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Dr Robinson's review of cystic fibrosis (CF) touches on the use of continuous anti-staphylococcal antibiotic prophylaxis.1 Dr Robinson reiterates the oft repeated assertion that there is an association between the use of prophylactic antibiotics and the early acquisition of pulmonary infection withPseudomonas aeruginosa in patients with CF. This putative association has entered CF folklore but is not supported by any published evidence. The paper cited by Robinson describes a pilot study of cephalexin which lasted 2 months.2 A subsequent multicentre randomised placebo controlled trial of cephalexin, commenced in children under 2 years, has been undertaken and its methodology described.3 However, no results have so far appeared in the published literature.
We have recently published an updated systematic review of randomised controlled trials of prophylactic antibiotics in CF.4 This describes data from three studies involving 185 children. We found that fewer children who received prophylaxis from birth had one or more isolates of Staphylococcus aureus over a 3 year period. There was also evidence at 2 years that less time was spent in hospital in the prophylaxis group. The number of children receiving prophylaxis who had one or more isolates ofP aeruginosa over a 3 year period was half that of the control group who had intermittent antibiotic treatment only. This was not, however, statistically significant (Peto odds ratio 0.54, 95% confidence interval 0.23 to 1.26).
The steering group of the North American cephalexin trial have indicated that its results will be published soon (Eliezer Nussbaum, personal communication). However, until there is published evidence from at least one properly designed randomised controlled trial, the proposal that prophylaxis encourages pulmonary infection withP aeruginosa remains entirely speculative.
author's reply I thank Drs Smyth and Walters for their comments concerning the issue of whether antistaphylococcal prophylaxis leads to a higher risk of colonisation with Pseudomonas aeruginosa in patients with cystic fibrosis. I share their concern as to the lack of definitive data supporting this notion and, indeed, tried to illustrate this in my article by stating “There is some evidence that it may be associated . . .”.1-1 I would suggest, however, that the authors' evidence of a lack of association is equally thin—to quote a multicentre trial whose methodology was presented as an abstract some 9 years ago but whose results do not appear to have ever been published in a peer reviewed journal is certainly not basing one's evidence on hard evidence based facts. I did not mention the review by Smyth and Walters1-2 in my own paper as I submitted my review some 18 months before theirs had been published; however, the authors did not include in their own letter discussion of the recent paper by Ratjenet al 1-3 using data from the German CF database which included 639 patients, all under 18 years of age and P aeruginosa negative prior to entry in the study. 48.2% of the patients received continuous antistaphylococcal treatment, 40.4% received intermittent antibiotic treatment, and 11.4% received no antibiotic treatment. While the rate at which patients acquired positive respiratory cultures forStaphylococcus aureus was significantly lower in the group receiving continuous antistaphyloccocal antibiotic treatment than in those receiving no such treatment, patients receiving continuous antistaphyloccocal antibiotic treatment had a significantly higher rate of P aeruginosa acquisition than patients receiving only intermittent or no antibiotic treatment. This difference was especially apparent for children under the age of 6 years. The authors concluded that “continuous therapy with antistaphyloccocal antibiotics directed againstStaph aureus increases the risk of colonisation with P aeruginosa”.
This interesting study I believe again supports my original statement that “there is some evidence that it (continuous antistaphyloccocal antibiotic therapy) may be associated with earlier acquisition ofP aeruginosa”.
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