Abstract
Aztreonam is a monobactam antibacterial with bactericidal activity against a wide range of aerobic Gram-negative bacteria, including Pseudomonas aeruginosa. Aztreonam lysine for inhalation solution (AZLI) does not contain the potentially inflammatory component arginine, which is used as a buffer in the intravenous formulation.
Two phase III, randomized, placebo-controlled trials (AIR-CF1 and AIR-CF2) have been completed with AZLI in cystic fibrosis patients with pulmonary P. aeruginosa infection. In AIR-CF1, respiratory symptoms were significantly improved with AZLI compared with placebo, as assessed by the respiratory symptoms domain of the Cystic Fibrosis Questionnaire-Revised, a disease-specific, patient-reported outcome instrument. The mean treatment effect exceeded the minimal clinically important difference.
In AIR-CF2, AZLI was compared with placebo following a 28-day course of tobramycin inhalation solution. AZLI was associated with a significant delay in the need for inhaled or intravenous antipseudomonal antibacterials, as determined by the presence of one of four predefined symptoms shown to be predictive of pulmonary exacerbations.
An open-label extension of these trials (AIR-CF3) also demonstrated clinical efficacy with repeated courses of AZLI over 18 months and was not associated with sustained reductions in P. aeruginosa susceptibility.
AZLI was also associated with improved pulmonary function and reductions in P. aeruginosa density in sputum in clinical trials.
The tolerability profile of AZLI was generally similar to that of placebo in randomized controlled trials, with respiratory symptoms being the most frequently reported adverse events.
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References
Davis PB, Drumm M, Konstan MW. State of the art: cystic fibrosis. Am J Respir Crit Care Med 1996; 154(5): 1229–56
Cystic Fibrosis Foundation. Patient registry: annual data report 2008. Bethesda (MD): Cystic Fibrosis Foundation, 2009
Flume PA, O’Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007 Nov 15; 176(10): 957–69
Cystic Fibrosis Foundation. About cystic fibrosis [online]. Available from URL: http://www.cff.org/AboutCF/ [Accessed 2010 Jul 16]
Cystic Fibrosis Foundation. About cystic fibrosis — frequently asked questions [online]. Available from URL: http://www.cff.org/AboutCF/Faqs/ [Accessed 2010 Jul 16]
UK CF Registry Annual Data Report 2008 [online]. Available from URL: http://www.cftrust.org.uk/aboutcf/publications/cfregistryreports/UK_CF_Registry-Annual_Data_Report_2008.pdf [Accessed 2010 Aug 9]
Hodson ME, Penketh AR, Batten JC. Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Lancet 1981 Nov 21; 2(8256): 1137–9
Wall MA, Terry AB, Eisenberg J, et al. Inhaled antibiotics in cystic fibrosis [letter]. Lancet 1983 Jun 11; 1(8337): 1325
Littlewood JM, Miller MG, Ghoneim AT, et al. Nebulised colomycin for early pseudomonas colonisation in cystic fibrosis [letter]. Lancet 1985 Apr 13; 1(8433): 865
Jensen T, Pedersen SS, Garne S, et al. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J Antimicrob Chemother 1987 Jun; 19(6): 831–8
Hodson ME. Antibiotic treatment: aerosol therapy. Chest 1988 Aug; 94 (2 Suppl): 156S–62S
Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999 Jan 7; 340(1): 23–30
Ramsey BW, Dorkin HL, Eisenberg JD, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med 1993 Jun 17; 328(24): 1740–6
Moss RB. Administration of aerosolized antibiotics in cystic fibrosis patients. Chest 2001 Sep; 120 (3 Suppl): 107S–13S
Hodson ME, Gallagher CG, Govan JR. A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis. Eur Respir J 2002 Sep; 20(3): 658–64
Sermet-Gaudelus I, Le Cocguic Y, Ferroni A, et al. Nebulized antibiotics in cystic fibrosis. Pediatric Drugs 2002; 4(7): 455–67
Tiddens H. Inhaled antibiotics. Pediatr Pulmonol 2004; 26 Suppl.: 92–4
Geller DE. Aerosol antibiotics in cystic fibrosis. Respir Care 2009 May; 54(5): 658–70
Garcia-Contreras L, Hickey AJ. Aerosol treatment of cystic fibrosis. Crit Rev Ther Drug Carrier Syst 2003; 20(5): 317–56
Novartis. TOBI® (Tobramycin inhalation solution, USP) [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/tobi.pdf [Accessed 2010 Aug 12]
Novartis Pharmaceuticals UK Ltd. Tobi® (tobramycin 300mg/5mL nebuliser solution): summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/emc/medicine/19020/spc/ [Accessed 2010 Aug 12]
Cheer SM, Waugh J, Noble S. Inhaled tobramycin (TOBI®): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs 2003; 63(22): 2501–20
Fernandez JD, Santiago RT, Matacon MP, et al. Inhaled aztreonam therapy in patients with cystic fibrosis colonized with “Pseudomonas aeruginosa” [in Spanish]. An Esp Pediatr 1994; 40(3): 185–8
Bristol-Myers Squibb. Azactam® (aztreonam for injection, USP) [online]. Available from URL: http://packageinserts.bms.com/pi/pi_azactam.pdf [Accessed 2010 Jul 22]
Gibson RL, Retsch-Bogart GZ, Oermann C, et al. Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatr Pulmonol 2006 Jul; 41(7): 656–65
Brewer NS, Hellinger WC. The monobactams. Mayo Clin Proc 1991; 66: 1152–7
Mulligan MS, Hevel JM, Marletta MA, et al. Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc Natl Acad Sci U S A 1991 Jul 15; 88(14): 6338–42
