Author(s): Steven P Conway [[dagger]] 1 , Daniel G Peckham 2 , Miles Denton 3 , Keith, G Brownlee 4
cystic fibrosis; inhaled antibiotics; intravenous; macrolide; MRSA infection; rhDNase
Cystic fibrosis (CF) is the most common autosomal recessive inherited disease in the caucasian population, with a frequency of one in 2500-3000 live births and a heterozygote carrier rate of approximately one in 25. The mutation is found in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7. Over 1000 different mutations have been identified but in our own region the diagnosis can be confirmed in 88% of patients by searching for the 33 most common mutations. Over 80% are heterozygote for the δF508 mutation, a triple-base pair deletion in the DNA sequence resulting in the loss of phenylalanine at position 508 in the 1480 amino acid chain. The mutant CFTR protein cannot fold properly and is degraded before reaching the plasma membrane.
Without normal CFTR protein there is excess sodium and defective chloride transport across the apical membrane of secretory epithelial cells with dehydration of the surface epithelium and abnormal ion concentrations in the surface liquids. Diagnostic tests for CF exploit this ionic imbalance. Sweat collected after pilocarpine iontophoresis stimulation shows raised chloride and sodium levels. An abnormal negative potential difference can be measured across the nasal mucosa. The clinical consequence is a multisystem disease involving predominantly the respiratory, gastroenterology, hepatobiliary and male reproductive systems. Patients are susceptible to recurrent respiratory infection with a variety of micro-organisms but especially Pseudomonas aeruginosa , Burkholderia cepacia complex, Staphylococcus aureus , Haemophilus influenzae , and Aspergillus species. Respiratory failure is the cause of death in approximately 80% of patients  . Lack of pancreatic enzymes and bicarbonate results in steatorrhoea and malnutrition. Abnormal gut motility results in acute obstruction. Liver disease may progress from focal biliary fibrosis to cirrhosis with splenomegaly, varices and cirrhosis. Men with CF are almost universally infertile due to bilateral absence of the vas deferens.
Patients with CF should be monitored at regular and frequent intervals, at least every 3 months, for early detection of deterioration  . Treatment is mostly directed at the life-threatening aspects of this multisystem disease: preventing respiratory infection as much as possible, minimizing lung damage by prompt treatment of acute infective exacerbations and use of anti-inflammatory therapies, maintaining normal growth and nutrition and potentially reducing the risk of liver disease progressing to cirrhosis. As a consequence of this multidirectional approach patients may find themselves prescribed at least seven to ten different treatments every day. The physician needs to evaluate the potential benefits of new drugs and new applications of established treatments, taking into account the patient's quality of life and the escalating cost of CF care. In this article, the authors review a small, but important, section of therapies and assess how they can best be used as part of the optimal management of patients with CF. The topics covered are eradication regimens for early or recurrent P. aeruginosa infection, inhaled tobramycin therapy, regular versus on-demand intravenous antipseudomonal antibiotics, antibiotic treatment of...