Scolaris Content Display Scolaris Content Display

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis

Esta versión no es la más reciente

ver la versión actual 02 junio 2023
Contraer todo Desplegar todo

Referencias

Gibson 2003 {published data only}

Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. A randomized, controlled trial of inhaled tobramycin in young children with cystic fibrosis: Eradication of pseudomonas from the lower airway [abstract]. Pediatric Pulmonology 2002;Suppl 24:300. [CFGD Register: PI151c]
Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. Online Supplement to 'Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis'. [online]. American Journal of Respiratory and Critical Care Medicine 2003;167(6):841 Online. [CFGD Register: PI151e]
Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. American Journal of Respiratory and Critical Care Medicine 2003;167(6):841‐9. [CFGD Register: PI151d]
Rosenfeld M. Serum and lower respiratory tract tobramycin concentrations produced by inhaled tobramycin (TOBI) in young children with cystic fibrosis [abstract]. Pediatric Pulmonology 1999;Suppl 19:106‐8. [CFGD Register: PI151b]
Rosenfeld M, Borowitz D, Emerson J, Gibson R, McCoy K, McNamara S, et al. Serum pharmacokinetics and safety of inhaled tobramycin in very young CF patients [abstract]. Pediatric Pulmonology 1999;Suppl 19:262. [CFGD Register: PI151a]

Proesmans 2013 {published data only}

Proesmans M, Boulanger L, Vermeulen F, De Boeck K. Eradication of recent Pseudomonas aeruginosa isolation: TOBI versus colistin/ciprofloxacin [abstract]. Journal of Cystic Fibrosis 2008;7(S2):S64. [CFGD Register: PI208a]
Proesmans M, Boulanger L, Vermeulen F, De Boeck K. Eradication of recent Pseudomonas aeruginosa isolation: TOBI versus colistin/ciprofloxacin [abstract]. Pediatric Pulmonology 2009;44(S32):321, Abstract no: 311. [CFGD Register: PI208b; MEDLINE: 96296083]
Proesmans M, Boulanger L, Vermeulen F, De Boeck K. Eradication of recent pseudomonas aeruginosa infection: TOBI versus Colistineb®/ ciprofloxacin [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S26, Abstract no: 102. [CFGD Register: PI208c]
Proesmans M, Vermeulen F, Boulanger L, Verhaegen J, De Boeck K. Comparison of two treatment regimens for eradication of Pseudomonas aeruginosa infection in children with cystic fibrosis. Journal of Cystic Fibrosis 2013;12(1):29‐34. [CFGD Register: PI208d]

Ratjen 2010 {published data only}

Ratjen F, Munck A, Campello V. Inhaled tobramycin nebuliser solution for treatment of early Pseudomonas aeruginosa infection: first results from the Elite study [abstract]. Pediatric Pulmonlogy 2006;41(S29):318. [CFGD Register: PI197b]
Ratjen F, Munck A, Campello V. Safety of inhaled tobramycin nebuliser solution for treatment of early pseudomonas aeruginosa infection: first results from the ELITE study [abstract]. Journal of Cystic Fibrosis 2006;5 Suppl 1:S22. [CFGD Register: PI197a]
Ratjen F, Munck A, Kho P. Short and long‐term efficacy of inhaled tobramycin in early P. Aeruginosa infection: the ELITE study [abstract]. Pediatric Pulmonology 2008;43(S31):319. [CFGD Register: PI197d]
Ratjen F, Munck A, Kho P, Angyalosi G, for the ELITE Study Group. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax 2010;65(4):286‐91. [CFGD Register: PI197e]
Ratjen F, Stenglein S, Munck A. Inhaled tobramycin nebulizer solution for treatment of early Pseudomonas aeruginosa infection; the ELITE study [abstract]. Journal of Cystic Fibrosis 2008;7 Suppl 2:S26. [CFGD Register: PI197c]

Taccetti 2012 {published data only}

Cariani L, Defilippi G, Costantini D, Claut L, Clarizia G, D'accico M, et al. Semi‐automated rep‐pcr genotyping of pseudomonas aeruginosa in Italian CF patients in eradication therapy [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:348, Abstract no: 360. [CFGD Register: PI230c]
Dolce D, Cariani L, Ravenni N, Mergni G, Biffi A, Colombo C, et al. Anti‐P.aeruginosa antibodies and microbiological outcome in patients treated with early eradication therapy [abstract]. Pediatric Pulmonology 2013;48 Suppl 36:288, Abstract no: 231. [CENTRAL: 921692; CFGD Register: PI230i; CRS: 5500125000000403]
Taccetti G, Bianchini E, Zavataro L, Campana S, Defilippi G, Ravenni N, et al. Pseudomonas aeruginosa eradication in cystic fibrosis: preliminary data from a randomized multicenter study of two different early antibiotic treatment protocols [abstract]. Pediatric Pulmonology 2010;45(S33):337, Abstract no: 332. [CFGD Register: PI230d]
Taccetti G, Bianchini E, Zavataro L, Campana S, Defilippi G, Ravenni N, et al. Pseudomonas aeruginosa microbiological status and emergence of other pathogens after early eradication treatment in cystic fibrosis: a post‐trial follow‐up [abstract]. Pediatric Pulmonology 2011;46(S34):317, Abstract no: 292. [CFGD Register: PI230e]
Taccetti G, Bianchini E, Zavataro L, Campana S, Ravenni N, Boni V, et al. Early antibiotic treatment for Pseudomonas aeruginosa eradication in cystic fibrosis patients: a randomized multicenter study of two different protocols [abstract]. Pediatric Pulmonology 2009;44(S32):354, Abstract no: 406. [CFGD CF Register: PI230a; MEDLINE: 96296083]
Taccetti G, Bianchini E, Zavataro L, Costantini D, Galici V, Campana S, et al. Pseudomonas aeruginosa eradication in cystic fibrosis: final results of a randomized multicenter study of two different early antibiotic treatment protocols [abstract]. Pediatric Pulmonology 2011;46(S34):317, Abstract no: 291. [CFGD Register: PI230f]
Taccetti G, Cocchi P, Dolce D, Galici V, Mergni G, Gagliardini R, et al. Is early eradication treatment against P.aeruginosa associated with the emergence of other non‐fermenter gram negatives [abstract]. Pediatric Pulmonology 2013;48 Suppl 36:328, Abstract no: 338. [CENTRAL: 921671; CFGD Register: PI230h; CRS: 5500125000000398]
Taccetti G, Bianchini E, Cariani L, Buzzetti R, Costantini D, Trevisan F, et al. Early antibiotic treatment for Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing two different protocols. Thorax 2012;67(10):853‐9. [CFGD Register: PI230g]
Zavataro L, Taccetti G, Cariani L, Ravenni N, Braccini G, Bresci S, et al. Epidemiology of first/new Pseudomonas aeruginosa infection in cystic fibrosis patients [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S29, Abstract no: 110. [CFGD Register: PI230b]

Treggiari 2011 {published data only}

Anstead M, Lymp J, Khan U, Barbieri J, Langkamp M, Doring G, et al. Pseudomonas aeruginosa serology predicts response to treatment and re‐infection in the EPIC clinical study [abstract]. Pediatric Pulmonology 2011;46(S34):303, Abstract no: 254. [CFGD Register: PI202g]
Hamblett NM, Retsch‐Bogart GZ, Treggiari M, Kronmal RA, Khan U, Williams J, et al. Safety and efficacy of anti‐pseudomonal therapy for early eradication of Pseudomonas aeruginosa: the EPIC study [abstract]. Pediatric Pulmonology 2009;44(S32):183. [CFGD CF Register: PI202b; MEDLINE: 96296083]
Hoffman LR, Ramsey BW, Kulasekara HD, Retsch‐Bogart GZ, Wolter DJ, Pope CE, et al. Pseudomonas aeruginosa (PA) phenotypes associated with persistent early infection in CF patients in the EPIC Clinical Trial [abstract]. Pediatric Pulmonology 2012;47(S35):317, Abstract no: 266. [CFGD Register: PI202j]
Khan U, Mayer‐Hamblett N, Retsch‐Bogart G, Treggiari M, Ramsey B. Association between baseline pseudomonas aeruginosa positivity in EPIC clinical trial participants & prior antibiotic exposure [abstract]. Pediatric Pulmonology 2010;45(S33):335, Abstract no: 326. [CFGD Register: PI202f]
Mayer‐Hamblett N, Kronmal RA, Gibson RL, Rosenfeld M, Retsch‐Bogart G, Treggiari MM, et al. Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis. Pediatric Pulmonology 2012;47(2):125‐34. [CFGD Register: PI202i; DOI: 10.1002/ppul.21525]
Mayer‐Hamblett N, Rosenfeld M, Treggiari MM, Konstan MW, Retsch‐Bogart G, Morgan W, et al. Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis. Pediatric Pulmonology 2013;48(10):943‐53. [CENTRAL: 916577; CFGD Register: PI202k; CRS: 5500125000000727; PUBMED: 23818295]
Ramsey B. TOBI use in infants and children with early Pseudomonas Aeruginosa infection ‐ duration of effect and epic update [abstract]. Pediatric Pulmonology 2005;40(S28):146. [CFGD CF Register: PI202a]
Treggiari M, Retsch‐Bogart G, Mayer‐Hamblett N, Khan U, Kronmal R, Ramsey B, et al. Comparative efficacy and safety of four randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S54, Abstract no: 209. [CFGD Register: PI202e]
Treggiari M, Retsch‐Bogart GZ, Mayer‐Hamblett N, Kronmal R, Khan U, Williams J, et al. Early anti‐pseudomonal infection in children with CF: study population and conduct of the "EPIC" clinical trial [abstract]. Pediatric Pulmonology 2009;44(S32):316, Abstract no: 299. [CFGD CF Register: PI202c; MEDLINE: 96296083]
Treggiari MM, Retsch‐Bogart G, Mayer‐Hamblett N, Khan U, Kulich M, Kronmal R, et al. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Archives of Pediatrics and Adolescent Medicine 2011;165(9):847‐56. [CFGD Register: PI202h]
Treggiari MM, Rosenfeld M, Mayer‐Hamblett N, Retsch‐Bogart G, Gibson RL, Williams J, et al. Early anti‐pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study. Contempory Clinical Trials 2009;30(3):256‐68. [CFGD CF Register: PI202d; MEDLINE: 96296083]

Valerius 1991 {published data only}

Valerius NH, Koch C, Høiby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991;338(8769):725‐6. [CFGD Register: PI70b]
Valerius NH, Koch C, Høiby N. Prevention of chronic colonization with Pseudomonas aeruginosa in patients with CF by early treatment with ciprofloxacin and colistin aerosol inhalations [abstract]. Pediatric Pulmonology 1990;9(Supplement S5):248. [CFGD Register: PI70a]

Wiesemann 1998 {published data only}

Ratjen F, Steinkamp G, Döring G, Bauernfeind A, Wiesemann HG, Von Der Hardt H. Prevention of chronic pseudomonas aeruginosa infection by early inhalation therapy with tobramycin [abstract]. Pediatric Pulmonology 1994;Suppl 10:250. [CFGD Register: PI101a]
Wiesemann HG, Steinkamp G, Ratjen F, Baurnfeind A, Przyklenk B, Döring G, et al. Placebo‐controlled, double‐blind, randomised study of aerosolised tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Pediatric Pulmonology 1998;25(2):88‐92. [CFGD Register: PI101b]

Alothman 2002 {published data only}

Alothman GA, Alsaadi MM, Ho BL, Ho SL, Dupuis A, Corey M, et al. Evaluation of bronchial constriction in children with cystic fibrosis after inhaling two different preparations of tobramycin. Chest 2002;122(3):930‐4. [CENTRAL: 398028; CFGD Register: PI157b; CRS: 5500100000002196; PUBMED: 12226034]
Alothman GA, Coates AL, Corey M, Dupuis A, Ho SL, Ho BL, et al. In cystic fibrosis (CF) patients, does the inhalation of an intravenous tobramycin preparation result in more bronchospasm than a preservative free tobramycin preparation? [abstract]. Pediatric Pulmonology 2000;Suppl 20:298‐9. [CFGD Register: PI157a]

Alothman 2005 {published data only}

Alothman GA, Ho B, Alsaadi MM, Ho SL, O'Drowsky L, Louca E, et al. Bronchial constriction and inhaled colistin in cystic fibrosis. Chest 2005;127(2):522‐9. [CENTRAL: 502709; CFGD Register: PI190; CRS: 5500100000002670; PUBMED: 15705991]

Ballman 1998 {published data only}

Ballman M, Rabsch P, von der Hardt H. Long term follow up of changes in FEV1 and treatment intensity during Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Thorax 1998;53(9):732‐7.

