Publications
4 results found
Davies J, Mossop M, Jonathan I-H, et al., 2024, Chronicity Counts: The Impact of P. aeruginosa, S. aureus, and Co-Infection in Cystic Fibrosis, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X
Davies J, Morales S, Alton E, et al., 2023, Lytic bacteriophage is a promising adjunct to common antibiotics across cystic fibrosis clinical strains and culture models of Pseudomonas aeruginosa infection, Antibiotics, Vol: 12, Pages: 1-14, ISSN: 2079-6382
Bacteriophages (phages) are antimicrobials with resurgent interest that are being investigated for the treatment of antibiotic refractory infection, including for Pseudomonas aeruginosa (Pa) lung infection in cystic fibrosis (CF). In vitro work supports the use of this therapy in planktonic and biofilm culture models; however, consistent data are lacking for efficacy across different clinical Pa strains, culture models, and in combination with antibiotics in clinical use. We first examined the efficacy of a 4-phage cocktail as an adjunct to our CF centre’s first-line systemic combination antibiotic therapy (ceftazidime + tobramycin) for 16 different clinical Pa strains and then determined subinhibitory interactions for a subset of these strains with each antibiotic in planktonic and biofilm culture. When a 4-phage cocktail (4 × 108 PFU/mL) was added to a ceftazidime-tobramycin combination (ceftazidime 16 mg/mL + tobramycin 8 mg/mL), we observed a 1.7-fold and 1.3-fold reduction in biofilm biomass and cell viability, respectively. The four most antibiotic resistant strains in biofilm were very susceptible to phage treatment. When subinhibitory concentrations of antibiotics and phages were investigated, we observed additivity/synergy as well as antagonism/inhibition of effect that varied across the clinical strains and culture model. In general, more additivity was seen with the phage-ceftazidime combination than with phage-tobramycin, particularly in biofilm culture, where no instances of additivity were seen when phages were combined with tobramycin. The fact that different bacterial strains were susceptible to phage treatment when compared to standard antibiotics is promising and these results may be relevant to ongoing clinical trials exploring the use of phages, in particular in the selection of subjects for clinical trials.
Short C, Abkir M, Pinnell S, et al., 2022, Migration is not the perfect answer: How the cross-talk error correction for multiple breath nitrogen washout (MBWN2) parameters differs on directly collected vs. legacy data, Pediatric Pulmonology, Vol: 58, Pages: 328-331, ISSN: 1099-0496
Recently, a cross-talk error with commercial multiple breath nitrogen washout (MBWN2) software was discovered, which produced an absolute over-reading of N2 of approximately 1%, i.e., 2% N2 read as 3%. This caused an extended tail to the washout, and over-estimated lung clearance index (LCI2.5) values. Subsequently an updated and corrected software version has been released. Within the field there have been discussions on how to correct legacy data, whether to migrate or completely “rerun” raw data A-files from the old software into the new corrected software. To our knowledge, no research has been published assessing whether either method is equivalent to directly collecting data in the new corrected software. We prospectively recruited 19 participants, 10 adult healthy controls and 9 people with cystic fibrosis (CF). MBWN2 was performed using the Exhalyzer® D first on the old 3.1.6 software and next, directly on corrected 3.3.1 software. Multiple breath washout (MBW) data directly collected in 3.3.1 was significantly different from both migrated and rerun data. A total of 7 of the 19 participants (37%; 4 CF) had a relative difference in LCI2.5 > 10% for both migrated and rerun data compared to 3.3.1 collected data. Our findings have implications for the Global Lung Initiative MBW project, which is accepting a combination of directly collected, A-file reruns and migrated data to establish normative values. Further, caution must be used in clinical practice when comparing corrected legacy data versus 3.3.1 collected data for clinical interpretation. We recommend that a new baseline is collected directly on 3.3.1. before clinical interpretation and decisions are determined when comparing consecutive MBW tests.
Davies JC, Scott S, Dobra R, et al., 2019, Fair selection of participants in clinical trials: The challenge to push the envelope further, Journal of Cystic Fibrosis, Vol: 18, Pages: e48-e50, ISSN: 1569-1993
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