Report of the UK Cystic Fibrosis Trust Antibiotic Working Group

4. ORAL ANTIBIOTICS IN CYSTIC FIBROSISWe are grateful to Sian Edwards (Royal Brompton Hospital) for her assistance in writing this section.4.1 IntroductionIn the absence of appropriate antibiotic treatment, the abnormal respiratory secretions of the patientwith CF soon become infected with any or all of Staphylococcus aureus, Haemophilus influenzae andPseudomonas aeruginosa. Eradication of a particular organism is likely easier in the early stages ofinfection; this may be achieved by using an intravenous antibiotic when the same drug given orallyhas failed – even though the organism appears to be fully sensitive to the oral drug.4.2 Treatment of meticillin-sensitive Staphylococcus aureus (MSSA) infectionMSSA is clearly a significant pathogen in CF patients. The aim of treatment is to prevent infectionwith, or eradicate MSSA infection from the respiratory tract4.2.1 Prophylactic anti-staphylococcal antibiotics (Option 1) (section 8.1)A Cochrane review has shown that continuous, anti-staphylococcal antibiotic prophylaxis, with anarrow spectrum antibiotic such as flucloxacillin, from diagnosis until the age of 3 years, is effectivein reducing the incidence of infection with MSSA. 1 [1++] There is currently no evidence that thisregimen increases the incidence of P.aeruginosa. However, an improvement in clinical outcomes withprophylaxis has not been shown. This is in part due to the lack of good data from randomisedcontrolled trials, which have rightly been called for by the reviewers. The main safety concern raisedis selection for P.aeruginosa infection with the use of broad spectrum antibiotics such as cephalexin.A US CF Foundation multicentre controlled trial of long-term cephalexin included 209 children lessthan 2 years old with mild chest involvement. Only 119 children finished the study. After 5 years,although the treated children failed to demonstrate any significant clinical advantage, they had fewerrespiratory cultures positive for S.aureus (6% in the cephalexin group versus 30% of controls) butmore were positive for P.aeruginosa (26% of the cephalexin group versus 14% of controls). 2 [1-]Evidence from the German CF Registry also supports this finding. 3 [2-] Thus the safety ofprophylactic, broad spectrum, oral cephalosporins must be questioned although there is currently noevidence to suggest that a narrow spectrum antibiotic, such as flucloxacillin (widely used in the UK)poses such a risk.4.2.2 Intermittent antibiotics (Option 2)An alternative approach to long-term flucloxacillin from diagnosis is a two to four week course of oneor two appropriate antibiotics whenever MSSA grows from respiratory cultures. There are no formaltrials of this approach, nor can particular doses or duration be recommended.4.2.3 Secondary prevention of MSSA infection (Option 3)Clinics which do not prescribe routine prophylactic anti-staphylococcal antibiotics will considerprescribing these long-term if MSSA is isolated repeatedly. There is no evidence to guide the clinicianwhen to institute this policy, or with what antibiotic regimen, or for how long it should be continued.Cystic Fibrosis Trust 4.0March 2009