Brett 1992 {published data only}

Brett MM, Simmonds EJ, Ghonheim ATM, Littlewood JM. The value of serum IgG titres against Pseudomonas aeruginosa in the management of early infection in cystic fibrosis. Archives of Disease in Childhood 1992;67(9):1086‐8. [CFGD Register: PI73]

Church 1997 {published data only}

Church DA, Kanga JF, Kuhn RJ, Rubio TT, Spohn WA, Stevens JC, et al. Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group. Pediatric Infectious Disease Journal 1997;16(1):97‐105. [CENTRAL: 135891; CFGD Register: PI115 ; CRS: 5500100000000803; PUBMED: 9002118]

Clancy 2013 {published data only}

Clancy JP, Dupont L, Konstan MW, Billings J, Fustik S, Goss CH, et al. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax 2013;68(9):818‐25. [CENTRAL: 876398; CFGD Register: PI207e // PI222c ; CRS: 5500050000000084; PUBMED: 23749840]
Clancy JP, Minic P, Dupont L, Goss CH, Quittner AL, Lymp JF, et al. Full analysis of data from two phase II blinded & placebo‐controlled studies of nebulized liposomal amikacin for inhalation (Arikace) in the treatment of CF patients with pseudomonas aeruginosa lung infection [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:299, Abstract no: 227. [CENTRAL: 848916; CFGD Register: PI207d // PI222b; CRS: 5500100000010628]
Dupont L, Minic P, Fustic S, Mazurek H, Solyom E, Feketova A, et al. A randomised placebo‐controlled study of nebulized liposomal amikacin (Arikace) in the treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection [abstract]. Journal of Cystic Fibrosis 2008;7 Suppl 2:S26. [CENTRAL: 790820; CFGD Register: PI207a; CRS: 5500100000003531]
Dupont LJ, Minic P, Fustik S, Mazurek H, Solyom E, Feketeova A, et al. A randomized placebo‐controlled study of nebulized liposomal amikacin (Arikace) in the treatment of cystic fibrosis patients with chronic Pseudomonas Aeruginosa lung infection [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:301. [CENTRAL: 790939; CFGD Register: PI207b; CRS: 5500100000003535]
Gupta R, Dupont L, Minin P, Fustik S, Mazurek H, Solyom E, et al. A randomized placebo‐controlled study of nebulized liposomal amikacin (Arikace) in the treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection (protocol TR02‐105) [abstract]. American Journal of Respiratory and Critical Care Medicine 2009;179:Abstract no: A1199. [CENTRAL: 790940; CFGD Register: PI207c; CRS: 5500100000003536]

Coates 2011 {published data only}

Coates AL, Denk O, Leung K, Ribeiro N, Chan J, Green M, et al. Higher tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis. Pediatric Pulmonology 2011;46(4):401‐8. [CENTRAL: 786190; CFGD Register: PI241b; CRS: 5500100000006333]
Denk O, Caotes AL, Keller M, Leung K, Green M, Chan J, et al. Lung delivery of a new tobramycin nebuliser solution (150mg/1.5ml) by an investigational eFlow® nebuliser is equivalent to TOBI® but in a fraction of time [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S66, Abstract no: 264. [CENTRAL: 794467; CFGD Register: PI241c; CRS: 5500100000003576]
Keller M, Coates AL, Griese M, Denk O, Schierholz J, Knoch M. In‐vivo data support equivalent therapeutic efficacy of a new tobramycin inhalation solution (150mg/1.5ml) administered by the eFlow® electronic nebuliser compared to TOBI® in the PARI LC PLUS® [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S22, Abstract no: 84. [CENTRAL: 794286; CFGD Register: PI241a; CRS: 5500100000003569]

Frederiksen 1997 {published data only}

Frederiksen B, Koch C, Høiby N. Antibiotic treatment of initial colonisation with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatric Pulmonology 1997;23(5):330‐5.

Geller 2007 {published data only}

Geller DE, Howenstine M, Conrad C, Smith J, Mulye S, Shrewsbury SB. A phase 1 study to assess the tolerability of a novel tobramycin powder for inhalation (TPI) formulation in cystic fibrosis subjects [abstract]. Pediatric Pulmonology 2004;38(Suppl 27):250. [CENTRAL: 507896; CFGD Register: PI187a ; CRS: 5500100000002694]
Geller DE, Konstan MW, Smith J, Noonberg SB, Conrad C. Novel tobramycin inhalation powder in cystic fibrosis subjects: Pharmacokinetics and safety. Pediatric Pulmonology 2007;42(4):307‐13. [CENTRAL: 587235; CFGD Register: PI187c ; CRS: 5500100000002919; PUBMED: 17352404]
Rodriguez CA, Shrewsbury SB, Potter SN, Nardella P, Geller DE. Single dose pharmacokinetics of tobramycin after administration of a novel dry powder formulation (TPI) in subjects with cystic fibrosis (cf) [abstract]. Pediatric Pulmonology 2004;38 Suppl 27:250. [CENTRAL: 526254; CFGD Register: PI187b ; CRS: 5500100000002754]

Gibson 2007 {published data only}

Gibson RL, Emerson J, Mayer‐Hamblett N, Burns JL, McNamara S, Accurso FJ, et al. Duration of treatment effect after tobramycin solution for inhalation in young children with cystic fibrosis. Pediatric Pulmonology 2007;42(7):610‐23.

Goss 2009 {published data only}

Goss CH, Clancy JP, Nick JA, Billings J, Rubenstein RC, Young KR, et al. A phase 2 blinded and placebo‐controlled study of nebulized liposomal amikacin (arikace) in the treatment of CF patients with Pseudomonas aeruginosa lung infection [abstract]. Pediatric Pulmonology 2009;44(S32):295. [CFGD CF Register: PI222]

Griese 2002 {published data only}

Griese M, Mueller I, Reinhardt D. Eradication of initial Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. European Journal of Medical Research 2002;7(2):79‐80.

Heinzl 2002 {published data only}

Heinzl B, Eber E, Oberwaldner B, Haas G, Zach M. Effects of inhaled gentamicin prophylaxis on acquisition of Pseudomonas aeruginosa in children with cystic fibrosis: a pilot study. Pediatric Pulmonology 2002;33(1):32‐7.

Kenny 2009 {published data only}

Kenny S, Hall V, Goldsmith C, Moore J, Rendall JC, Elborn JS. Eradication of Pseudomonas aeruginosa in adults with CF [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S39, Abstract no: 158. [CFGD CF Register: PI229a; MEDLINE: 96296083]
Kenny SL, Shaw TD, Downey DG, Moore JE, Rendall JC, Elborn JS. Eradication of Pseudomonas aeruginosa in adults with cystic fibrosis. BMJ Open Respiratory Research 2014;1:e000021.

Konstan 2010 {published data only}

Konstan MW, Geller DE, Brockhaus F, Zhang J, Angyalosi G. Tobramycin inhalation powder is effective and safe in the treatment of chronic pulmonary Pseudomonas aeruginosa (Pa) infection in patients with cystic fibrosi [abstract]. American Journal of Respiratory and Critical Care Medicine 2009;179:Abstract no: A1186. [CENTRAL: 744126; CFGD Register: PI227a; CRS: 5500100000003455]
Konstan MW, Geller DE, Minic P, Brockhaus F, Zhang J, Angyalosi G. Effective treatment of chronic Pseudomonas aeruginosa (Pa) infection with tobramycin inhalation powder in CF patients [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S27, Abstract no: 105. [CENTRAL: 744127; CFGD Register: PI227b; CRS: 5500100000003456]
Konstan MW, Geller DE, Minic P, Brockhaus F, Zhang J, Angyalosi G. Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: The EVOLVE trial. Pediatric Pulmonology 2010;46:230‐8. [CENTRAL: 867122; CFGD Register: PI227e; CRS: 5500100000011272; PUBMED: 20963831]
McColley S, Rietschel E, Brockhaus F, Angyalosi G, Higgins M. Safety of inhaled tobramycin in patients with cystic fibrosis [abstract]. Pediatric Pulmonology 2011;46 Suppl 34:344, Abstract no: 365. [CENTRAL: 848919; CFGD Register: PI227d // PI239h; CRS: 5500100000010634]
Novartis (NCT00125346). Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Subjects (EVOLVE). Http://clinicaltrials.gov/ct2/show/NCT001253462010. [CENTRAL: 867467; CFGD Register: PI227c ; CRS: 5500100000006168]

Latzin 2008 {published data only}

Latzin P, Fehling M, Bauernfeind A, Reinhardt D, Kappler M, Griese M. Efficacy and safety of intravenous meropenem and tobramycin versus ceftazidime and tobramycin in cystic fibrosis. Journal of Cystic Fibrosis 2008;7(2):142‐6. [CFGD Register: PI209]

Lenoir 2007 {published data only}

Lenoir G, Antypkin YG, Miano A, Moretti P, Zanda M, Varoli G, et al. Efficacy, safety, and local pharmacokinetics of highly concentrated nebulized tobramycin in patients with cystic fibrosis colonized with Pseudomonas aeruginosa. Paediatric Drugs 2007;9 Suppl:11‐20. [CFGD Register: Pi196c]
Lenoir G, Aryayev N, Varoli G, Monici Preti P. Aerosolized tobramycin in the treatment of patients with cystic fibrosis and pseudomonas aeruginosa infection [abstract]. Journal of Cystic Fibrosis 2006;5 Suppl 1:S42. [CFGD Register: PI196b]
Lenoir G, Aryayev N, Varoli G, Monici Preti P. Highly concentrated aerosolized tobramycin in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection [abstract]. European Respiratory Journal 2005;26 Suppl 49:620s. [CFGD Register: PI196a]

Littlewood 1985 {published data only}

Littlewood JM, Miller MG, Ghoneim AT, Ramsden CH. Nebulised colomycin for early pseudomonal colonisation in cystic fibrosis [letter]. Lancet 1985;1(8433):865.

Mainz 2014 {published data only}

Mainz JG, Schadlich K, Schien C, Michl R, Schelhorn‐Neise P, Koitschev A, et al. Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double‐blind, placebo‐controlled pilot study. Drug Design, Development and Therapy 2014;8:209‐17. [CENTRAL: 981442; CFGD Register: PI248b ; CRS: 5500125000000721; PUBMED: 24596456]
Mainz JG, Schien C, Schadlich K, Pfister W, Schelhorn‐Neise P, Koitschev A, et al. Sinonasal inhalation of tobramycin in cystic fibrosis patients with P. aeruginosa colonization of the upper airways ‐ results of a multicentric placebo‐controlled pilot study [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S21, Abstract no: 83. [CENTRAL: 848866; CFGD Register: PI248a ; CRS: 5500100000010543]

Mazurek 2012 {published data only}

Mazurek H, Chiron R, Pelikan L, Geidel C, Bolbas K, Antipkin Y, et al. Comparison of two inhaled tobramycin solutions in cystic fibrosis patients with chronic pseudomonas aeruginosa infection: results in different age subgroups [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S28, Abstract no: 111. [CENTRAL: 848929; CFGD Register: PI249b; CRS: 5500100000010714]
Mazurek H, Chiron R, Varoli G, Santoro D, Cicirello H, Antipkin Y. Efficacy on lung function and safety of multiple courses of tobramycin 300mg/4 ml nebuliser solution (Bramitob) in patients with cystic fibrosis and chronic pseudomonas aeruginosa infection: results from a 48‐week extension phase [abstract]. Journal of Cystic Fibrosis 2012;11 Suppl1:S74, Abstract no: 69. [CENTRAL: 867264; CFGD Register: PI249c; CRS: 5500100000011290]
Mazurek H, Lenoir G, Pelikan L, Geidel C, Bolbas K, Antipkin Y, et al. Head‐to‐head comparison of two inhaled tobramycin solutions in cystic fibrosis (CF) patients with chronic pseudomonas aeruginosa (Pa) infection [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S28, Abstract no: 110. [CENTRAL: 848928; CFGD Register: PI249a; CRS: 5500100000010713]

Oermann 2009 {published data only}

Oermann CM, McCoy KS, Retsch‐Bogart GZ, Gibson R, McKevitt M, Montgomery B. Antibiotic susceptibility in Pseudomonas Aeruginosa (PA) isolates following exposure to aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis [abstract]. Pediatric Pulmonology 2009;44(S32):309, Abstract no: 278. [CFGD CF Register: PI220a]
Oermann CM, McCoy KS, Retsch‐Bogart GZ, Gibson R, McKevitt M, Montgomery B. Effect of repeated exposure to aztreonam for inhalation solution (AZLI) therapy on cystic fibrosis respiratory pathogens [abstract]. Pediatric Pulmonology 2009;44(Suppl 32):335, Abstract no: 353. [CFGD Register: PI220d]
Oermann CM, McCoy KS, Retsch‐Bogart GZ, Gibson RL, Montgomery AB. Effect of multiple courses of Aztreonam Lysine for inhalation (AZLI) on FEV1 and weight in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA): analysis of 18 month data from CP‐AI‐006 [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S28, Abstract no: 107. [CFGD CF Register: PI220c]
Oermann CM, McCoy KS, Retsch‐Bogart GZ, Gibson RL, Quittner AL, Montgomery AB. Adherence over multiple courses of Aztreonam for inhalation (AZLI): effect on disease‐ related endpoints in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S28, Abstract no: 109. [CFGD CF Register: PI220b]
Oermann CM, Retsch‐Bogart GZ, Quittner AL, Gibson RL, McCoy KS, Montgomery AB, et al. An 18‐month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatric Pulmonology 2010;45(11):1121‐34. [CFGD Register: PI220e]
Quitnner AL, Henig NR, Lewis S, Derchak PA, McCoy KS, Oermann CM, et al. Effects of chronic intermittant aztreonam for inhalation solution (AZLI) on health‐related quality of life (HRQOL) in persons with cystic fibrosis (CF) and P. aeruginosa [abstract]. Pediatric Pulmonology 2011;46 Suppl 34:299, Abstract no: 240. [CENTRAL: 867260; CFGD Register: PI220f/PI213j; CRS: 5500100000011261]

