Evaluation of Legionella PCR Techniques for the Routine Diagnosis of Legionellosis - Full Text View

Sponsors and Collaborators:	Centre Hospitalier Universitaire de Saint Etienne Ministry of Health, France
Information provided by:	Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:	NCT00452153

Purpose

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.

Condition	Intervention
Legionellosis	Procedure: Characterization Legionnella

Study Type:	Interventional
Study Design:	Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Evaluation of Legionella PCR Techniques for the Routine Diagnosis of Legionellosis

Resource links provided by NLM:

MedlinePlus related topics: Pneumonia

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome Measures:

Definite or probable legionellosis [ Time Frame: Inclusion and J30 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Definite legionellosis [ Time Frame: Inclusion and J30 ] [ Designated as safety issue: No ]
Probable legionellosis [ Time Frame: Inclusion and J30 ] [ Designated as safety issue: No ]
Possible legionellosis [ Time Frame: Inclusion and J30 ] [ Designated as safety issue: No ]

Estimated Enrollment:	913
Study Start Date:	March 2007
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Characterization Legionnella: Experimental	Procedure: Characterization Legionnella Characterisation Legionnella by polymerase chain reaction (PCR) Characterization strain of Legionnella by sequencing the 23S-5S ribosomal intergenic spacer region

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

No sputum aspirate

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452153

Contacts

Contact: Philippe Berthelot, MD PhD	00 33 4 77 12 05 92	philippe.berthelot@chu-st-etienne.fr
Contact: Florence Grattard, MD	00 33 4 77 82 81 05	florence.grattard@chu-st-etienne.fr

Locations

France
Urgency unit CHU Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Contact: Alain VIALLON, MD 00 33 4 77 12 05 87 alain.viallon@chu-st-etienne.fr
Sub-Investigator: Alain Viallon, MD
Sub-Investigator: Olivier Marjollet, MD
Sub-Investigator: Yann Leveques, MD
Sub-Investigator: Frédéric Garcia, MD
Sub-Investigator: Marie Cheynet, MD
Sub-Investigator: Floriane Robert, MD
Sub-Investigator: Lionel Cotte, MD
Sub-Investigator: Christophe Berger, MD
Sub-Investigator: Anaclet Ngameni, MD
Sub-Investigator: Matthieu Belin, MD
Sub-Investigator: Alexis Rousset, MD
Sub-Investigator: Pantea Hafezi-Moghaddam, MD
Sub-Investigator: Valerie Pouzet, MD
Sub-Investigator: Baptiste Ehret, MD
Pneumology unit CHU de Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Contact: Jean-Michel Vergnon, MD PhD 00 33 4 77 82 83 14 jean-michel.vergnon@chu-st-etienne.fr
Sub-Investigator: Jean-Michel Vergnon, MD PhD
Sub-Investigator: Isabelle Court-Fortune, MD
Sub-Investigator: Pierre Fournel, MD
Sub-Investigator: Sophie Bayle, MD
Sub-Investigator: Sandra Morgado, MD
Infectious Disease unit CHU de Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Sub-Investigator: Celine Cazorla, MD
Sub-Investigator: Anne Fresard, MD
Sub-Investigator: François Durand, MD
Sub-Investigator: Pascal Fascia, MD
Principal Investigator: Philippe Berthelot, MD PhD
Sub-Investigator: Frederic Lucht, MD PhD
Sub-Investigator: Franck-Olivier Mallaval, MD
Reanimation unit - Hopital Bellevue - CHU de Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Sub-Investigator: Fabrice Zeni, MD PhD
Sub-Investigator: Christophe Venet, MD
Sub-Investigator: Monique Bertrand, MD
Sub-Investigator: Pierre Gery, MD
Sub-Investigator: Dominique Page, MD
Reanimation unit - Hôpital NORD - CHU de Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Sub-Investigator: Christian Auboyer, MD PhD
Sub-Investigator: David Rosay, MD
Sub-Investigator: Richard Jospe, MD
Sub-Investigator: Jerome Morel, MD
Sub-Investigator: Alain Dumont, MD
HMU CHU Saint-Etienne	Recruiting
SAINT-ETIENNE, France, 42055
Sub-Investigator: Bernard Tardy, MD
Sub-Investigator: Yves Pages, MD
Sub-Investigator: Eric Diconne, MD
Sub-Investigator: Stephane Guyomarc'h, MD

Sponsors and Collaborators

Centre Hospitalier Universitaire de Saint Etienne

Ministry of Health, France

Investigators

Principal Investigator:

Philippe Berthelot, PU-PH

CHU-Saint-Etienne

More Information

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, Luck 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, Luck 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, Joannes 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, Luck 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.

Responsible Party:	CHU Saint-Etienne ( Clément CAILLAUX )
Study ID Numbers:	0601072
Study First Received:	March 26, 2007
Last Updated:	June 8, 2009
ClinicalTrials.gov Identifier:	NCT00452153 History of Changes
Health Authority:	France: Ministry of Health

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:

legionellosis
diagnosis of legionellosis
PCR

Study placed in the following topic categories:

Bacterial Infections
Legionellosis
Respiratory Tract Diseases
Respiratory Tract Infections
Gram-Negative Bacterial Infections

Additional relevant MeSH terms:

Bacterial Infections
Legionellosis
Respiratory Tract Diseases
Respiratory Tract Infections
Gram-Negative Bacterial Infections

ClinicalTrials.gov processed this record on September 10, 2009