Evaluation of Legionella PCR Techniques for the Routine Diagnosis of Legionellosis

• ClinicalTrials.gov Identifier: NCT00452153
• Recruitment Status: Terminated
• First Posted: March 27, 2007
• Last Update Posted: July 29, 2015
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Tracking Information

• First Submitted Date: March 26, 2007
• First Posted Date: March 27, 2007
• Last Update Posted Date: July 29, 2015
• Study Start Date: March 2007
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 8, 2009): Definite or probable legionellosis [ Time Frame: Inclusion and J30 ]
• Original Primary Outcome Measures (submitted: March 26, 2007): Definite or probable legionellosis

Current Secondary Outcome Measures (submitted: June 8, 2009)

• Definite legionellosis [ Time Frame: Inclusion and J30 ]
• Probable legionellosis [ Time Frame: Inclusion and J30 ]
• Possible legionellosis [ Time Frame: Inclusion and J30 ]

Original Secondary Outcome Measures (submitted: March 26, 2007)

• Definite legionellosis
• Probable legionellosis
• Possible legionellosis

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Legionella PCR Techniques for the Routine Diagnosis of Legionellosis
• Official Title: Evaluation of Legionella PCR Techniques for the Routine Diagnosis of Legionellosis
• Brief Summary: The validity of molecular techniques for the diagnosis of legionellosis is not known. Although PCR can detect Legionella pneumophila (responsible for 80% of legionellosis) and other Legionella species, this test is not recommended in standard guidelines to assess this diagnostic, by contrast to culture of sputum, serology and urine antigen. The aim of this study is to evaluate Legionella PCR techniques, performed directly onto the sputum aspirates, for the routine diagnosis of pneumonia in adults' patients admitted to hospital. This study implicates 3 University hospitals (Lyon, Grenoble and Saint-Etienne) in collaboration with the French reference center of legionellosis for a previous duration of one year. In addition to the usual diagnostic tests that are performed when pneumonia is suspected, real-time PCR will be added for the detection and differentiation of Legionella. Hypothesizing the inclusion of 1000 pneumonia in this study, the predictable number of newly-detected legionellosis will be approximately 60 to 70 cases. According to a predefined algorithm, cases of legionellosis will be classified as definite or probable. Sensitivity and specificity of the real-time PCR will be calculated according to this classification. This study is intended to validate real-time PCR as a tool for the rapid diagnosis of legionellosis, allowing to optimize the antibiotic treatment of pneumonia. PCR techniques can also contribute to the better detection and differentiation of Legionella sp infections that are not documented accurately by routine microbiologic tests.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Legionellosis

Intervention

Procedure: Characterization Legionnella

• Characterisation Legionnella by polymerase chain reaction (PCR)
• Characterization strain of Legionnella by sequencing the 23S-5S ribosomal intergenic spacer region

Study Arms

Experimental: Characterization Legionnella

Characterization Legionnella by polymerase chain reaction (PCR)