Postnikov 2000 {published data only}

Postnikov SS, Semykin SYU, Kapranov NI, Perederko LV, Polikarpova SV, Khamidullina KF. Evaluation of pefloxacin efficacy and tolerability in the treatment and prophylaxis of severe infections at the children with mucoviscidosis and aplastic anaemia. Antibiotiki i Khimioterapiia 2000;45(8):25‐30. [CFGD Register: PI171]

Postnikov 2007 {published data only}

Postnikov SS, Semykin SY, Polikarpova SV, Dubovik LG, Gracheva LA, Sagatelyan. A prospective trial on the efficacy and tolerability of twice‐daily dosing (TDD) versus once‐daily dosing (ODD) amikacin in cystic fibrosis patients [abstract]. Journal of Cystic Fibrosis 2007;6 Suppl 1:S34. [CFGD CF Register: PI204]

Prayle 2013 {published data only}

Prayle A, Jain K, Watson A, Smyth AR. Are morning doses of intravenous tobramycin less nephrotoxic than evening? Evidence from urinary biomarkers in the critic study [abstract]. Pediatric Pulmonology 2013;48 Suppl 36:299, Abstract no: 261. [CENTRAL: 980338; CFGD Register: CO55 ; CRS: 5500125000000420]

Ramsey 1999 {published data only}

Birnbaum HG, Greenberg P, Finkelstein S, Berndt E, Otto KL, Montgomery AB, et al. Economic analysis of hospitalization and home IV anti‐pseudomonal antibiotic use in CF patients on tobramycin solution for inhalation (TOBI®) [abstract]. Pediatric Pulmonology 1998;Suppl 17:273. [CENTRAL: 792738; CRS: 5500100000003553]
Bowman CM. The long‐term use of inhaled tobramycin in patients with cystic fibrosis. Journal of Cystic Fibrosis 2002;1 Suppl 2(Suppl 2):S194‐8. [CENTRAL: 451888; CFGD Register: PI120cc ; CRS: 5500100000002389]
Burns JL, Van Dalfsen JM, Shawar RM, Otto KL, Garber RL, Quan JM, et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. Journal of Infectious Diseases 1999;179(5):1190‐6. [CENTRAL: 161606; CRS: 5500100000000895; PUBMED: 10191222]
Casey S, Ramsey B, Borowitz D. Nutritional benefits of chronic intermittent Pseudomonas aeruginosa suppression with tobramycin solution for inhalation in adolescents [abstract]. 13th International Cystic Fibrosis Congress; 2000 June 4‐8; Stockholm, Sweden. 2000:172. [CENTRAL: 302945; CRS: 5500100000001685]
Enger C, Rothman K, Kylstra JW. Mortality rates during 2 years of treatment with intermittent inhaled tobramycin (TOBI) in CF [abstract]. Pediatric Pulmonology 1999;Suppl 19:339‐40. [CENTRAL: 291292; CRS: 5500100000001353]
Fiel SB. Long term effect of tobramycin solution for inhalation on reduction of hospitalization of CF patients [abstract]. European Respiratory Journal 2000;16(Suppl 31):1545. [CENTRAL: 415647; CRS: 5500100000002265]
Fiel SB. Long term effect of tobramycin solution for inhalation on reduction of hospitalization of CF patients [abstract]. European Respiratory Journal 2000;16(Suppl 31):1545. [CENTRAL: 415647; CFGD Register: PI120dd ; CRS: 5500100000002265]
Geller DE, Pitlick WH, Nardella PA, Tracewell WG, Ramsey BW. Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 2002;122(1):219‐26. [ CFGD Register: PI120bb ; CENTRAL: 404033; CRS: 5500100000002214]
Graff GR, Gordon DC, Van Dalfsen JM, Burns JL. Epidemiology of Stenotrophomonas maltophilia culture in cystic fibrosis (CF) patients during the tobramycin solution for inhalation (TOBI®) study [abstract]. Pediatric Pulmonology 2000;Suppl 20:283. [CENTRAL: 793580; CRS: 5500100000003564]
Hazinski TA. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Journal of Pediatrics 1999;135(1):130. [CENTRAL: 165714; CRS: 5500100000000909; EMBASE: 1999019576; PUBMED: 10428654]
Konstan MW, VanDevanter DR. Peripheral white blood cell count as a surrogate marker for progression of lung disease in cystic fibrosis [abstract]. Pediatric Pulmonology 2001;Suppl 22:305. [CENTRAL: 362193; CRS: 5500100000001991]
Kylstra JW, Bowman CM, Meyer U, Montgomery AB, Schaeffler B, Stewart P, et al. Who benefits more? An age‐stratified analysis of lung function and weight gain in CF patients using inhaled tobramycin [abstract]. Netherlands Journal of Medicine 1999;54(Suppl):S83. [CENTRAL: 291415; CRS: 5500100000001449]
LeLorier J, Perreault S, Birnbaum H, Greenberg P, Sheehy O. Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis. Clinical Therapeutics 2000;22(1):140‐51. [CENTRAL: 275378; CRS: 5500100000001232; PUBMED: 10688397]
LiPuma JJ. Microbiological and immunologic considerations with aerosolized drug delivery. Chest 2001;120(3 Suppl):118S‐23S. [CENTRAL: 356379; CRS: 5500100000001971; PUBMED: 11555566]
MacLeod DL, Nelson LE, Shawar RM, Lin BB, Lockwood LG, Dirk JE, et al. Aminoglycoside‐resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long‐term, intermittent, inhaled tobramycin treatment. Journal of Infectious Diseases 2000;181(3):1180‐4. [CENTRAL: 302968; CRS: 5500100000001702]
Moss R, Kylstra JW, Montgomery AB, Gibson R. Who benefits more? An analysis of FEV1 and weight in adolescent (age 13‐<18) CF patients using inhaled tobramycin (TOBI) [abstract]. Pediatric Pulmonology 1999;Suppl 19:243. [CENTRAL: 291469; CRS: 5500100000001497]
Moss RB. Administration of aerosolized antibiotics in cystic fibrosis patients. Chest 2001;120(3 Suppl):107S‐13S. [CENTRAL: 368291; CRS: 5500100000002023]
Moss RB. Long‐term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest 2002;121(1):55‐63. [CENTRAL: 377132; CRS: 5500100000002049; PUBMED: 11796432]
Nickerson B, Montgomery AB, Kylstra JW, Ramsey BW. Safety and effectiveness of 2 years of treatment with intermittent inhaled tobramycin in CF patients [abstract]. Pediatric Pulmonology 1999;Suppl 19:243‐4. [CENTRAL: 291479; CRS: 5500100000001506]
Otto KL, Montgomery AB, Lin A, Ramsey BW. Seasonality of hospitalization for pulmonary exacerbations and lower respiratory tract infections in Phase III tobramycin solution for inhalation (TOBI®) trials [abstract]. Pediatric Pulmonology 1998;Suppl 17:273. [CENTRAL: 795752; CRS: 5500100000003601]
Quan JM, Vasiljev M, Schaeffler B, Phelps C, Burrington C, Meyer U. Treatment for exacerbation only does not arrest progressive lung function decline in CF [abstract]. Netherlands Journal of Medicine 1999;54(Suppl):S84. [CENTRAL: 291523; CRS: 5500100000001545]
Quittner A, Gordon D, Yu X. Convergence of quality of life assessments and clinical outcomes in patients enrolled in the tobramycin solution for inhalation (TSI) trials [abstract]. 24th European Cystic Fibrosis Conference; 2001 June 6‐9; Vienna, Austria. 2001:P326. [CENTRAL: 614345; CRS: 5500100000003153]
Quittner AL, Buu A. Effects of tobramycin solution for inhalation on global ratings of quality of life in patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatric Pulmonology 2002;33(4):269‐76. [CENTRAL: 379174; CRS: 5500100000002059; PUBMED: 11921456]
Quittner AL, Buu A, Gordon D. Longitudinal changes in global ratings of quality of life for patients in the tobramycin solution for inhalation (TSI) trials [abstract]. Pediatric Pulmonology 2001;Suppl 22:349. [CENTRAL: 362214; CRS: 5500100000002002]
Ramsey B, Burns J, Smith A. Safety and efficacy of Tobramycin Solution for Inhalation in patients with cystic fibrosis: The results of two phase III placebo controlled clinical trials [abstract]. Pediatric Pulmonology 1997;Suppl 14:137‐8. [CENTRAL: 385760; CRS: 5500100000002121]
Ramsey BW, Bowman MC, Montgomery AB, Smith AR, TOBIStudy G. Design of phase 3 aerosolized tobramycin studies for chronic intermittent therapy [abstract]. 21st European Cystic Fibrosis Conference; 1997 June 1‐6; Davos, Switzerland. 1997:144. [CENTRAL: 291527; CRS: 5500100000001548]
Ramsey BW, Bowman MC, Vasiljev‐KM, Smith AR, TOBIStudy G. Results of phase 3 aerosolized tobramycin studies for chronic intermittent therapy [abstract]. 21st European Cystic Fibrosis Conference; 1997 June 1‐6; Davos, Switzerland. 1997:144. [CENTRAL: 291528; CRS: 5500100000001549]
Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams Warren J, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. cystic fibrosis Inhaled Tobramycin Study Group. New England Journal of Medicine 1999;340(1):23‐30. [CENTRAL: 158508; CRS: 5500100000000883; PUBMED: 9878641]
Rosenfeld M, Emerson J, Williams‐Warren J, Pepe M, Smith A, Montgomery AB, et al. Defining a pulmonary exacerbation in cystic fibrosis. Journal of Pediatrics 2001;139(3):359‐65. [CENTRAL: 384105; CRS: 5500100000002077; PUBMED: 11562614]
Taylor CJ. Nebulised high dose Tobramycin (TOBI) in adolescents with cystic fibrosis [abstract]. Pediatric Pulmonology 2001;Suppl 22:291. [CENTRAL: 362226; CRS: 5500100000002008]
VanDevanter D, Hou K, Yu X. Effect of tobramycin solution for inhalation (TOBI®) on long term rates of lung function decline in Pseudomonas aeruginosa infected cystic fibrosis (CF) patients with mild to moderate lung disease [abstract]. Pediatric Pulmonology 2000;Suppl 20:298. [CENTRAL: 793150; CRS: 5500100000003557]
VanDevanter D, Yu X, Konstan MW. Effect of tobramycin solution for inhalation on circulating white blood cell counts in exacerbating and stable CF patients [abstract]. 24th European Cystic Fibrosis Conference; 2001 June 6‐9; Vienna, Austria. 2001:P172. [CENTRAL: 354463; CRS: 5500100000001964]

Ratjen 2001a {published data only}

Ratjen F, Döring G, Nikolaizik WH. Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet 2001;358(9286):983‐4.

