The survival of patients with cystic fibrosis (CF) has improved considerably in the last 10 to 15 years, mainly because of earlier diagnosis, better understanding and management of nutritional problems, and the advent of broad-spectrum antibiotics that have permitted effective control of lung infections caused by Hemophilus influenzae and Staphylococcus aureus organisms. At present the Pseudomonas aeruginosa pathogens present the clinician with constant therapeutic dilemmas. Although the immunologic mechanisms responsible for mucosal damage associated with P aeruginosa lung infections remain poorly understood, recurrent infections due to this group of organisms account for an increased morbidity and mortality. For instance, chronic colonization of the lungs with P aeruginosa during the first 5 years of life is associated with a 20 percent survival to the age of 16 years, but a 95 percent survival when the lungs are unaffected by P aeruginosa. Moreover, the beneficial clinical effects when appropriate antibiotic therapy is given for acute symptomatic exacerbations of lung disease have been well documented in double-blind studies. Whether the regular and periodic use of antibiotic therapy directed at eradicating P aeruginosa from lungs leads to improved survival remains unresolved, although Szaff et al found that survival rates were improved when compared to historic controls.
The characteristic feature of P aeruginosa organisms in CF is their production of an extracellular polysaccharide (slime) that is structurally similar to alginic acid. The lung infections are, on the whole, caused by these mucoid alginate-producing P aeruginosa strains, but most patients lungs become colonized by nonmucoid P aeruginosa. The mucoid P aeruginosa appears to grow as embedded microcolonies in the alginate gel. Thus any toxins so produced can inhibit further host defense mechanisms. diabet glucotror
The antibiotic treatment of acute exacerbations of P aeruginosa lung infections consists of the use of combinations of antibiotic agents, or, following the development of third-generation antibiotics possessing adequate tissue penetration, long half-life, high β-lactamase stability, and relative freedom from undesirable toxic effects, the use of single therapeutic agents.
Since the pathogenesis of respiratory infections due to P aeruginosa in CF remains unresolved, different approaches to management have been developed by various centers. The majority of patients with P aeruginosa symptomatic lung infections are given courses of intravenous antibiotics for a period of 10 to 20 days. Such a scheme requires frequent hospital admissions and so imposes a considerable strain on the patient and his family. Experience with an effective anti-Pseudomonas antibiotic agent remains fairly limited and experimental.
In 1978 we developed a program of outpatient intravenous antibiotic treatment, and in 1982 extended it entirely to home management to improve further the quality of life of patients and their families. Such an approach to the management of acute respiratory exacerbations due to P aeruginosa has been found to be acceptable and very cost-effective.