulizer has received FDA approval [95],... 

Casaulta C, Sdioni MH, Weichel M, Crameri R, Jutel M, Daigle I, et al IL-10 controls Aspergillus fumigatus- and Pseudomonas aeruginosa-specHic T-cell response in cystic fibrosis. Pediatr Res 2003 53 313-319. 

Pseudomonas aeruginosa is another major human pathogen that causes disease in patients with impaired host defenses.27 Ps. aeruginosa is primarily associated with ultimately fatal chronic respiratory infection in cystic fibrosis and other forms of bronchiectasis.28 Despite strong inflammatory... 

Deretic, V., M. J. Schurr, J. C. Boucher, and D. W. Martin 1994. Conversion of Pseudomonas aeruginosa to mucoidy in cystic fibrosis Environmental stress and regulation of bacterial virulence by alternative sigma factors. Journal of Bacteriology 176 2773-2780. 

Henry, R.L., Mellis, C.M., Petrovic, L. Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis. Pediatr Pulmonol 12 (1992) 158-161. 

B. Epidemiology of chronic Pseudomonas aeruginosa infections in cystic fibrosis. J Infect Dis 170 (1994) 1616-1621. 

Thomas, S.R., Ray, A., Hodson, M.E., Pitt, T.L. Increased sputum amino acid concentrations and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease. Thorax 55 (2000) 795-797. 

C., Walter, S. Infections with Pseudomonas aeruginosa in patients with cystic fibrosis. Behring Inst Mitt (1997) 249-255. 

Yoon SS, Hassett DJ. Chronic Pseudomonas aeruginosa infection in cystic fibrosis airway disease metabolic changes that unravel novel drug targets. Expert Rev. Anti. Infect. Ther. 2004 2 611-623. 

Jensen T, Pedersen SS, Nielsen CH, Hoiby N, Koch C. The efficacy and safety of ciprofloxacin and ofloxacin in chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Antimicrob Chemother 1987 20(4) 585-94. 

Ernst RK, Yi EC, Guo L, Lim KB, Burns JL, Hackett M, Miller SI. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 1999 286(5444) 1561-5. 

Valerius NH, Koch C, Hoiby N. Prevention of chronic Pseudomonas aeruginosa colonization in cystic fibrosis by early treatment. Lancet 338 725-726, 1991. 

Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 23 330-335, 1997. 

Vasquez C, Municio M, Corera M. Early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Acta Paediatr 82 308-309, 1993. 

Heinzl B, Eber E, Oberwaldner B, Haas G, Zach MS. Effects of inhaled gentamicin prophylaxis on acquisition of Pseudomonas aeruginosa in children with cystic fibrosis a pilot study. Pediatr Pulmonol 33 32-37, 2002. 

Jensen T, Pedersen SS, Game S. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 19 831-838, 1987. 

Grimwood K, Semple RA, Rabin HR, et al. Elevated exoenzyme expression by Pseudomonas aeruginosa is correlated with exacerbations of lung disease in cystic fibrosis. Pediatr Pulmonol 1993 15 135-139. 

Mpller NE, Hpiby N. Antibiotic treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. Scand J Infect Dis 1981 24(suppl) 87-91. 

Friis B. Chemotherapy of chronic infections with mucoid Pseudomonas aeruginosa in lower airways of patients with cystic fibrosis. Scand J Infect Dis 1979 11 211-217. 

Infections in cystic fibrosis are often due to Staphylococcus aureus, Haemophilus influenzae or Pseudomonas aeruginosa. Infecting organisms need to be identified so that the most appropriate antibiotics can be used. Antibiotics used to treat respiratory infections in cystic fibrosis commonly include ciprofloxacin, erythromycin, flu-cloxacillin and amoxicillin. However, specialist individual therapy is essential for maximum benefit to the patient and avoidance of the development of resistant strains of bacteria. 

Pulmonary Pseudomonas aeruginosa infections in cystic fibrosis... 

An important characteristic of microbial biofilms is their innate resistance to immune system and antibiotic killing (89, 90). This has made microbial biofilms a common and difficult-to-treat cause of medical infections (87,91,92). It has recently been estimated that over 60% of the bacterial infections currently treated in hospitals are caused by bacterial biofilms (91). Several ehronic infections (e.g. respiratory infections caused by Pseudomonas aeruginosa in the cystic fibrosis lung. Staphylococcal lesions in endocarditis, and bacterial prostatitis, primarily caused by Escherichia coli) have been shown to be mediated by biofilms (93). More notably, biofilms (particularly of Staphylococcus aureus, P. aeruginosa, and E. coli) are also a major cause of infections associated with medical implants (94, 95). The number of implant-associated infections approaches 1 million per year in the United States alone, and their direct medical costs exceed 3 billion annually (96). Thus, there is an urgent need to find novel approaches to eradicate biofilms. 

---