Report of the UK Cystic Fibrosis Trust Antibiotic Working Group

6.1 Introduction6. INTRAVENOUS ANTIBIOTICSThere are 5 key questions in the use of intravenous antibiotics in cystic fibrosis (CF) patients and thesewill be covered in turn in this section.• Why treat?• Who should be treated?• Which antibiotics should be used?• What dose, for how long and in what setting should antibiotics be given?• How can we minimise the cumulative side effects of treatment?6.2 Why treat?6.2.1 Early onset of infection and inflammation in CFIn CF, lower respiratory infection begins in the first weeks of life: bronchoalveolar lavage showed thepresence of Staphylococcus aureus in approximately one third of infants at a mean age of 3 months. 1 Asimilar study in older children (mean age 17 months) found S.aureus in 47%, Haemophilus influenzaein 15% and Pseudomonas aeruginosa in 13%. 2 Lower respiratory infection in young children with CFis associated with more frequent wheezing, increased levels of inflammatory mediators, and airtrapping. When infection is successfully treated, inflammatory mediators fall to pre-treatment levels. 3It has been suggested that the presence of pathogenic organisms in the lower respiratory tract sets upa vicious cycle of infection, inflammation and lung damage which leads to bronchiectasis andultimately, respiratory failure and death. Although there is some evidence that the CF genotype itselfmay promote inflammation, 4 there is no doubt that the early treatment of infection is crucial indelaying or halting the inflammatory cycle.6.2.2 Pseudomonas aeruginosaMost CF patients in the UK have developed chronic pulmonary infection with P.aeruginosa by theirlate teens, 5 and this is associated with a more rapid decline in lung function and increased mortality. 6[2+] The organism has innate resistance to many antibiotics, and furthermore it can elude the hostimmune system and the action of antibiotics by forming complex colonies, known as biofilms, ondamaged respiratory epithelium. 7 In young patients with CF there is genetic heterogeneity in isolatesof P.aeruginosa 8 suggesting repeated new infections, but in adults with chronic P.aeruginosa infection,pulmonary exacerbations are usually not caused by a new strain. 9 [2+] However, sensitivity patternsmay change from when the patient is stable to when they have an exacerbation. Antibiotic therapymay be selected on the basis of the last available sputum or cough swab result but should be amendedwhen the culture and sensitivities are available from a sample taken during the exacerbation, if thepatient’s clinical response is poor. Whilst the laboratory report of antibiotic susceptibility is a guide,this will not always correlate with clinical response. 106.2.3 Evidence for the use of intravenous antibioticsAlthough intravenous antibiotics have played a central role in the management of pulmonaryinfection in CF patients for 4 decades, there have only been two studies comparing their action againsta placebo. 11;12 [1-] Both were small (less than 20 patients in each arm) and underpowered. In theearlier of the two (Wientzen et al) 11 there were two deaths and more patients with a poor clinicaloutcome in the placebo group. In the later study of Gold et al 12 there was no difference in clinicalCystic Fibrosis Trust 6.0March 2009