Management of Patients with Cystic Fibrosis: Defining the Role of Inhaled Tobramycin
Harriet M. Lamb
Karen L. Goa
Cystic fibrosis (CF) is a serious genetically inherited multisystem disease, characterised by symptoms of pancreatic insufficiency, meconium ileus, obstruction/absence of the vas deferens and chronic obstruction, infection and inflammation of the lower respiratory tract. Lung disease, specifically chronic infection caused by Pseudomonas aeruginosa, is the principal cause of morbidity and mortality in patients with CF. Patients with CF require a specialised and integrated programme of care. Proper nutrition, airway clearance and antibacterial therapy are the key components of healthcare for these patients. Inhaled antibacterial therapy, which offers the theoretical benefits of high lung concentrations with minimal risk of systemic toxicity, is sometimes used in this patient group. Inhaled tobramycin, colistin (or colistimethate) and beta-lactam agents (with or without an aminoglycoside) have all been tested as suppressive antipseudomonal therapy, although they have yet to be compared in clinical trials. Recently, tobramycin solution for inhalation (TOBI(R)) has been developed in an attempt to improve on the extemporaneous preparations previously used for this purpose. In patients with CF and confirmed P. aeruginosa infection, 3 courses of a 28-day on/28-day off regimen of inhaled tobramycin (TOBI(R)) significantly improved lung function versus placebo. Patients were permitted to receive other antibiotic treatment as needed. Improvement was sustained for up to 23 months in those who continued the regimen. Inhaled tobramycin also was associated with a 26% reduction in the likelihood of hospitalisation and a 36% reduction in the use of intravenous antipseudomonal antibiotics versus placebo. Although the frequency of bacteria intrinsically resistant to tobramycin did not increase during therapy, fungi (Candida albicans and Aspergillus spp.) were isolated significantly more frequently among tobramycin than placebo recipients. Susceptibility to tobramycin declined steadily among P. aeruginosa during treatment, although the clinical significance of this is difficult to determine. Inhaled tobramycin is generally well tolerated; tinnitus and alteration of the voice occurred in 3 and 13% of patients, respectively. No hearing loss or renal toxicity were reported after 23 months of therapy. Bronchospasm was observed in about 1 in 8 patients. Conclusions: The inhaled formulation of tobramycin is distinguished by a large body of clinical data which should enable clinicians to use the agent appropriately in patients with CF and P. aeruginosa infection. Importantly, for each patient, the risks of hoarseness, fungal coinfection and acquisition cost should be weighed against the benefits of sustained improvement in lung function, reduced hospitalisation, reduced need for parenteral antipseudomonal agents, minimal systemic toxicity and a preservative-free formulation.
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