Early antibiotic treatment for Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing two different protocols
- Giovanni Taccetti1,
- Elisa Bianchini2,
- Lisa Cariani3,
- Roberto Buzzetti4,
- Diana Costantini5,
- Francesca Trevisan1,
- Lucia Zavataro1,
- Silvia Campana1 on behalf of the Italian Group for P aeruginosa eradication in cystic fibrosis*
- 1Department of Sciences for Woman and Child's Health, University of Florence, Cystic Fibrosis Centre, Anna Meyer Children's University Hospital, Florence, Italy
- 2Centro Coordinamento Sperimentazioni Cliniche-ITT, AOU Careggi-Pad. San Damiano, Florence, Italy
- 3Laboratory for Cystic Fibrosis Microbiology, Fondazione IRCCS, Ca' Granda—Ospedale Maggiore Policlinico, Milano, Italy
- 4Clinical Epidemiologist, Bergamo, Italy
- 5Cystic Fibrosis Centre, Fondazione IRCCS, Ca' Granda—Ospedale Maggiore Policlinico, Milano, Italy
- Correspondence to Dr Giovanni Taccetti, Cystic Fibrosis Centre, Anna Meyer Children's University Hospital, Viale Pieraccini 24, Firenze 50139, Italy;
Contributors The trial was designed by GT, LC, RB, DC, FT, LZ and SC. LZ coordinated the randomisation unit and kept the randomisation list. The trial was coordinated in their respective CF Centres by R Gagliardini (Ancona), R Padoan (Brescia), L Ratclif (Cerignola), M Ambroni (Cesena), G Taccetti (Firenze), R Casciaro, L Minicucci (Genova), A Cosimi, T Borio (Gualdo Tadino), A Negri (Livorno), F Forte (Matera), G Vieni, C Zinnarello (Messina), D Costantini, L Claut (Milano), E Fiscarelli, V Lucidi (Roma), M Collura (Palermo). All the coordinators contributed to the interpretation of data in their centres. GT, EB, LC, RB, DC, FT, LZ and SC wrote the first draft of the paper, which all authors reviewed. EB coordinated statistical analyses, performed interim analyses and the final analysis, and wrote the Results section.
- Received 22 July 2011
- Accepted 26 January 2012
- Published Online First 29 February 2012
Background Pseudomonas aeruginosa chronic pulmonary infection is an unfavourable event in cystic fibrosis. Bacterial clearance is possible with an early antibiotic treatment upon pathogen isolation. Currently, no best practice exists for early treatment. The efficacy of two different regimens against initial P aeruginosa infection was assessed.
Methods In a randomised, open-label, parallel-group study involving 13 centres, the superiority of inhaled tobramycin/oral ciprofloxacin compared with inhaled colistin/oral ciprofloxacin (reference treatment) over 28 days was evaluated. Patients were eligible if they were older than 1 year with first or new P aeruginosa isolation. Treatments were assigned equally by centralised balanced randomisation, stratified by age and forced expiratory volume in 1 s values. The participants and those giving the intervention were not masked to arm assignments. The primary endpoint was P aeruginosa eradication, defined as three successive negative cultures in 6 months. Analysis was by intention to treat. This trial was registered with EudraCT, number 2008-006502-42.
Results 105 patients were assigned to inhaled colistin/oral ciprofloxacin (arm A) and 118 to inhaled tobramycin/oral ciprofloxacin (arm B). All patients were analysed. P aeruginosa was eradicated in 66 (62.8%) patients in arm A and in 77 (65.2%) in arm B (OR 0.90, 95% CI 0.52 to 1.55, p=0.81). Following treatment, an increase in Stenotrophomonas maltophilia was noted (OR 3.97, 95% CI 2.27 to 6.94, p=0.001) with no differences between the two arms (OR 0.89, 95% CI 0.44 to 1.78, p=0.88).
Conclusions No superiority of treatment under study was demonstrated in comparison to the reference treatment. Early eradication treatment was associated with an increase in S maltophilia.
- P aeruginosa
- cystic fibrosis
- early eradication treatment
- inhaled antibiotics
- aspergillus lung disease
- bacterial infection
- cystic fibrosis
- opportunist lung infections
- paediatric lung disease
- respiratory infection
- bacterial infection
- clinical epidemiology
- cystic fibrosis
↵* All members mentioned as Italian Group for P aeruginosa eradication in cystic fibrosis contributed to the interpretation of the data, commented extensively, revised the report critically, and approved the final version. GT had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Microbiological analyses were performed in their respective CF Centres by E Manso (Ancona), A D'Aprile (Cerignola), T Borio (Gualdo Tadino), S Campana, N Ravenni, D Dolce, P Cocchi, G Mergni (Firenze), L Cariani, G Defilippi (Milano), T Pensabene (Palermo), E Fiscarelli (Roma—Ospedale Bambino Gesù). L Cariani and G Defilippi performed molecular analyses on P aeruginosa strains.
Funding Italian Cystic Fibrosis Research Foundation (Grant FFC#17/2007) with the contribution of ‘Delegazione FFC di Vicenza’.
Competing interests None to declare.
Patient consent Obtained.
Ethics approval Ethics Committee of Meyer Hospital (Florence, Italy).
Provenance and peer review Not commissioned; externally peer reviewed.
Members of Italian Group for P. aeruginosa eradication in cystic fibrosis Rolando Gagliardini, Esther Manso, Ospedali Riuniti di Ancona, Ancona, Italy; Rita Padoan, Elena Soncini, Clinica Pediatrica, Ospedale dei Bambini, AO Spedali Civili Brescia, Brescia, Italy; Angelica D'Aprile, Luigi Ratclif, Ospedale G Tatarella, Cerignola, Italy; Maura Ambroni, Divisione di Pediatria e Patologia Neonatale, Ospedale Bufalini, Cesena, Italy; Rosaria Casciaro, Laura Minicucci, Ospedale G Gaslini Divisione Pediatria I Genova, Italy; Tatiana Borio, Angelo Cosimi, Ospedale di Gubbio-Gualdo Tadino, Gualdo Tadino, Italy; Vanessa Boni, Gemma Braccini, Priscilla Cocchi, Daniela Dolce, Filippo Festini, Valeria Galici, Gianfranco Mergni, Novella Ravenni, Sergio Zuffo, Anna Meyer Children's University Hospital, Department of Sciences for Woman and Child's Health - University of Florence Florence, Italy; Amalia Negri, Divisione di Pediatria, Ospedale di Livorno, Livorno, Italy; Fabio Forte, Divisione di Pediatria e Neonatologia Dipartimento Donna, Maternità e Infanzia, Ospedale di Matera, Matera, Italy; Giuseppe Vieni, Clara Zinnarello, Ospedale “G Martino”, Messina, Italy; Laura Claut, Gloria Defilippi, Divisione Pediatria dell'Università degli Studi di Milano Fondazione IRCCS, Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy; Ersilia Fiscarelli, Ospedale Pediatrico Bambino Gesù, Roma, Italy; Mirella Collura, Tiziana Pensabene, Divisione Pediatria Ospedale dei Bambini “G. Di Cristina”, Palermo, Italy.