Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients

Yvonne C W Yau; Felix Ratjen; Elizabeth Tullis; Pearce Wilcox; Andreas Freitag; Mark Chilvers; Hartmut Grasemann; James Zlosnik; David Speert; Mary Corey; Sanja Stanojevic; Larissa Matukas; Timothy Ronan Leahy; Sarah Shih; Valerie Waters

doi:10.1016/j.jcf.2014.09.013

Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients

J Cyst Fibros. 2015 Mar;14(2):262-6. doi: 10.1016/j.jcf.2014.09.013. Epub 2014 Oct 30.

Authors

Yvonne C W Yau¹, Felix Ratjen², Elizabeth Tullis³, Pearce Wilcox⁴, Andreas Freitag⁵, Mark Chilvers⁶, Hartmut Grasemann⁷, James Zlosnik⁸, David Speert⁹, Mary Corey¹⁰, Sanja Stanojevic¹¹, Larissa Matukas¹², Timothy Ronan Leahy¹³, Sarah Shih¹⁴, Valerie Waters¹⁵

Affiliations

¹ Division of Microbiology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Yvonne.Yau@sickkids.ca.
² Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Felix.Ratjen@sickkids.ca.
³ Division of Respirology, Department of Medicine, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada; Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Electronic address: Tullise@smh.ca.
⁴ Division of Respiratory Medicine, Department of Medicine, St Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada. Electronic address: PWilcox@providencehealth.bc.ca.
⁵ Division of Respiratory Medicine, Department of Medicine, Hamilton Health Sciences Center, McMaster University, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada. Electronic address: freitaga@mcmaster.ca.
⁶ Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, 4480 Oak Street, Vancouver, British Columbia V6H 3N1, Canada. Electronic address: mchilvers@cw.bc.ca.
⁷ Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Hartmut.Grasemann@sickkids.ca.
⁸ Division of Infectious Diseases, Department of Pediatrics, Centre for Understanding and Preventing Infection in Children, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: jzlosnik@cfri.ubc.ca.
⁹ Division of Infectious Diseases, Department of Pediatrics, Centre for Understanding and Preventing Infection in Children, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: dspeert@cfri.ubc.ca.
¹⁰ Child Evaluative Health Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Mary.Corey@sickkids.ca.
¹¹ Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Sanja.Stanojevic@sickkids.ca.
¹² Division of Microbiology, Department of Laboratory Medicine, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Electronic address: Matukasl@smh.ca.
¹³ Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Ronan.Leahy@olchc.ie.
¹⁴ Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: sarah.shih@ucdconnect.ie.
¹⁵ Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address: Valerie.Waters@sickkids.ca.

PMID: 25453872
DOI: 10.1016/j.jcf.2014.09.013

Abstract

This study aimed to determine whether antimicrobial susceptibility testing of Pseudomonas aeruginosa grown as a biofilm, rather than planktonically, improves efficacy of antibiotic treatment for pulmonary exacerbations. This was a multicenter randomized, double-blind controlled trial of 14 days of intravenous antibiotic treatment for pulmonary exacerbations chosen based on conventional vs. biofilm antimicrobial susceptibility results in CF patients with chronic P. aeruginosa infection. There were 74 exacerbations in 39 patients. A total of 46% (12/26) exacerbations in the conventional group compared to 40% (19/48) exacerbations in the biofilm group achieved a ≥3 log drop in P. aeruginosa sputum density (difference -0.03, 95% CI -0.5 to 0.4, p=0.9). Lung function improvements were similar in both groups. Biofilm antimicrobial susceptibility testing did not lead to improved microbiological or clinical outcomes compared to conventional methods in the treatment of pulmonary exacerbations in CF patients with chronic P. aeruginosa.

Trial registration: ClinicalTrials.gov NCT00786513.

Keywords: Antibiotics; Biofilm; Pseudomonas aeruginosa; Pulmonary exacerbation.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Anti-Bacterial Agents* / classification
Anti-Bacterial Agents* / therapeutic use
Biofilms* / drug effects
Biofilms* / growth & development
Canada
Child
Cystic Fibrosis* / complications
Cystic Fibrosis* / microbiology
Double-Blind Method
Female
Humans
Male
Microbial Sensitivity Tests* / methods
Microbial Sensitivity Tests* / statistics & numerical data
Pseudomonas Infections* / diagnosis
Pseudomonas Infections* / drug therapy
Pseudomonas Infections* / etiology
Pseudomonas aeruginosa* / drug effects
Pseudomonas aeruginosa* / physiology
Reproducibility of Results
Respiratory Function Tests / methods
Sputum / drug effects
Sputum / microbiology
Treatment Outcome

Substances

Anti-Bacterial Agents

Associated data

ClinicalTrials.gov/NCT00786513