Retsch‐Bogart 2008 {published data only}

Burns JL, Stapp J, Lofland D, AIPhase 2SG. Microbiology results from a phase 2 clinical study of aztreonam lysinate for inhalation (AI): a new inhaled antibiotic to treat CF patients with Pseudomonas aeruginosa (PA) [abstract]. Journal of Cystic Fibrosis 2005;4 Suppl:S55. [CENTRAL: 548338; CFGD Register: PI211a ; CRS: 5500100000002786]
Retsch‐Bogart GZ, Burns JL, Otto KL, Liou TG, McCoy K, Oermann C, et al. A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatric Pulmonology 2008;43(1):47‐58. [CENTRAL: 628521; CFGD Register: PI211c; CRS: 5500100000003193; PUBMED: 18041081]
Retsch‐Bogart GZ, Gibson RL, AIPhase 2SG. A phase 2 study of aztreonam lysinate for inhalation to treat cystic fibrosis patients with Pseudomonas aeruginosa infection [abstract]. American Thoracic Society International Conference; 2005 May 20‐25; San Diego, USA. 2005:A576. [CENTRAL: 592963; CFGD Register: PI211b ; CRS: 5500100000002930]
Retsch‐Bogart GZ, McCoy KS, Gibson RL, Oermann CM. Sustained improvement in pulmonary function following a 28‐day course of 75mg azli tid therapy [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:320. [CENTRAL: 675920; CFGD Register: PI211d // PI213b; CRS: 5500100000003286]

Retsch‐Bogart 2009 {published data only}

McCoy K, Retsch‐Bogart G, Gibson RL, Oermann C, Braff M, Montgomery AB. Investigation of susceptibility breakpoints for inhaled antibiotic therapies in cystic fibrosis [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:341, Abstract no: 340. [CENTRAL: 848913; CFGD Register: PI212g // PI213i ; CRS: 5500100000010623]
McCoy KS, Retsch‐Boagrt GZ, Gibson RL, Oermann CM, McKevitt M, Montgomery AB. Efficacy of Aztreonam Lysine for inhalation (AZLI) in patients with cystic fibrosis and drug resistant P. aeruginosa (DRPA) [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S28. [CENTRAL: 744120; CFGD Register: PI212e // PI213e ; CRS: 5500100000003449]
McCoy KS, Retsch‐Bogart GZ, Gibson R, Oermann C, Braff MH, Montgomery AB. Relevance of established susceptibility breakpoints to clinical efficacy of inhaled antibiotic therapies in cystic fibrosis [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:351. [CENTRAL: 677646; CFGD Register: PI212b // PI213c; CRS: 5500100000003289]
Plosker GL. Aztreonam lysine for inhalation solution: in cystic fibrosis. Drugs 2010;70(14):1843‐55. [CENTRAL: 848912; CFGD Register: PI212f // PI213h ; CRS: 5500100000010622]
Quittner AL, Henig NR, Lewis S, Derchak PA, McCoy KS, Oermann CM, et al. Effects of chronic intermittent aztreonam for inhalation solution (AZLI) on health‐related quality of life (HRQOL) in persons with cystic fibrosis (CF) and P. aeruginosa [abstract]. Pediatric Pulmonology 2011;46 Suppl 34:299, Abstract no: 240. [CENTRAL: 867260; CFGD Register: PI213j // PI220f; CRS: 5500100000011261]
Quittner AL, Retsch‐Bogart GZ, McCoy KS, Oermann CM, Gibson R, Lewis S, et al. Effect of a 28‐day course of aztreonam for inhalation solution (AZLI) on responses to individual CFQ‐R respiratory symptoms score questions among patients with CF [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:305, Abstract no: 266. [CENTRAL: 744128; CFGD Register: PI213f ; CRS: 5500100000003457]
Retsch‐Bogart GZ, McCoy KS, Gibson RL, Oermann C, Montgomery AB. Source of improvements in lung function in patients with cystic fibrosis (CF) following treatment with aztreonam lysine for inhalation (AZLI) [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:320. [CENTRAL: 744116; CFGD Register: PI213d; CRS: 5500100000003445]
Retsch‐Bogart GZ, McCoy KS, Gibson RL, Oermann CM. Sustained improvement in pulmonary function following a 28‐day course of 75mg azli tid therapy [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:320. [CENTRAL: 675920; CFGD Register: PI211d // PI213b; CRS: 5500100000003286]
Retsch‐Bogart GZ, Montgomery B, Gibson R, McCoy K, Oermann CM, Cooper P. Phase 3 trial (AIR‐CF 1) measuring improvement in respiratory symptoms in patients with cystic fibrosis (CF) following treatment with aztreonam lysine for inhalation [abstract]. Pediatric Pulmonology 2007;42 Suppl 30:310. [CENTRAL: 623759; CFGD Register: PI213a; CRS: 5500100000003182]
Retsch‐Bogart GZ, Quittner AL, Gibson RL, Oermann CM, McCoy KS, Montgomery AB, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009;135(5):1223‐32. [CENTRAL: 698536; CFGD Register: PI213g ; CRS: 5500100000010621]

Rietschel 2009 {published data only}

Rietschel E, Posselt HG, Heuer HE, Merkel N, Staab D. Pharmacokinetics of tobramycin (TOBI) after 4 and 8 weeks of continuous once daily or twice daily inhalation [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S27, Abstract no: 106. [CENTRAL: 795021; CFGD Register: PI232a; CRS: 5500100000003587]
Rietschel E, Staab D, Merkel N, van Konigsbruggen S, Posselt H. Pharmacokinetics of continuous treatment with O.D. or B.I.D inhalation of tobramycin (TOBI™) via Pari Eflow™ Rapid [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:320, Abstract no: 283. [CENTRAL: 849031; CFGD Register: PI232c; CRS: 5500100000010629]
Rietschel E, Staab D, von Konigsbruggen S, Merkel N, Heuer HE, Posselt HG. Pharmacokinetics of continuous treatment with o.d. or b.i.d. inhalation of tobramycin (TOBITM) [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S23, Abstract 106. [CENTRAL: 795018; CFGD Register: PI232b; CRS: 5500100000003586]

Schaad 1997 {published data only}

Schaad UB, Wedgwood J, Ruedeberg A, Kraemer R, Hampel B. Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis. Pediatric Infectious Diseases Journal 1997;16(1):106‐11. [CFGD Register: PI116]

Schelstraete 2010 {published data only}

Schelstraete P, Deschaght P, Van Daele S, Haerynck F, Van Simaey L. Genotype based evaluation of eradication treatment of new P. aeruginosa infections in CF patients [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S39, Abstract no: 156. [CFGD CF Register: PI228; MEDLINE: 96296083]
Schelstraete P, Deschaght P, Van Simaey L, Van Daele S, Haerynck F, Vaneechoutte M, et al. Genotype based evaluation of Pseudomonas aeruginosa eradication treatment success in cystic fibrosis patients. Journal of Cystic Fibrosis 2010;9(2):99‐103. [CFGD Register: PI228]

Schuster 2013 {published data only}

Goldman M, Schuster A, Halliburn C, Döring G, The FSG. A randomised, open label phase 3 study to evaluate the efficacy and safety of a dry powder formulation of inhaled colistimethate sodium (Colobreathe®) versus tobramycin nebuliser solution (TNS) in cystic fibrosis subjects with chronic Pseudomonas aeruginosa lung infection [abstract]. Journal of Cystic Fibrosis 2012;11, Suppl 1:S12, Abstract no: WS5.5. [CENTRAL: 848917; CFGD Register: PI214b ; CRS: 5500100000010630]
Goldman MH, Pitt T. Lack of emergence of antimicrobial resistance of Pseudomonas Aeruginosa after six months inhalation of dry powder colistimethate [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:331. [CFGD Register: PI214a]
Goldman MH, Shuster A, Haliburn C, Doring G. A randomised, open label phase 3 study to evaluate the efficacy and safety of a dry powder formulation of colistimethate sodium (Colobreathe®) versus tobramycin nebuliser solution (TNS) in cystic fibrosis subjectes with chronic Pseudomonas aeruginosa lung infection [abstract]. Pediatric Pulmonology 2012;47(S35):353, Abstract no: 363. [CENTRAL: 849030; CFGD Register: PI214c ; CRS: 5500100000010631]
Goldman MH, Werner T, Schuster A. Does persistence with inhaled dry powder antibiotic treatment improve tolerability? [abstract]. Pediatric Pulmonology 2013;48 Suppl 36:347, Abstract no: 389. [CENTRAL: 921669; CFGD Register: PI214f; CRS: 5500125000000396]
Schuster A, Haliburn C, Doring G, Goldman MH, FSG. Online Data Supplement to 'Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised' [online] study. Thorax 2013;68(4):344‐350 Online. [CENTRAL: 867327; CFGD Register: PI214e; CRS: 5500100000011299]
Schuster A, Haliburn C, Doring G, Goldman MH, FSG. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax 2013;68(4):344‐50. [CENTRAL: 864435; CFGD Register: PI214d; CRS: 5500100000011298; PUBMED: 23135343]

Steinkamp 1989 {published data only}

Steinkamp G, Tummler B, Malkotte R, Von der Hardt H. Treatment of Pseudomonas aeruginosa colonisation in cystic fibrosis. Archives of Disease in Childhood 1989;64(7):1022‐8.

Steinkamp 2007 {published data only}

Steinkamp G, Schmitt‐Grohe S, Doring G, Stabb D, Schubert R, Zielen S. Once weekly azithromycin in cystic fibrosis: a double‐blind, randomised trial in patients with chronic Pseudomonas aeruginosa infection [abstract]. Pediatric Pulmonology 2007;42(S30):300. [CFGD Register: MA19b]
Steinkamp G, Schmitt‐Grohe S, Doring G, Worlitzsch D, Staab D, Schubert R, et al. Clinical and immunomodulatory effects of once weekly azithromycin treatment in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa [abstract]. Journal of Cystic Fibrosis 2006;5 Suppl 1:S25. [CFGD Register: MA19a]

Taccetti 2005 {published data only}

Taccetti G, Campana S, Festini F, Mascherini M, Doring G. Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients. European Respiratory Journal 2005;26(3):1‐4.

Tramper‐Stranders 2009 {published data only}

Tramper‐Stranders G, Wolfs TFW, van Aalderen W, Kouwenberg J, Nagelkerke A, van der Ent CK. Prevention of initial P. aeruginosa infection in children with cystic fibrosis: a multi‐centre double‐blind randomised controlled trial [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S37, Abstract no: 148. [CFGD Register: PI231a; MEDLINE: 96296083]
Tramper‐Stranders GA, Wolfs TF, van Haren Noman S, van Aalderen WM, Nagelkerke AF, Nuijsink M, et al. Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Thorax 2010;65(10):915‐20. [CENTRAL: 761942; CFGD Register: PI231b; CRS: 5500125000000359; PUBMED: 20729233]

Trapnell 2012 {published data only}

McColley SA, Trapnell B, Kissner D, McKevitt M, Montgomery B, Rosen J, et al. Fosfomycin/tobramycin for inhalation (FTI): microbiological results of a phase 2 placebo‐controlled trial in patients with cystic fibrosis and pseudomonas aeruginosa [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:338, Abstract no: 334. [CENTRAL: 848865; CFGD Register: PI247c; CRS: 5500100000010542]
Trapnell BC, Kissner D, Montgomery AB, Newcomb T, Geller D. Fosfomycin/tobramycin for inhalation FTI): safety results of a phase 2 placebo‐controlled trial in patients with cystic fibrosis and pseudomonas aeruginosa [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:302, Abstract no: 234. [CENTRAL: 848864; CFGD Register: PI247b; CRS: 5500100000010541]
Trapnell BC, McColley SA, Kissner DG, Rolfe MW, Rosen JM, McKevitt M, et al. Fosfomycin/tobramycin for inhalation in patients with cystic fibrosis with pseudomonas airway infection. American Journal of Respiratory and Critical Care Medicine 2012;185(2):171‐8. [CENTRAL: 814492; CFGD Register: PI247d; CRS: 5500100000010632]
Trapnell BC, Rolfe M, McColley S, Montgomery AB, Moorehead L, Geller D. Fosfomycon/tobramycin for inhalation (FTI): efficacy results of a phase 2 placebo‐controlled trial in patients with cystic fibrosis and pseudomonas aeruginosa [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:302, Abstract no: 233. [CENTRAL: 848927; CFGD Register: PI247a; CRS: 5500100000010712]

Vazquez 1993 {published data only}

Vazquez C, Municio M, Corera M, Gaztelurrutia L, Sojo A, Vitoria JC. Early treatment of Pseudomonas aeruginosa colonisation in cystic fibrosis. Acta Paediatrica Scandanavia 1993;82(3):308‐9.