Intervention: Procedure: Characterization Legionnella

Publications *

• Squier CL, Stout JE, Krsytofiak S, McMahon J, Wagener MM, Dixon B, Yu VL. A proactive approach to prevention of health care-acquired Legionnaires' disease: the Allegheny County (Pittsburgh) experience. Am J Infect Control. 2005 Aug;33(6):360-7.
• Decludt B, Campese C, Lacoste M, Che D, Jarraud S, Etienne J. Clusters of travel associated legionnaires' disease in France, September 2001- August 2003. Euro Surveill. 2004 Feb;9(2):12-3.
• Grattard F, Berthelot P, Reyrolle M, Ros A, Etienne J, Pozzetto B. Molecular typing of nosocomial strains of Legionella pneumophila by arbitrarily primed PCR. J Clin Microbiol. 1996 Jun;34(6):1595-8.
• Aurell H, Etienne J, Forey F, Reyrolle M, Girardo P, Farge P, Decludt B, Campese C, Vandenesch F, Jarraud S. Legionella pneumophila serogroup 1 strain Paris: endemic distribution throughout France. J Clin Microbiol. 2003 Jul;41(7):3320-2.
• Gaia V, Fry NK, Afshar B, Lück PC, Meugnier H, Etienne J, Peduzzi R, Harrison TG. Consensus sequence-based scheme for epidemiological typing of clinical and environmental isolates of Legionella pneumophila. J Clin Microbiol. 2005 May;43(5):2047-52.
• Wang EE, Manson B, Corey M, Bernard K, Prober CG. False positivity of Legionella serology in patients with cystic fibrosis. Pediatr Infect Dis J. 1987 Mar;6(3):256-9.
• Plouffe JF, File TM Jr, Breiman RF, Hackman BA, Salstrom SJ, Marston BJ, Fields BS. Reevaluation of the definition of Legionnaires' disease: use of the urinary antigen assay. Community Based Pneumonia Incidence Study Group. Clin Infect Dis. 1995 May;20(5):1286-91.
• Helbig JH, Uldum SA, Bernander S, Lück PC, Wewalka G, Abraham B, Gaia V, Harrison TG. Clinical utility of urinary antigen detection for diagnosis of community-acquired, travel-associated, and nosocomial legionnaires' disease. J Clin Microbiol. 2003 Feb;41(2):838-40.
• Grattard F, Ginevra C, Riffard S, Ros A, Jarraud S, Etienne J, Pozzetto B. Analysis of the genetic diversity of Legionella by sequencing the 23S-5S ribosomal intergenic spacer region: from phylogeny to direct identification of isolates at the species level from clinical specimens. Microbes Infect. 2006 Jan;8(1):73-83. Epub 2005 Aug 8.
• Hayden RT, Uhl JR, Qian X, Hopkins MK, Aubry MC, Limper AH, Lloyd RV, Cockerill FR. Direct detection of Legionella species from bronchoalveolar lavage and open lung biopsy specimens: comparison of LightCycler PCR, in situ hybridization, direct fluorescence antigen detection, and culture. J Clin Microbiol. 2001 Jul;39(7):2618-26.
• Templeton KE, Scheltinga SA, Sillekens P, Crielaard JW, van Dam AP, Goossens H, Claas EC. Development and clinical evaluation of an internally controlled, single-tube multiplex real-time PCR assay for detection of Legionella pneumophila and other Legionella species. J Clin Microbiol. 2003 Sep;41(9):4016-21.
• Welti M, Jaton K, Altwegg M, Sahli R, Wenger A, Bille J. Development of a multiplex real-time quantitative PCR assay to detect Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae in respiratory tract secretions. Diagn Microbiol Infect Dis. 2003 Feb;45(2):85-95.
• Reischl U, Linde HJ, Lehn N, Landt O, Barratt K, Wellinghausen N. Direct detection and differentiation of Legionella spp. and Legionella pneumophila in clinical specimens by dual-color real-time PCR and melting curve analysis. J Clin Microbiol. 2002 Oct;40(10):3814-7.
• Ginevra C, Barranger C, Ros A, Mory O, Stephan JL, Freymuth F, Joannès M, Pozzetto B, Grattard F. Development and evaluation of Chlamylege, a new commercial test allowing simultaneous detection and identification of Legionella, Chlamydophila pneumoniae, and Mycoplasma pneumoniae in clinical respiratory specimens by multiplex PCR. J Clin Microbiol. 2005 Jul;43(7):3247-54.
• Helbig JH, Bernander S, Castellani Pastoris M, Etienne J, Gaia V, Lauwers S, Lindsay D, Lück PC, Marques T, Mentula S, Peeters MF, Pelaz C, Struelens M, Uldum SA, Wewalka G, Harrison TG. Pan-European study on culture-proven Legionnaires' disease: distribution of Legionella pneumophila serogroups and monoclonal subgroups. Eur J Clin Microbiol Infect Dis. 2002 Oct;21(10):710-6. Epub 2002 Oct 18.
• Wellinghausen N, Frost C, Marre R. Detection of legionellae in hospital water samples by quantitative real-time LightCycler PCR. Appl Environ Microbiol. 2001 Sep;67(9):3985-93.
• Woodhead M. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir J Suppl. 2002 Jul;36:20s-27s. Review.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 27, 2015): 200
• Original Enrollment (submitted: March 26, 2007): 913
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Written informed consent
• Patient affiliated to social insurance
• Community acquired or nosocomial pneumonia

Exclusion Criteria:

• No sputum aspirate

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00452153
• Other Study ID Numbers: 0601072
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• Study Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France

Investigators

• Principal Investigator: Philippe Berthelot, PU-PH; CHU-Saint-Etienne

• PRS Account: Centre Hospitalier Universitaire de Saint Etienne
• Verification Date: July 2015