Praxis Pharmaceutical
Cystic Fibrosis. Treatments
Current therapy and unresolved needs
Antimicrobial treatment strategies for Pseudomonas aeruginosa colonisation or infection in patients with CF must consider not only the immediate benefit of the treatment but also the middle- or long-term repercussions in terms of the development of resistances and their consequences for the patient.
We can distinguish between four different clinical situations, each requiring a different therapeutic approach (7):
Prophylactic treatment. The prophylactic use of antimicrobials to prevent initial P. aeruginosa colonisation has only been reported on an anecdotal basis, and no clear benefits have been found (8).
Treatment in the initial colonisation phase.. This treatment must be started as early as possible and should be aggressive. In effect, any chance which we may have to fully eradicate P. aeruginosafrom the airways of CF patients is found in the early colonisation phase, before the characteristic chronic colonisation has developed (9). This is because in the early stages, the bacterial inoculum within the lungs of CF patients is less intense, and particularly because the P. aeruginosa strains in such stages have conventional characteristics instead of the typical ones inherent to the disease (mucous strains, with hypermutation or resistance to multiple antimicrobial drugs) and that make the bacterium so difficult to eradicate. The use of initial aggressive therapy makes it possible to eradicate P. aeruginosaAs a result, the cultures for this microorganism remain negative even for several years after completing the antimicrobial treatment.
Treatment of chronic colonisation.. This treatment is also known as maintenance or chronic suppressive therapy. Once chronic pulmonary colonisation by P. aeruginosa has occurred, complete eradication becomes virtually impossible - at least from the present management perspective. Once this stage has been reached, the aim of treatment is to minimise the middle- or long-term deleterious effects produced by persistence of the microorganism. The progressive lung damage caused by the continuous inflammation - even in the absence of disease exacerbations – means there is a need for maintenance therapies capable of reducing the bacterial burden (and thus the secondary host inflammatory response) over prolonged periods of time. It has been shown that chronic suppressive therapy (even in the absence of exacerbations) not only avoids the deterioration of lung function but may also favour its recovery (10).
Treatment of acute respiratory exacerbation. On a conceptual basis, such treatment should afford immediate reduction of the bacterial inoculum, which is often increased with respect to its usual levels (11). To this effect, aggressive treatments via the intravenous route are needed, except in the case of mild exacerbations, where orally administered medication is preferred. To date, the efficacy for this purpose of antimicrobials administered via the inhalatory route has not been demonstrated.
References
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- 2. Armstrong DS, Grimwood K, Carlin JB, Carzino R, Gutierrez JP, Hull J, Olinsky A, Phelan EM, Robertson CF, Phelan PD. Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1197-204
- 3. Hull J, Thomson AH. Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis. Thorax. 1998;53: 1018-21
- 4. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003;15:918-51.3
- 5. Henry RL, Mellis CM, Petrovic L. Mucoid Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis. Pediatr Pulmonol. 1992;12:158-61.
- 6. Taccetti G, Repetto T, Procopio E, Farina S, Campana S. Early Pseudomonas aeruginosa colonisation in cystic fibrosis patients. Lancet. 2002 Feb 16;359(9306):625-6.
- 7. Canton R, Cobos N, de Gracia J, Baquero F, Honorato J, Gartner S, Alvarez A, Salcedo A, Oliver A, Garcia-Quetglas E; en representación del gurpo Español de Consenso del Tratamiento Antimicrobiano en el Paciente con Fibrosis Quística. Tratamiento antimicrobiano frente a la colonización por Pseudomonas aeruginosa en el paciente con fibrosis Quística. Arch Bronconeumol. 2005;41 Supl 1:1-25.
- 8. Doring G, Conway SP, Heijerman HG, Hodson ME, Hoiby N, Smyth A, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J. 2000;16:749-67.
- 9. Frederiksen B, Koch C, Hoiby N. Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974-1995). Pediatr Pulmonol. 1999;8:159-66.
- 10. Hoiby N. Prospects for the prevention and control of pseudomonal infection in children with cystic fibrosis. Paediatr Drugs. 2000;2:451-63
- 11. Ramsey BW. Management of pulmonary disease in patients with cystic fibrosis. N Engl J Med. 1996;335:179-88.