Wainwright 2011a {published data only}

Byrnes CA, Vidmar S, Cheney JL, Carlin JB, Armstrong DS, Cooper PJ, et al. Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age. Thorax 2013;68(7):643‐51. [CENTRAL: 904924; CFGD Register: PE167i; CRS: 5500125000000477; PUBMED: 23345574]
Cheney J, Vidmar S, Grimwood K, Carlin JB, Wainwright C, on behalfofACFBALSG. Interim outcomes of a Pseudomonas aeruginosa (Pa) eradication protocol in young children in the Australian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) Study [abstract]. Journal of Cystic Fibrosis 2009;8(Suppl 2):S39, Abstract no:157. [CFGD Register: PE167c]
Cheney J, Wainwright C, ACFBAL SG. Trials, tribulations and triumphs of a cystic fibrosis study ‐ a behind the scenes look at the workings of an international multi‐centre study [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S118, Abstract no: 452. [CENTRAL: 790042; CFGD Register: PE167g; CRS: 5500125000000092]
Wainwright C, Carlin J, Cooper P, Byrnes C, Martin J, Grimwood K, et al. Australasian cystic fibrosis BAL study interim analysis [abstract]. Pediatric Pulmonology 2006;41 Suppl 29:317. [CFGD Register: PE167a]
Wainwright CE, Carlin J, Cooper P, Byrnes C, Whitehead B, Martin J, et al. Early infection with pseudomonas aeruginosa can be cleared in young children with cystic fibrosis [abstract]. Pediatric Pulmonology 2002;34 Suppl 24:300‐1. [CFGD Register: PI167d]
Wainwright CE, Kidd TJ, Ramsey KA, Bell SC, Grimwood K. Australasian CF bronchoalveolar lavage (ACFBAL) study: P.Aeruginosa (PA) genotypes in pre‐school CF children [abstract]. Pediatric Pulmonology 2011;46 Suppl 34:320, Abstract no: 299. [CENTRAL: 874662; CFGD Register: PE167h; CRS: 5500125000000093]
Wainwright CE, Vidmar S, Armstrong DS, Byrnes CA, Carlin JB, Cheney J, et al. Effect of bronchoalveolar lavage‐directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial. JAMA 2011;306(2):163‐71. [CFGD Register: PI167e]
Wainwright CE, Vidmar S, Armstrong DS, Byrnes CA, Carlin JB, Cheney J, et al. Online Supplement to 'Effect of bronchoalveolar lavage‐directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial' [online]. JAMA 2011;306(2):163‐171 Online. [CENTRAL: 788878; CFGD Register: PE167f; CRS: 5500100000011126; PUBMED: 21750293]
Wainwright CE,  Grimwood K,  Carlin JB,  Vidmar S,  Cooper PJ,  Francis PW, et al. Safety of bronchoalveolar lavage in young children with cystic fibrosis. Pediatric Pulmonology 2008;43(10):965‐72. [CFGD Register: PI167b]

Wainwright 2011b {published data only}

Wainwright CE, Quittner AL, Geller DE, Nakamura C, Wooldridge JL, Gibson RL, et al. Aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis, mild lung impairment, and P. aeruginosa. Journal of Cystic Fibrosis 2011;10(4):234‐42. [CENTRAL: 801029; CFGD Register: PI273 ; CRS: 5500100000011273; PUBMED: 21441078]

Noah 2010 {published data only}

Noah T, Ivins S, Abode K, Harris W, Henry M, Leigh M. Comparison of antibiotics for early pseudomonas infection in CF: interim data analysis [abstract]. Pediatric Pulmonology 2007;42(S30):332. [CFGD Register: PI205a]
Noah TL, Ivins SS, Abode KA, Stewart PW, Michelson PH, Harris WT, et al. Inhaled versus systemic antibiotics and airway inflammation in children with cystic fibrosis and Pseudomonas. Pediatric Pulmonology 2010;45(3):281‐90. [CFGD Register: PI205b]

TORPEDO Trial {published data only}

Langton Hewer S. TORPEDO‐CF. http://www.controlled‐trials.com/ISRCTN02734162/torpedo‐cf accessed 10 October 2011. [ISRCTN02734162]

Abman 1991

Abman SH, Ogle JW, et al. Early bacteriologic, immunologic and clinical courses of young infants with cystic fibrosis identified by neonatal screening. Journal of Pediatrics 1991;119(2):211‐7.

Anstead 2013

Anstead M, Heltshe S, Khan U, Barbieri JT, Langkamp M, Doring G, et al. Pseudomonas aeruginosa serology and risk for re‐isolation in the EPIC trial. Journal of Cystic Fibrosis 2013;12(2):147‐53.

Armstrong 1996

Armstrong D, Grimwood K, Carlin J, Carzino R, Olinsky A, Phelan P. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatric Pulmonology 1996;21(5):267‐75.

Burns 2001

Burns JL, Gibson RL, McNamara S, Yim D, Emerson J, Rosenfeld M, et al. Longitudanal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. Journal of Infectious Diseases 2001;183(3):444‐52.

Ciofu 2012

Ciofu O, Mandsberg LF, Wang H, Hoiby N. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections. FEMS Immunology and Medical Microbiology 2012;65(2):215‐25.

Douglas 2009

Douglas TA, Brennan S, Gard S, Berry L, Gangell C, Stick SM, et al. Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis. European Respiratory Journal 2009;33(2):305‐11.

Döring 2000

Döring G, Conway S, Heijerman H, Hodson M, Høiby N, Smyth A, et al. Antibiotic therapy against Pseudomonas aeruginosa: a European consensus. European Respiratory Journal 2000;16(4):749‐67.

Döring 2012

Döring G, Flume P, Heijerman H, Elborn JS. Treatment of lung infection in patients with cystic fibrosis: Current and future strategies. Journal of Cystic Fibrosis 2012;11(6):461‐79.

Emerson 2002

Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatric Pulmonology 2002;34(2):91‐100.

FitzSimmons 1993

FitzSimmons SC. The changing epidemiology of cystic fibrosis. Journal of Pediatrics 1993;122(1):1‐9.

Fitzsimmons 1996

Fitzsimmons S. The Cystic Fibrosis Foundation Patient Registry Report 1996. Pediatric Pulmonology 1996;Suppl 21:267‐75.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60.

Higgins 2011

Higgins JPT, Altman DG. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Hilliard 2007

Hilliard TN, Sukhani S, Francis J, Madden N, Rosenthal M, Balfour‐Lynn I, et al. Bronchoscopy following diagnosis with cystic fibrosis. Archives of Disease in Childhood 2007;92(10):989‐9.

Hudson 1993

Hudson V, Wielinski C, Regelmann W. Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. Journal of Pediatrics 1993;122(6):854‐60.

Iacocca 1963

Iacocca VF, Sibinga M, Barbero G. Respiratory Tract Bacteriology in Cystic Fibrosis. American Journal of Disease in Childhood 1963;106(3):115‐24.

Johansen 2013

Johansen HK, Gøtzsche PC. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD001399.pub3]

Kerem 1990

Kerem E, Corey M, Stein R, Gold R, Levison H. Risk factors for Pseudomonas aeruginosa colonisation in cystic fibrosis patients. Pediatric Infectious Disease Journal 1990;9(7):494‐8.

Kosorok 2001

Kosorok MR, Zeng L, West SE, Rock MJ, Splaingard ML, Laxova A, et al. Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition. Pediatric Pulmonology 2001;32(4):277‐87.

Lee 2003

Lee TWR, Brownlee KG, Conway SP, Denton M, Littlewood JM. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. Journal of Cystic Fibrosis 2003;2(1):29‐34.

Lee 2004

Lee TW, Brownlee KG, Denton M, Littlewood JM, Conway SP. Reduction in prevalence of chronic Pseudomonas aeruginosa infection at a regional pediatric cystic fibrosis center. Pediatric Pulmonology 2004;37(2):104‐10.

Lee 2009

Lee TWR. Eradication of early Pseudomonas infection in cystic fibrosis. Chronic Respiratory Disease 2009;6(2):99‐107.

Montori 2005

Montori VM, Devereaux PJ, Adhikari NKJ, Burns KEA, Eggert CH, Briel M, et al. Randomized Trials Stopped Early for Benefit: A Systematic Review. JAMA 2005;294(17):2203‐9.

Muhlebach 1999

Muhlebach M, Stewart P, Leigh M, Noah T. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. American Journal of Respiratory & Critical Care Medicine 1999;160(1):186‐91.

Munck 2001

Munck A, Bonacorsi S, Mariani‐Kurkdjian P, Lebourgeois M, Gerardin M, Brahimi N, et al. Genotypic characterisation of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonisation. Pediatric Pulmonology 2001;32(4):288‐92.

Nixon 2001

Nixon GM, Armstrong DS, Carzino R, Carlin JB, Olinsky A, Robertson CF, et al. Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. Journal of Pediatrics 2001;138(5):699‐704.

Pamukcu 1995

Pamukcu A, Bush A, Buchdal R. Effects of Pseudomonas aeruginosa colonisation on lung function and anthropomorphic variables in children with cystic fibrosis. Pediatric Pulmonology 1995;19(1):10‐5.

Parad 1999

Parad RB, Gerard CJ, Zurakowski D, Nichols DP, Pier GB. Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. Infection & Immunity 1999;67(9):4744‐50.

Ramsey 1996

Ramsey B. Drug therapy: Management of pulmonary disease in patients with cystic fibrosis. New England Journal of Medicine 1996;335(3):179‐88.

Ratjen 2001b

Ratjen F, Comes G, Paul K, Posselt H, Wagner T, Harms K. Effect of continuous antistaphylococcal therapy on the rate of P.aeruginosa acquisition in patients with cystic fibrosis. Pediatric Pulmonology 2001;31(1):13‐6.

Rosenfeld 1999

Rosenfeld M, Emerson J, Accurso F, Armstrong D, Castille R, Grimwood K, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatric Pulmonology 1999;28(5):321‐8.

Rosenfeld 2001

Rosenfeld MR, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, et al. Early pulmonary infection, inflammation and clinical outcomes in infants with cystic fibrosis. Pediatric Pulmonology 2001;32(5):356‐66.

Schulz 1995

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in randomised controlled trials. JAMA 1995;273(5):408‐12.

Smyth 2012

Smyth AR, Walters S. Prophylactic anti‐staphylococcal antibiotics for cystic fibrosis. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.CD001912]

Smyth 2014

Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, et al. European Cystic Fibrosis Society Standards of Care: Best Practice Guidelines. Journal of Cystic Fibrosis 2014;13(Supplement 1):S23‐S42.

Stutman 2002

Stutman HR, Lieberman JM, Nussbaum E, Marks MI. Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomised controlled trial. Journal of Pediatrics 2002;140(3):299‐305.

Thomassen 1984

Thomassen MJ, Klinger JD, Badger SJ, Van Herckren BW, Stern RC. Cultures of thoracotomy specimens confirm usefulness of sputum cultures in cystic fibrosis. Journal of Pediatrics 1984;104(3):352‐6.

UK CF Registry 2012

UK CF Trust. Cystic Fibrosis Trust Patient Registry User’s Guide. Bromley: UK CF Trust, 2012.

UK CF Registry 2013

UK Cystic Fibrosis Trust. UK CF Registry: Annual Data Report 2013. Bromley: Cystic Fibrosis Trust, 2014.

UK CF Trust 2004

UK CF Trust Control of Infection Group. Pseudomonas aeruginosa infection in people with cystic fibrosis: suggestions for prevention and control (2nd edition). UK CF Trust2004.

Winnie 1991

Winnie GB, Cowan RG. Respiratory tract colonisation with Pseudomonas aeruginosa in cystic fibrosis: correlations between anti‐Pseudomonas aeruginosa antibody levels and pulmonary function. Pediatric Pulmonology 1991;10(2):92‐100.

Langton Hewer 2009

Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD004197.pub3]

Wood 2003

Wood DM, Smyth A. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/14651858.CD004197]

Wood 2006

Wood DM, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD004197.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Gibson 2003

Methods

Double‐blind RCT.

Placebo‐controlled.

Parallel design.

Duration: 28 days.

Multicentre based in USA.

Participants

21 participants with a recent positive oropharyngeal culture and isolation of P. aeruginosa from BAL at study entry.

Age: 6 months ‐ 6 years.

Gender: 11 males, 10 females.

Interventions

Treatment: Tobramycin solution for inhalation (300 mg 2x daily for 28 days).

Control: placebo inhalations.

Outcomes

Eradication of P. aeruginosa, nutritional status, modified Shwachman score, adverse effects.

Notes

Oropharyngeal cultures performed at entry and on days 14, 28, 42 and 56 of the study. BAL from the same lobar segment on entry and day 28.

Enrolement was discontinued due to an interim analysis, precipitated by poor accrual of participants, which showed a statistically significant microbiological effect of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Described as a randomised controlled trial stratified by study centre and age (≦ 36 months; > 36 months), but the method of generation of allocation sequence was not stated.

Allocation concealment (selection bias)

Unclear risk

Did not report how allocation was concealed.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Reported as double blind, but paper did not provide any details regarding who was blinded or the method of blinding.

We received the following helpful response from trial authors, regarding placebo:

Active: Preservative free tobramycin sulfate, 60 mg/mL in 5 mL excipient (1/4 normal saline, pH 6.0) in low density polyethylene plastic ampoules inside a foil pouch (PathoGenesis Corporation).

Placebo: 5 mL of vehicle with 1.25 mg of quinine sulfate added as a flavouring agent, packaged identically. PathoGenesis Corporation were responsible for the manufacture of the tobramycin and placebo for inhalation.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Analysed on an intention‐to‐treat basis. Reported data on all participants who were randomised. There were no dropouts reported.

Selective reporting (reporting bias)

Low risk

No evidence of selective reporting found.

Other bias

High risk

Study was stopped early by the Data Monitoring Committee after recruitment of 21 from an anticipated 98 participants because of statistically significant treatment effect in favour of the tobramycin group.

Study received sponsorship support from Chiron, manufacturer of tobramycin for inhalation as used in the study.

Proesmans 2013

Methods

RCT.

Parallel design.

Duration: 3 months.

Single centre based in Europe.

Participants

58 children with CF, all with new isolation of P. aeruginosa (sputum or cough swabs).

Age: median age 9 years, interquartile range (4.7 ‐ 13.1 years).

Gender: 31 male, 27 female.

Lung function: median FEV1 at inclusion 98% predicted.