Grasemann H, Kurtz F, Ratjen F. Inhaled L-arginine improves exhaled nitric oxide and pulmonary function in patients with cystic fibrosis. Am J Respir Crit Care Med 2006; 174: 208–12
Dietzsch HJ, Gottschalk B, Heyne K, et al. Cystic fibrosis: comparison of two mucolytic drugs for inhalation treatment (acetylcysteine and arginine hydrochloride). Pediatrics 1975 Jan; 55(1): 96–100
Cayston® (aztreonam for inhalation solution): US prescribing information. Foster City (CA): Gilead Sciences, Inc., 2010 Feb
European Medicines Agency. Aztreonam lysine (Cayston®) powder and solvent for nebuliser solution: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu [Accessed 2010 Jul 16]
McCoy K, Retsch-Bogart G, Gibson RL, et al. Microbiologic resistance and clinical efficacy of aztreonam lysine for inhalation (AZLI) in cystic fibrosis (CF) [poster no. 142]. 31st European Cystic Fibrosis Conference; 2008 Jun 11–14; Prague
McCoy K, Retsch-Bogart G, Gibson RL, et al. Relevance of established susceptibility breakpoints to clinical efficacy of inhaled antibiotic therapies in cystic fibrosis [poster no. 418]. 22nd Annual North American Cystic Fibrosis Conference; 2008 Oct 23–25; Orlando (FL)
Oermann CM, McCoy K, Retsch-Bogart G, et al. Antibiotic susceptibility of P. aeruginosa isolates following repeated exposure to aztreonam for inhalation solution in patients with cystic fibrosis [poster no. 278]. 23rd Annual North American Cystic Fibrosis Conference; 2009 Oct 15–17; Minneapolis (MN)
Perry JD, Laine L, Hughes S, et al. Recovery of antimicrobial-resistant Pseudomonas aeruginosa from sputa of cystic fibrosis patients by culture on selective media. J Antimicrob Chemother 2008 Mar 3; 61: 1057–61
Burns JL, Griffith A. Pseudomonas aeruginosa killing curves for aztreonam in the presence of cystic fibrosis sputum or porcine gastric mucin [poster no. 332]. 17th Annual North American Cystic Fibrosis Conference; 2003 Oct 16–19; Anaheim (CA)
Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135: 1223–32
McCoy KS, Quittner AL, Oermann CM, et al. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med 2008; 178: 921–8
Retsch-Bogart GZ, Burns JL, Otto KL, et al. A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Pulmonol 2008 Jan; 43(1): 47–58
Oermann CM, Retsch-Bogart GZ, Quittner AL, et al. An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. Epub 2010 Jul 29
Wainwright C, Nakamura C, Geller DE, et al. A double-blind, multinational, randomized, placebo-controlled trial evaluating aztreonam for inhalation (AZLI) in patients with cystic fibrosis (CF), mild lung disease and P. aeruginosa (PA) [abstract no. 81 plus poster]. 33rd European Cystic Fibrosis Society Conference; 2010 Jun 16–19; Valencia
Assael BM, La Rosa M, Knoop C, et al. Aztreonam for inhalation solution (AZLI) head to head trial, a comparative trial vs. tobramycin nebuliser solution (TNS) in cystic fibrosis (CF) patients with Pseudomonas aeruginosa (PA): results of first treatment cycle [abstract plus oral presentation]. 33rd European Cystic Fibrosis Society Conference; 2010 Jun 16–19; Valencia
PARI’s eFlow included in Gilead’s NDA submission for aztreonam lysine for inhalation [media release]. 2007 Nov 26 [online]. Available from URL: http://www.medicalnewstoday.com/articles/89823.php
PARI Pharma’s Altera delivers Gilead’s Cayston in head-to-head study with torbramycin inhalation solution [media release]. 2010 Jun 21 [online]. Available from URL: http://www.drugs.com/clinical_trials/pari-pharma-s-altera-delivers-gilead-s-cayston-head-head-study-tobramycin-inhalation-solution-9674.html
American Thoracic Society. Cystic Fibrosis Questionnaire (CFQ); Cystic Fibrosis Questionnaire Revised (CFQ-R) [online]. Available from URL: http://qol.thoracic.org/sections/instruments/ae/pages/cfq-cfq-r.html [Accessed 2010 Jul 22]
Quittner AL, McCoy KS, Montgomery AB. Inhaled antibiotics to treat stable patients with cystic fibrosis and pseudomonas aeruginosa (PA): measuring patient perception of symptom improvement [poster no. 280]. 21st Annual North American Cystic Fibrosis Conference; 2007 Oct 3–6; Anaheim (CA)
Quittner AL, Modi AC, Wainwright C, et al. Determination of the minimal clinically important difference scores for the cystic fibrosis questionnarie-revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest 2009; 135: 1610–8
Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001 Sep; 139(3): 359–65
Acknowledgements and Disclosures
The manuscript was reviewed by: M.E. Hodson, Department of Cystic Fibrosis, The Royal Brompton Hospital, London, England; C.M. Oermann, Department of Pediatrics, TCH Clinical Care Center, Baylor College of Medicine, Houston, Texas, USA; H.A.W.M. Tiddens, Department of Pediatric Pulmonology and Allergology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands.
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was also offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
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Plosker, G.L. Aztreonam Lysine for Inhalation Solution. Drugs 70, 1843–1855 (2010). https://doi.org/10.2165/10484070-000000000-00000
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DOI: https://doi.org/10.2165/10484070-000000000-00000