Pseudomonas aeruginosa in cystic fibrosis patients with c.1652G›A (G551D)‐CFTR treated with ivacaftor—Changes in microbiological parameters. (22nd September 2017) - Millar, B. C.
Summary: What is known and objective: The CFTR potentiator, ivacaftor (IVA), has been widely used in the treatment of cystic fibrosis (CF) patients with the G551D mutation. To date, there has been limited information on the microbiological status of patients on this therapy and no data on the effect (if any) on the in vivo antibiotic susceptibility of Pseudomonas aeruginosa isolated from patients on therapy. Although IVA intervention is not designed per se as anti‐infective, the effect (if any) of this molecule to CF patients' microbiological status merits careful monitoring. Therefore, it was the aim of this observational study to examine the effect in patients, both before and after commencement of IVA therapy, on several commonly reported microbiological markers in CF patients, including (i) bacterial density, (ii) frequency (rate) of isolation of bacterial pathogens, particularly P. aeruginosa, and (iii) antimicrobial susceptibility of these isolates to commonly prescribed oral and iv antibiotics. In addition, we wished to examine the requirements for these antibiotics in CF patients, before and after commencement of IVA therapy. Methods: Archived data from 15 adult cystic fibrosis patients with the c.1652G›A (G551D) mutation were followed from two years pre‐IVA therapy to two years after commencement of IVA therapy. The microbiological parameters examined included (i) oral antibiotic courses taken, (ii) intravenous (iv) antibiotic courses taken, (iii) rate of isolation of non‐mucoid Pseudomonas aeruginosa (NM‐PA) and mucoid P. aeruginosa (M‐PA), (iv) density of NM‐PA and M‐PA and (v) antimicrobial susceptibility of NM‐PA and M‐PA to 11 antibiotics [aminoglycosides, beta‐lactams, polymyxin and fluoroquinolone]. Results and discussion: Following commencement of IVA therapy, patients required less iv antibiotic courses but no change in number of oral antibiotics courses. There was significant reduction in both the rate of isolation and density of M‐PA ( P = .02; P = .006, respectively). In contrast, there was no significant reduction in both the rate of isolation and density of NM‐PA ( P = .90; P = .07, respectively). Antimicrobial susceptibility in NM‐PA and M‐PA was not significantly reduced within any of the antibiotics classes or individual antibiotics examined. Increased susceptibility was noted in the beta‐lactam class for NM‐PA and M‐PA, in particular with ceftazidime. What is new and conclusion: Overall, (i) the requirement for less iv antibiotic therapy, (ii) a reduction in the rate and density of M‐PA and (iii) no reduction in antibiotic susceptibility indicate that microbiological parameters with patients on IVA therapy were not detrimentally affected. Abstract : This study shows that microbiological parameters with patients on ivacaftor (IVA) therapy were not detrimentally affected, as there was a lower requirement iv antibiotic therapy and a reduction in the rate and density of mucoid Pseudomonas aeruginosa (M‐PA). Examination of antibiotic susceptibility, as expressed by Relative Resistance Index, against four classes of antibiotic in (a) total PA, (b) Non‐mucoid PA (NM‐PA) and (c) M‐PA, isolated from patients before and after commencement of ivacaftor therapy, showed no reduction in antibiotic susceptibility. Overall, this study suggests an improvement in the microbiology status of patients on IVA therapy.