Interventions

Treatment (n = 29): Inhaled TSI (300 mg 2x daily for 28 days).

Control (n = 29): 3 months combination therapy with inhaled colistin (2 MU 2x daily) + oral ciprofloxacin (10 mg/kg 3x daily).

Outcomes

Primary outcomes
Eradication of P. aeruginosa at the end of treatment.
Secondary outcomes
Time to P. aeruginosa relapse; antibodies (Ab); IgG; FEV1; body mass index; and P. aeruginosa status at 2‐year follow up.

Notes

Participants were then switched to the other arm or treated with IV antibiotics if clinically indicated.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised in blocks of 10. No description given of method of randomisation, nor of any stratification.

Allocation concealment (selection bias)

Unclear risk

Did not report how allocation was concealed.

Blinding (performance bias and detection bias)
All outcomes

High risk

Blinding not possible for participants and clinicians as treatments compared were inhaled versus inhaled and oral. No details regarding whether outcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Intention‐to‐treat analysis on all 58 randomised participants.

Selective reporting (reporting bias)

High risk

Protocol published on ClinicalTrials.gov (identifier: NCT01400750). All pre‐specified outcomes reported.

BMI z score, weight z score and frequency of exacerbations were reported not to have changed significantly for trial participants, but numerical data are not reported.

Other bias

Unclear risk

Primary outcome was assessed at end of treatment which was different for the 2 treatment groups 28 days for TSI participants versus 3 months for colistin/ciprofloxacin participants.

Ratjen 2010

Methods

RCT.

Parallel design.

Duration: 27 months.

Multicentre (21 centres) based in Europe (Germany, France, Spain, Austria, UK, Netherlands).

Participants

123 participants with CF free of P. aeruginosa (88 randomised ‐ 31 participants not randomised because of high P. aeruginosa antibody titres and 4 for other reasons).

Age (mean (SD)): 28‐day TIS 8.7 (7.2) years, 56‐day TIS 8.7 (10.5) years.

Gender: 28‐day TIS 26 (58%) males, 19 (42%) females; 56‐day TIS 22 (51%) males, 21 (49%) females.

Lung function (mean (SD) FEV1 % predicted): 28‐day TIS 80.2 (18.9), 56‐day TIS 87.0 (19.2).

Interventions

Group 1 (n = 45): 28 days of tobramycin solution for inhalation (TSI) (300 mg 2x daily), then stopped treatment.

Group 2 (n = 43): 28 days of tobramycin solution for inhalation (TSI) (300 mg 2x daily), then randomised to a further 28 days (56 days in total).

Outcomes

Primary outcome
Median time to recurrence of any strain of P. aeruginosa.

Secondary outcomes

Proportion of patients free of P. aeruginosa 1 month after the end of treatment

Number and length of hospital admissions for respiratory indications

Occurrence of other pathogens

Changes in FEV1, FVC & FEF25‐75

Weight, height and body mass index.

Notes

Also known as ELITE trial.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Described as randomised, but no description of randomisation techniques given.

Allocation concealment (selection bias)

Unclear risk

Did not report how allocation was concealed.

Blinding (performance bias and detection bias)
All outcomes

High risk

Open‐label study, no attempt at blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

65 patients from 88 randomised achieved primary outcome. A total of 52 participants prematurely withdrawn from trial.

27 participants withdrew from the 28‐day treatment group with the following reasons: loss to follow up (n = 1); protocol deviation (n = 4); recurrence/non‐eradication (n = 21); other (n = 1).

25 participants withdrew from the 56‐day treatment group for the following reasons: withdrawn consent (n = 1); loss to follow up (n = 2); protocol deviation (n = 2); recurrence/no eradication (n = 19); abnormal audiology test (n = 1).

Selective reporting (reporting bias)

High risk

Study reports there were no major short‐ or long‐term (3 and 27 months) changes in spirometry, but does not record the figures for either of the 2 groups. Also, only summary statements and no numerical data are provided for weight, height or BMI.

Other bias

Unclear risk

Recruited fewer participants than planned; actually randomised 88 participants (primary outcome evaluable in 65) ‐ planned randomisation of 100 participants.

Did not randomise 35 participants from the recruited cohort of 123 participants: 31 because of high P. aeruginosa antibody levels, one for an adverse event, one where consent was withdrawn, one for a protocol deviation and one 'other' (unspecified) reason. Participants with raised antibody levels were not included because the investigators believed that they were chronically infected with P. aeruginosa based on their antibody results.

This trial was initially supported by Chiron and later Novartis Pharma, the manufacturer of TSI.

Taccetti 2012

Methods

RCT.

Parallel design.

Duration: 28 days.

Multicentre (13 centres) in Italy.

Participants

223 participants with first ever or new P. aeruginosa infection. New infection defined as P. aeruginosa isolation following bacterial clearance documented by 3 negative cultures within the previous 6 months.

Age: over 1 year.

Gender: 116 male, 107 female.

Interventions

Group A (n = 105; 52 male and 53 female): 28 days 2x daily inhalation of 2 MU colistin with 2x daily doses of ciprofloxacin 15 mg/kg/dose.
Group B (n = 118; 64 male and 54 female): 28 days therapy with TSI (300 mg 2x daily) with 2x daily doses of ciprofloxacin 15 mg/kg/dose.

Outcomes

Primary outcome
P. aeruginosa eradication defined as 3 negative cultures over 6 months.
Secondary outcomes

Lung function (FEV1).

Period of time free of P. aeruginosa.

Isolation of other pathogens including gram‐negative and aspergillus.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation sequence generated by statistical software within permuted blocks of size 10, stratified according to age and FEV1.

Allocation concealment (selection bias)

Low risk

Separation of individuals responsible for randomisation and treatment assignment.

Blinding (performance bias and detection bias)
All outcomes

High risk

Open‐label trial so no blinding of participants nor researchers.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

38 of 223 randomised participants (17%) dropped out of the trial. The biggest reason for dropping out was lack of compliance with follow up protocol (11 from Group A and 13 from Group B) and identification of a pulmonary exacerbation during early eradication therapy (4 from Group A and 5 from Group B). Analysis was by intention‐to‐treat.

Selective reporting (reporting bias)

Unclear risk

We have been unable to locate a published protocol for this trial. The details published on the EudraCT database (number 2008‐006502‐42) describe objectives but not outcomes. In the main paper, the methods section does not describe all the trial objectives. Only eradication, time free of P. aeruginosa and spirometry are described in the methods section. These outcomes plus the additional outcomes of isolation of other organisms and adverse events are described in the results.

Other bias

Low risk

No evidence of other bias identified.
Treggiari 2011

Methods

RCT.

Multi‐centre (57 centres) in the USA.
Trial duration for each participant is 18 months.
Parallel design.

Inhaled tobramycin was provided in an open‐label fashion, while oral ciprofloxacin was provided in a double‐blinded fashion.

Participants

306 participants with CF, previously free of P. aeruginosa or had not had positive isolates for 2 years or more.

Age: 1 year or older and 12 years and younger.

Gender: 150 male, 154 female.

Interventions

All participants received eradication therapy with inhaled tobramycin (Novartis Pharmaceutical Corp) for 28 days with or without ciprofloxacin (Bayer Healthcare AG). The main randomised intervention of nebulised tobramycin, with or without oral ciprofloxacin, commenced after this initial 28 days of treatment:

Group A: cycled therapy;

Group B: culture‐based therapy.

Furthermore, the time from isolation of P. aeruginosa to commencing trial therapy was up to 6 months and in this interval, some participants received antimicrobial therapy.

Outcomes

Primary outcomes
Time to first exacerbation requiring IV therapy.
Proportion of positive cultures in each group.

Secondary outcomes

Clinical
Time to pulmonary exacerbation not requiring IV antibiotic usage or hospitalization.

Frequency of pulmonary exacerbations, hospitalizations, and use of concomitant oral, inhaled, and IV antibiotics.

Anthropometric measures (linear growth, weight gain).

Pulmonary function tests including FVC, FEF25%–75%, and FEV1 (participants 4 years of age and older, able to reproducibly perform spirometry).

Total hospitalization days.

Microbiological

Changes in antibiotic susceptibility patterns (minimal inhibitory concentrations of 12 antibiotics).

Colony morphology.

Presence of mucoid isolates from baseline to the end of the trial.

Emergence of intrinsically aminoglycoside and ciprofloxacin‐resistant non‐pseudomonal organisms (e.g. B. cepacia, A. xylosoxidans, and S. maltophilia).

Adverse events.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization was carried out by permuted blocks, and performed using a computer‐generated sequence.

Allocation concealment (selection bias)

Low risk

Randomization assignment was available at the sites via an interactive voice response system with e‐mail confirmation of the treatment assignment.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Inhaled tobramycin was provided in an open‐label fashion, while oral ciprofloxacin was provided in a double‐blinded fashion.

All trial personnel and participants were blinded to oral therapy assignment but not to cycled or culture‐based treatment allocation. The core trial investigators were blinded to all treatment allocation for the entire study.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only 2 of 306 randomised participants excluded from the analysis (because they did not receive study treatment).

Selective reporting (reporting bias)

Low risk

Data on all primary and secondary outcomes reported.

Other bias

Low risk

No imbalance in baseline characteristics. Central trial team (not local investigators) blinded.

Valerius 1991

Methods

RCT.

Parallel design.

Duration: 27 months.

Single‐centre trial based in Europe.

Participants

26 participants with a recent positive culture who have never received anti‐pseudomonal therapy.

Age: 2 ‐ 9 years.

Gender: 13 males, 13 females.

Interventions

Treatment: oral ciprofloxacin (250 ‐ 750 mg) 2x daily and inhaled colistin (1 MU) for 3 weeks at entry and each time P. aeruginosa isolated.

Control: no anti‐pseudomonas chemotherapy.

Outcomes

Time to chronic colonisation with P. aeruginosa (defined as the presence of P. aeruginosa in monthly routine sputum specimens for 6 consecutive months and/or the development of precipitating serum antibodies against P. aeruginosa).

Notes

Monthly sputum samples.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Described as a RCT without stratification, but the method of generation of allocation sequence was not stated.

Allocation concealment (selection bias)

Unclear risk

Did not report how allocation was concealed.

Blinding (performance bias and detection bias)
All outcomes

High risk

Did not use blinding, interventions different.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Analysed on an intention‐to‐treat basis. Reported data on all participants who were randomised. There were no dropouts reported.

Selective reporting (reporting bias)

Low risk

No evidence of selective reporting found.

Other bias

Low risk

No evidence of other bias identified.
Wiesemann 1998

Methods

RCT.

Double‐blind, placebo‐controlled trial.

Parallel design.

Duration: 2 years.

Multicentre trial based in Europe.

Participants

22 children with P. aeruginosa‐negative throat swabs or sputum cultures for > 1 year and negative serum antibody titers were eligible.

Age: 4 ‐ 18 years.

Gender: 9 males, 13 females.

Interventions

Treatment: nebulised tobramycin 80 mg inhaled 2x daily.

Control: inhaled placebo.

Outcomes

Time to clearance of P. aeruginosa from the airway.

Notes

Monthly sputum or oropharyngeal swabs during trial period.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Allocation sequence was generated using a coin flip for pairs of participants. There is no information as to who was responsible for the coin flip or what controls were in place to ensure validity of the result of the coin flip.

Allocation concealment (selection bias)

Unclear risk

Did not report how allocation was concealed.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Reported as double blind. Participants were blinded by providing a placebo inhalation with a similar taste to the treatment inhalation, but it is not clear whether the clinicians administering the treatment were blinded to treatment allocation.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

2 out of 11 participants withdrew from treatment group; 5 out of 11 participants withdrew from placebo group. The trial was analysed on an available case basis.

Selective reporting (reporting bias)

High risk

Reported there was no change in spirometric pulmonary function during or after the treatment period, but no data were given

Other bias

Low risk

No evidence of other bias identified.

BAL: bronchoalveolar lavage
FEF25‐75: mid‐forced expiratory flow
FEV1: forced expiratory volume at one second
FVC: forced vital capacity
IgG: immunoglobulin G
IV: intravenous
MU: million units
P. aeruginosa: Pseudomonas aeruginosa
RCT: randomised controlled trial
TSI: tobramycin solution for inhalation

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Alothman 2002

Drug tolerability study, not eradication therapy.

Alothman 2005

Drug tolerability study, not eradication therapy.

Ballman 1998

Eradication treatment not used. Observational study.

Brett 1992

Participants allocated to treatment by minimisation on the basis of IgG levels and clinical indications compared to therapy based on clinical indications alone.

Church 1997

Symptomatic treatment not eradication.

Clancy 2013

Participants chronically infected with P. aeruginosa.

Coates 2011

Participants chronically infected with P. aeruginosa.

Frederiksen 1997

Historical control group.

Geller 2007

Pharmacokinetic and drug tolerability study, not eradication therapy.

Gibson 2007

Not randomised and with no allocation concealment.

