Ana C Blanchard1, Ashley M Rooney2, Yvonne Yau3, Yu Zhang4, Patrick J Stapleton5, Eric Horton6, Michelle Klingel7, Sanja Stanojevic8, Felix Ratjen9, Bryan Coburn10, Valerie Waters11. 1. Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Ana.blanchard@sickkids.ca. 2. Division of Infectious Diseases, Department of Medicine, University Health Network, University of Toronto, 101 College St, Toronto, ON M5G 1L7, Canada. Electronic address: Ashley.rooney@mail.utoronto.ca. 3. Division of Microbiology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Yvonne.yau@sickkids.ca. 4. Division of Infectious Diseases, Department of Medicine, University Health Network, University of Toronto, 101 College St, Toronto, ON M5G 1L7, Canada. Electronic address: Yu.Zhang@uhnresearch.ca. 5. Division of Microbiology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Patrick.stapleton@sickkids.ca. 6. Translational Medicine Research Program, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Eric.horton@sickkids.ca. 7. Translational Medicine Research Program, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Michelle.klingel@sickkids.ca. 8. Translational Medicine Research Program, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Sanja.stanojevic@sickkids.ca. 9. Translational Medicine Research Program, Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Felix.ratjen@sickkids.ca. 10. Division of Infectious Diseases, Department of Medicine, University Health Network, University of Toronto, 101 College St, Toronto, ON M5G 1L7, Canada. Electronic address: Bryan.coburn@utoronto.ca. 11. Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Canada. Electronic address: Valerie.waters@sickkids.ca.
Abstract
BACKGROUND: Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients. METHODS: Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS). DNA concentrations were compared in patients in whom AET was successful (Eradicated) to those with persistently positive sputum cultures (Persistent). RESULTS: Forty-seven patients were included. AET was successful in 32 cases (68%), but failed in 15 cases (32%). Median sputum Pa-specific DNA concentration preceding the positive sputum culture was 2.2 × 10-6 μg/mL in Eradicated cases compared to 3 × 10-5 μg/mL in Persistent cases (p = 0.14). There was no significant difference in DNA concentration in the last sputum sample prior to culture positivity, nor in maximal DNA values. There was also no difference in sputum Pa DNA concentrations in patients who had a mucoid (compared to non-mucoid) Pa infection. CONCLUSIONS: Pediatric CF patients with new-onset Pa infections have detectable Pa-specific DNA in the year preceding a positive culture, however, there is no significant difference in Pa DNA concentrations between patients in whom AET is successful compared to those in whom it fails. Therefore, early molecular detection of Pa may not lead to improved eradication success rates. Crown
BACKGROUND:Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients. METHODS: Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS). DNA concentrations were compared in patients in whom AET was successful (Eradicated) to those with persistently positive sputum cultures (Persistent). RESULTS: Forty-seven patients were included. AET was successful in 32 cases (68%), but failed in 15 cases (32%). Median sputum Pa-specific DNA concentration preceding the positive sputum culture was 2.2 × 10-6 μg/mL in Eradicated cases compared to 3 × 10-5 μg/mL in Persistent cases (p = 0.14). There was no significant difference in DNA concentration in the last sputum sample prior to culture positivity, nor in maximal DNA values. There was also no difference in sputum Pa DNA concentrations in patients who had a mucoid (compared to non-mucoid) Pa infection. CONCLUSIONS: Pediatric CF patients with new-onset Pa infections have detectable Pa-specific DNA in the year preceding a positive culture, however, there is no significant difference in Pa DNA concentrations between patients in whom AET is successful compared to those in whom it fails. Therefore, early molecular detection of Pa may not lead to improved eradication success rates. Crown
Authors: Peter H Gilligan; Damian G Downey; J Stuart Elborn; Patrick A Flume; Sebastian Funk; Deirdre Gilpin; Timothy J Kidd; John McCaughan; B Cherie Millar; Philip G Murphy; Jacqueline C Rendall; Michael M Tunney; John E Moore Journal: J Clin Microbiol Date: 2018-08-27 Impact factor: 5.948