Goss 2009

Participants chronically infected with P. aeruginosa.

Griese 2002

Case‐control study.

Heinzl 2002

No control group.

Kenny 2009

Retrospective cohort study.

Konstan 2010

Participants chronically infected with P. aeruginosa.

Latzin 2008

The primary aim of this trial was not to evaluate eradication regimens for P. aeruginosa and 112 of 118 participants were treated for an acute exacerbation or suppression of chronic infection with P. aeruginosa.

Lenoir 2007

Trial not designed to look at eradication of P. aeruginosa. At baseline, 47 of 59 participants had chronic infection with P. aeruginosa.

Littlewood 1985

No control group.

Mainz 2014

Sinonasal nebulisation of antibiotic aiming to eradicate from the sinuses only.

Mazurek 2012

Participants chronically infected with P. aeruginosa.

Oermann 2009

Participants chronically infected with P. aeruginosa, not an eradication trial, no randomisation.

Postnikov 2000

No control group and no randomisation.

Postnikov 2007

Not an eradication trial, participants chronically infected with P. aeruginosa.

Prayle 2013

Participants chronically infected with P. aeruginosa.

Ramsey 1999

Participants chronically infected with P. aeruginosa.

Ratjen 2001a

No control group.

Retsch‐Bogart 2008

Participants chronically infected with P. aeruginosa.

Retsch‐Bogart 2009

Participants chronically infected with P. aeruginosa.

Rietschel 2009

Pharmacokinetic study of inhaled tobramycin, not eradication therapy.

Schaad 1997

Symptomatic treatment not eradication.

Schelstraete 2010

No randomisation or eradication therapy.

Schuster 2013

Drug tolerability study in chronic P. aeruginosa infection, not eradication therapy.

Steinkamp 1989

No control group.

Steinkamp 2007

Participants chronically infected with P. aeruginosa.

Taccetti 2005

Primary outcome did not have a control group. Historical controls utilised for other outcomes. No randomisation.

Tramper‐Stranders 2009

Study of prophylaxis against future infection with P. aeruginosa, not of eradication.

Trapnell 2012

Participants chronically infected with P. aeruginosa.

Vazquez 1993

Historical control group.

Wainwright 2011a

Randomised to therapy directed by the results of bronchoalveolar lavage compared to therapy based on clinical indications or upper respiratory samples.

Wainwright 2011b

Participants chronically infected with P. aeruginosa.

P. aeruginosa: Pseudomonas aeruginosa

Characteristics of studies awaiting assessment [ordered by study ID]

Ir a:

Noah 2010

Methods

Single‐centre, randomised, prospective trial.

Participants

Stable children with CF and positive surveillance cultures for P. aeruginosa.

Interventions

Nebulised tobramycin 300 mg 2x daily for 4 weeks or intravenous ceftazidime with tobramycin for 2 weeks at standard weight‐adjusted doses.

Outcomes

Primary efficacy endpoint was change in BAL fluid percentage neutrophils from the most affected lobe at bronchoscopy.

Secondary outcomes included change in BAL fluid differential cell counts, cytokines and bacterial quantity.

Notes

8 participants from a total of 15 had first ever isolate of P. aeruginosa and can be included in this review. Outcome data for these 8 participants not published, author contacted for them.

BAL: bronchoalveolar lavage
CF: cystic fibrosis
P. aeruginosa: Pseudomonas aeruginosa

Characteristics of ongoing studies [ordered by study ID]

Ir a:

TORPEDO Trial

Trial name or title

TORPEDO‐CF (Trial of Optimal Therapy for Pseudomonas Eradication in Cystic Fibrosis)

Methods

Multi‐centre, parallel group, RCT.

Participants

Inclusion criteria
1. Diagnosis of CF
2. Children over the age of 28 days, older children and adult CF participants are all eligible with no upper age limitation
3. Competent adults should provide fully informed written consent to participate in the trial
4. Minors should have proxy consent by the parent or legal guardian and should provide assent where applicable to participate in the trial
5. The participant should have isolated P.aeruginosa and should be either:
a. P. aeruginosa‐naïve (i.e. has never previously isolated P. aeruginosa) or
b. P. aeruginosa‐free (i.e. a minimum of four consecutive cough or sputum samples should be P. aeruginosa‐free within a 12‐month period)
6. The participant should be able to commence treatment no later than 21 days from the date of a P. aeruginosa positive microbiology report

Interventions

Objective: this trial will assess whether 10 days IV ceftazidime with tobramycin is superior to 3 months oral ciprofloxacin. Both treatment regimes will be in conjunction with 3 months nebulised colistin.

Arm A: 14 days IV ceftazidime 50 mg/kg/dose, to a maximum of 3 g 3x daily and IV tobramycin 10 mg/kg/day either 1x daily or in divided doses (maximum 660 mg/day).
Arm B: 3 months oral ciprofloxacin 2x daily (ciprofloxacin dose will be 15 ‐ 20 mg/kg/dose 2x daily for children aged < 5 years and 20 mg/kg/dose 2x daily (maximum 750 mg 2x daily) for those aged ≥ 5 years).
Both treatment arms will receive 3 months of nebulised colistin in conjunction to the randomised treatment. Colistin dose will be as recommended by the UK CF Trust: 1,000,000 units 2x daily for children aged ≤ 2 years and 2,000,000 units 2x daily for children aged > 2 years and adults.

Outcomes

Primary outcome

1. Successful eradication of P. aeruginosa infection 3 months after allocated treatment has started, remaining infection‐free through to 15 months after the start of allocated treatment

Secondary outcomes

1. Time to reoccurrence of original P. aeruginosa infection
2. Re‐infection with a different genotype of P. aeruginosa
3. Lung function (FEV1 , FVC, FEF25‐75)
4. O2 saturation
5. Growth and nutritional status – height, weight and body mass index
6. Number of pulmonary exacerbations
7. Admission to hospital
8. Number of days spent as inpatient in hospital over the 3‐month period after allocated treatment has finished, and between 3 months and 15 months after eradication treatment has finished (other than 14 days spent on initial IV treatment)
9. Quality of life (CFQ)
10. Utility (EQ‐5D)
11. Adverse events
12. Other sputum/cough microbiology (MRSA, B. cepacia complex, Aspergillus, candida infection)
13. Cost per patient (from NHS perspective)
14. Incremental cost effectiveness ratio (cost per successfully treated patient, cost per QALY)
15. Carer burden (absenteeism from school or work)
16. Participant burden (absenteeism from education or work)

Starting date

24/05/2010.

Contact information

Dr Simon Langton Hewer

Bristol Royal Hospital for Children
Paul O'Gorman Building
Upper Maudlin Street

Bristol

BS2 8BJ
UK

Notes

Anticipated end date: 01/11/2014

HTA 07/51/01

A. xylosoxidans: Alcaligenes xylosoxidans
B. cepacia: Burkholderia cepacia
CF: cystic fibrosis
FEF25‐75: mid‐forced expiratory flow
FEV1: forced expiratory volume at 1 second
FVC: forced vital capacity
IV: intravenous
MRSA: Methicillin‐resistant Staphylococcus aureus
NHS: National Health Service
O2: oxygen
od: once daily
P. aeruginosa: Pseudomonas aeruginosa
QALY: quality‐adjusted life year
RCT: randomised controlled trial
S. maltophilia: Stenotrophomonous maltophilia

Data and analyses

Open in table viewer
Comparison 1. Inhaled tobramycin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 1.1
Comparison 1 Inhaled tobramycin versus placebo, Outcome 1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily).

Comparison 1 Inhaled tobramycin versus placebo, Outcome 1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily).

1.1 At 1 month

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 2 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 1.2
Comparison 1 Inhaled tobramycin versus placebo, Outcome 2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily).

Comparison 1 Inhaled tobramycin versus placebo, Outcome 2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily).

2.1 At 1 month

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 At 2 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 At 3 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 At 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.5 At 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Positive respiratory culture for P. aeruginosa (combined available case analysis) Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.3
Comparison 1 Inhaled tobramycin versus placebo, Outcome 3 Positive respiratory culture for P. aeruginosa (combined available case analysis).

Comparison 1 Inhaled tobramycin versus placebo, Outcome 3 Positive respiratory culture for P. aeruginosa (combined available case analysis).

3.1 At 1 month

2

38

Odds Ratio (M‐H, Fixed, 95% CI)

0.06 [0.01, 0.33]

3.2 At 2 months

2

38

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.03, 0.65]

4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.4
Comparison 1 Inhaled tobramycin versus placebo, Outcome 4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case.

Comparison 1 Inhaled tobramycin versus placebo, Outcome 4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case.

4.1 At 1 month

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.06 [0.01, 0.30]

4.2 At 2 months

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.14 [0.03, 0.60]

4.3 At 3 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.14 [0.02, 1.16]

4.4 At 6 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.04 [0.00, 0.48]

4.5 At 12 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.01 [0.00, 0.26]

5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.5
Comparison 1 Inhaled tobramycin versus placebo, Outcome 5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case.

Comparison 1 Inhaled tobramycin versus placebo, Outcome 5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case.

5.1 At 1 month

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.08 [0.02, 0.38]

5.2 At 2 months

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.18 [0.04, 0.73]

5.3 At 3 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.36 [0.05, 2.77]

5.4 At 6 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.83]

5.5 At 12 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.36 [0.05, 2.77]

6 Change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.6
Comparison 1 Inhaled tobramycin versus placebo, Outcome 6 Change in weight from baseline.

Comparison 1 Inhaled tobramycin versus placebo, Outcome 6 Change in weight from baseline.

6.1 At 1 month

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 At 2 months

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 1.7
Comparison 1 Inhaled tobramycin versus placebo, Outcome 7 Adverse events.

Comparison 1 Inhaled tobramycin versus placebo, Outcome 7 Adverse events.

7.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

8 Change in modified Shwachmann score from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.8
Comparison 1 Inhaled tobramycin versus placebo, Outcome 8 Change in modified Shwachmann score from baseline.

Comparison 1 Inhaled tobramycin versus placebo, Outcome 8 Change in modified Shwachmann score from baseline.

8.1 At 1 month

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

8.2 At 2 months

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 2. Oral ciprofloxacin and inhaled colistin versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion colonised with P. aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 2.1
Comparison 2 Oral ciprofloxacin and inhaled colistin versus no treatment, Outcome 1 Proportion colonised with P. aeruginosa.

Comparison 2 Oral ciprofloxacin and inhaled colistin versus no treatment, Outcome 1 Proportion colonised with P. aeruginosa.

1.1 At 3 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 At 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 At 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 3. Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P.aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 3.1
Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 1 Positive respiratory culture for P.aeruginosa.

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 1 Positive respiratory culture for P.aeruginosa.

1.1 In first 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 3.2
Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 2 Adverse events.

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 2 Adverse events.

2.1 Severe cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 4. Nebulised tobramycin 28 days versus 56 days

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected
Analysis 4.1
Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures.

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures.

2 Number of respiratory exacerbations Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 4.2
Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 2 Number of respiratory exacerbations.

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 2 Number of respiratory exacerbations.

2.1 Until recurrence of P. aeruginosa

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse events (up to 3 months) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 4.3
Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 3 Adverse events (up to 3 months).

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 3 Adverse events (up to 3 months).

3.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Productive cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Haemoptysis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.4 Rhinitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.5 Sinusitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.6 Nasopharyngitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.7 Tonsilitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.8 Oropharyngeal pain

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.9 Dysphonia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.10 Headache

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.11 URTI

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.12 Lung disorder

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.13 Bronchitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.14 P. aeruginosa infection

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.15 Influenza

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.16 Otitis media

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.17 Deafness

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.18 Drug level increased

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.19 Pyrexia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.20 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.21 Varicella

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse events (over 3 months) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 4.4
Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 4 Adverse events (over 3 months).

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 4 Adverse events (over 3 months).

4.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Productive cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Haemoptysis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.4 Rhinitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.5 Sinusitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.6 Nasopharyngitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.7 Tonsilitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.8 Oropharyngeal pain

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.9 Dysphonia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.10 Headache

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.11 URTI

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.12 Lung disorder

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.13 Bronchitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.14 P. aeruginosa infection

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.15 Influenza

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.16 Otitis media

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.17 Deafness

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.18 Drug level increased

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.19 Pyrexia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.20 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.21 Varicella

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 5. Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P. aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 5.1
Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 1 Positive respiratory culture for P. aeruginosa.

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 1 Positive respiratory culture for P. aeruginosa.

1.1 In first 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At end of follow up (median 16 months)

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Relative change in % predicted FEV1 from baseline (to mean 54 days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 5.2
Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 2 Relative change in % predicted FEV1 from baseline (to mean 54 days).

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 2 Relative change in % predicted FEV1 from baseline (to mean 54 days).

3 Post‐trial microbiology status Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 5.3
Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 3 Post‐trial microbiology status.

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 3 Post‐trial microbiology status.

3.1 Stenotrophomonas maltophilia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Achromobacter xylosoxidans

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Aspergillus species

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse events leading to trial discontinuation Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 5.4
Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 4 Adverse events leading to trial discontinuation.

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 4 Adverse events leading to trial discontinuation.

4.1 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Photosensitivity

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Wheeze

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.4 Pulmonary exacerbation during early eradication treatment

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.5 Lack of compliance

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 6. Cycled inhaled tobramycin versus culture‐based inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with one or more isolates of P. aeruginosa from respiratory tract Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.1
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

2 Mean 70‐week change in FEV1 % predicted Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.2
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

3 Mean 70‐week change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.3
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

4 Mean 70‐week change in height from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.4
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

5 Time to severe pulmonary exacerbation Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected
Analysis 6.5
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

6 Participants with one or more severe pulmonary exacerbations Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.6
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

7 Time to pulmonary exacerbation (any severity) Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected
Analysis 6.7
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

8 Participants with one or more pulmonary exacerbations (any severity) Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.8
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 8 Participants with one or more pulmonary exacerbations (any severity).

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 8 Participants with one or more pulmonary exacerbations (any severity).

9 Participants with new isolates of Stenotrophomonas maltophilia Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.9
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

10 Participants with one or more serious adverse event Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 6.10
Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Open in table viewer
Comparison 7. Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with one or more isolates of P. aeruginosa from respiratory tract Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.1
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

2 Mean 70‐week change in FEV1 % predicted Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.2
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

3 Mean 70‐week change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.3
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

4 Mean 70‐week change in height from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.4
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

5 Time to severe pulmonary exacerbation Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected
Analysis 7.5
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

6 Participants with one or more severe pulmonary exacerbations Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.6
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

7 Time to pulmonary exacerbation (any severity) Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected
Analysis 7.7
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

8 Participants with one of more pulmonary exacerbation (any severity) Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.8
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 8 Participants with one of more pulmonary exacerbation (any severity).

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 8 Participants with one of more pulmonary exacerbation (any severity).

9 Participants with new isolates of Stenotrophomonas maltophilia Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.9
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

10 Participants with one or more serious adverse event Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Analysis 7.10
Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily).
Figuras y tablas -
Analysis 1.1

Comparison 1 Inhaled tobramycin versus placebo, Outcome 1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily).
Figuras y tablas -
Analysis 1.2

Comparison 1 Inhaled tobramycin versus placebo, Outcome 2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 3 Positive respiratory culture for P. aeruginosa (combined available case analysis).
Figuras y tablas -
Analysis 1.3

Comparison 1 Inhaled tobramycin versus placebo, Outcome 3 Positive respiratory culture for P. aeruginosa (combined available case analysis).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case.
Figuras y tablas -
Analysis 1.4

Comparison 1 Inhaled tobramycin versus placebo, Outcome 4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case.
Figuras y tablas -
Analysis 1.5

Comparison 1 Inhaled tobramycin versus placebo, Outcome 5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 6 Change in weight from baseline.
Figuras y tablas -
Analysis 1.6

Comparison 1 Inhaled tobramycin versus placebo, Outcome 6 Change in weight from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 7 Adverse events.
Figuras y tablas -
Analysis 1.7

Comparison 1 Inhaled tobramycin versus placebo, Outcome 7 Adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Inhaled tobramycin versus placebo, Outcome 8 Change in modified Shwachmann score from baseline.
Figuras y tablas -
Analysis 1.8

Comparison 1 Inhaled tobramycin versus placebo, Outcome 8 Change in modified Shwachmann score from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 2 Oral ciprofloxacin and inhaled colistin versus no treatment, Outcome 1 Proportion colonised with P. aeruginosa.
Figuras y tablas -
Analysis 2.1

Comparison 2 Oral ciprofloxacin and inhaled colistin versus no treatment, Outcome 1 Proportion colonised with P. aeruginosa.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 1 Positive respiratory culture for P.aeruginosa.
Figuras y tablas -
Analysis 3.1

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 1 Positive respiratory culture for P.aeruginosa.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 2 Adverse events.
Figuras y tablas -
Analysis 3.2

Comparison 3 Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin, Outcome 2 Adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures.
Figuras y tablas -
Analysis 4.1

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 2 Number of respiratory exacerbations.
Figuras y tablas -
Analysis 4.2

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 2 Number of respiratory exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 3 Adverse events (up to 3 months).
Figuras y tablas -
Analysis 4.3

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 3 Adverse events (up to 3 months).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 4 Adverse events (over 3 months).
Figuras y tablas -
Analysis 4.4

Comparison 4 Nebulised tobramycin 28 days versus 56 days, Outcome 4 Adverse events (over 3 months).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 1 Positive respiratory culture for P. aeruginosa.
Figuras y tablas -
Analysis 5.1

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 1 Positive respiratory culture for P. aeruginosa.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 2 Relative change in % predicted FEV1 from baseline (to mean 54 days).
Figuras y tablas -
Analysis 5.2

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 2 Relative change in % predicted FEV1 from baseline (to mean 54 days).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 3 Post‐trial microbiology status.
Figuras y tablas -
Analysis 5.3

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 3 Post‐trial microbiology status.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 4 Adverse events leading to trial discontinuation.
Figuras y tablas -
Analysis 5.4

Comparison 5 Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin, Outcome 4 Adverse events leading to trial discontinuation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.
Figuras y tablas -
Analysis 6.1

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.
Figuras y tablas -
Analysis 6.2

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.
Figuras y tablas -
Analysis 6.3

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.
Figuras y tablas -
Analysis 6.4

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.
Figuras y tablas -
Analysis 6.5

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.
Figuras y tablas -
Analysis 6.6

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).
Figuras y tablas -
Analysis 6.7

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 8 Participants with one or more pulmonary exacerbations (any severity).
Figuras y tablas -
Analysis 6.8

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 8 Participants with one or more pulmonary exacerbations (any severity).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.
Figuras y tablas -
Analysis 6.9

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.
Figuras y tablas -
Analysis 6.10

Comparison 6 Cycled inhaled tobramycin versus culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.
Figuras y tablas -
Analysis 7.1

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 1 Participants with one or more isolates of P. aeruginosa from respiratory tract.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.
Figuras y tablas -
Analysis 7.2

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 2 Mean 70‐week change in FEV1 % predicted.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.
Figuras y tablas -
Analysis 7.3

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 3 Mean 70‐week change in weight from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.
Figuras y tablas -
Analysis 7.4

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 4 Mean 70‐week change in height from baseline.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.
Figuras y tablas -
Analysis 7.5

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 5 Time to severe pulmonary exacerbation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.
Figuras y tablas -
Analysis 7.6

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 6 Participants with one or more severe pulmonary exacerbations.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).
Figuras y tablas -
Analysis 7.7

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 7 Time to pulmonary exacerbation (any severity).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 8 Participants with one of more pulmonary exacerbation (any severity).
Figuras y tablas -
Analysis 7.8

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 8 Participants with one of more pulmonary exacerbation (any severity).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.
Figuras y tablas -
Analysis 7.9

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 9 Participants with new isolates of Stenotrophomonas maltophilia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.
Figuras y tablas -
Analysis 7.10

Comparison 7 Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin, Outcome 10 Participants with one or more serious adverse event.

Ir a la figura de la revisiónAbrir en una pestaña nueva
Comparison 1. Inhaled tobramycin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P. aeruginosa (300 mg 2x daily) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 At 1 month

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 2 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Positive respiratory culture for P. aeruginosa (80 mg 2x daily) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 At 1 month

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.2 At 2 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.3 At 3 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.4 At 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.5 At 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Positive respiratory culture for P. aeruginosa (combined available case analysis) Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 At 1 month

2

38

Odds Ratio (M‐H, Fixed, 95% CI)

0.06 [0.01, 0.33]

3.2 At 2 months

2

38

Odds Ratio (M‐H, Fixed, 95% CI)

0.15 [0.03, 0.65]

4 Positive respiratory culture for P. aeruginosa (combined) ‐ best case Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 At 1 month

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.06 [0.01, 0.30]

4.2 At 2 months

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.14 [0.03, 0.60]

4.3 At 3 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.14 [0.02, 1.16]

4.4 At 6 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.04 [0.00, 0.48]

4.5 At 12 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.01 [0.00, 0.26]

5 Positive respiratory culture for P. aeruginosa (combined) ‐ worst case Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 At 1 month

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.08 [0.02, 0.38]

5.2 At 2 months

2

39

Odds Ratio (M‐H, Fixed, 95% CI)

0.18 [0.04, 0.73]

5.3 At 3 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.36 [0.05, 2.77]

5.4 At 6 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 1.83]

5.5 At 12 months

1

18

Odds Ratio (M‐H, Fixed, 95% CI)

0.36 [0.05, 2.77]

6 Change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

6.1 At 1 month

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 At 2 months

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

7.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

8 Change in modified Shwachmann score from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

8.1 At 1 month

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

8.2 At 2 months

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 1. Inhaled tobramycin versus placebo
Ir a la tabla de la revisión
Comparison 2. Oral ciprofloxacin and inhaled colistin versus no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion colonised with P. aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 At 3 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.3 At 12 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.4 At 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 2. Oral ciprofloxacin and inhaled colistin versus no treatment
Ir a la tabla de la revisión
Comparison 3. Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P.aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 In first 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At 24 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Adverse events Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Severe cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 3. Oral ciprofloxacin and inhaled colistin versus inhaled tobramycin
Ir a la tabla de la revisión
Comparison 4. Nebulised tobramycin 28 days versus 56 days

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to next isolation of P. aeruginosa from BAL, sputum or oropharyngeal cultures Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected

2 Number of respiratory exacerbations Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2.1 Until recurrence of P. aeruginosa

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Adverse events (up to 3 months) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Productive cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Haemoptysis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.4 Rhinitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.5 Sinusitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.6 Nasopharyngitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.7 Tonsilitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.8 Oropharyngeal pain

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.9 Dysphonia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.10 Headache

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.11 URTI

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.12 Lung disorder

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.13 Bronchitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.14 P. aeruginosa infection

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.15 Influenza

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.16 Otitis media

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.17 Deafness

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.18 Drug level increased

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.19 Pyrexia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.20 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.21 Varicella

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse events (over 3 months) Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 Cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Productive cough

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Haemoptysis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.4 Rhinitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.5 Sinusitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.6 Nasopharyngitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.7 Tonsilitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.8 Oropharyngeal pain

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.9 Dysphonia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.10 Headache

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.11 URTI

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.12 Lung disorder

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.13 Bronchitis

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.14 P. aeruginosa infection

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.15 Influenza

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.16 Otitis media

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.17 Deafness

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.18 Drug level increased

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.19 Pyrexia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.20 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.21 Varicella

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 4. Nebulised tobramycin 28 days versus 56 days
Ir a la tabla de la revisión
Comparison 5. Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive respiratory culture for P. aeruginosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 In first 6 months

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1.2 At end of follow up (median 16 months)

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Relative change in % predicted FEV1 from baseline (to mean 54 days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3 Post‐trial microbiology status Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3.1 Stenotrophomonas maltophilia

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Achromobacter xylosoxidans

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.3 Aspergillus species

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Adverse events leading to trial discontinuation Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

4.1 Vomiting

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Photosensitivity

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.3 Wheeze

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.4 Pulmonary exacerbation during early eradication treatment

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.5 Lack of compliance

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 5. Inhaled colistin/oral ciprofloxacin versus inhaled tobramycin/oral ciprofloxacin
Ir a la tabla de la revisión
Comparison 6. Cycled inhaled tobramycin versus culture‐based inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with one or more isolates of P. aeruginosa from respiratory tract Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

2 Mean 70‐week change in FEV1 % predicted Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3 Mean 70‐week change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

4 Mean 70‐week change in height from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

5 Time to severe pulmonary exacerbation Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected

6 Participants with one or more severe pulmonary exacerbations Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

7 Time to pulmonary exacerbation (any severity) Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected

8 Participants with one or more pulmonary exacerbations (any severity) Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

9 Participants with new isolates of Stenotrophomonas maltophilia Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

10 Participants with one or more serious adverse event Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 6. Cycled inhaled tobramycin versus culture‐based inhaled tobramycin
Ir a la tabla de la revisión
Comparison 7. Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with one or more isolates of P. aeruginosa from respiratory tract Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

2 Mean 70‐week change in FEV1 % predicted Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

3 Mean 70‐week change in weight from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

4 Mean 70‐week change in height from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

5 Time to severe pulmonary exacerbation Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected

6 Participants with one or more severe pulmonary exacerbations Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

7 Time to pulmonary exacerbation (any severity) Show forest plot

1

Hazard Ratio (Fixed, 95% CI)

Totals not selected

8 Participants with one of more pulmonary exacerbation (any severity) Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

9 Participants with new isolates of Stenotrophomonas maltophilia Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected

10 Participants with one or more serious adverse event Show forest plot

1

Odds Ratio (IV, Fixed, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 7. Ciprofloxacin versus placebo added to cycled and culture‐based inhaled tobramycin
Ir a la tabla de la revisión