Aerosolized antibiotics in cystic fibrosis: an update

Abstract

Inhaled antibiotic therapy, targeting Pseudomonas aeruginosa, is a fundamental component of cystic fibrosis (CF) management. Tobramycin inhalation solution (TIS) was approved in the United States (US) in 1998. Subsequent research efforts focused on developing products with a reduced treatment time burden. Aztreonam for inhalation solution (AZLI), administered via a more efficient nebulizer than TIS, was approved in the US in 2010. Dry powder for inhalation (DPI) formulations provide alternatives to nebulized therapy: tobramycin powder for inhalation (also known as TIP™) was approved in the US in 2013, and colistimethate sodium DPI received European approval in 2012. Other aerosolized antibiotics and regimens combining inhaled antibiotics are in development. Inhaled antibiotic rotation (e.g., TIS alternating with AZLI) is an important concept being actively tested in CF.

Keywords::

• aerosolized antibiotic
• aztreonam lysine
• colistimethate sodium
• cystic fibrosis
• dry powder for inhalation
• inhaled solution
• Pseudomonas aeruginosa
• tobramycin

Financial & competing interests disclosure

SB Fiel has received grants/research support from: CFF, Gilead, Novartis and Vertex; is a Consultant for: Bayer, BI, Novartis and Pfizer; is on Speakers’ Bureau for: Dey, Genentech, Gilead, GSK, Novartis and Pfizer and is on the DMSB of CFF. Technical assistance with editing, figure preparation and styling of the manuscript for submission was provided by M Rolfe, PhD, and L Orloski, PharmD, of Oxford PharmaGenesis Ltd., and was funded by Novartis Pharmaceuticals Corp. The author was fully responsible for all content and editorial decisions and received no financial support or other form of compensation related to the development of this manuscript. The opinions expressed in the manuscript are those of the author, and Novartis Pharmaceuticals Corp. had no influence on the contents. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• Both wet (nebulized solutions) and dry (dry powder for inhalation [DPI]) formulations are available for the delivery of aerosolized antibiotics in patients with cystic fibrosis (CF).

• DPI delivery may reduce the time burden associated with nebulized therapy, and increasingly efficient nebulizers have also been introduced in recent years.

• To date, three inhaled antibiotics have been approved by the US FDA for use in CF: tobramycin inhalation solution (TIS) (TOBI^®, Novartis Pharmaceuticals Corp., East Hanover, NJ, USA), aztreonam lysine for inhalation (AZLI) (Cayston^®, Gilead Sciences, Inc., Foster City, CA, USA) and tobramycin powder for inhalation (TOBI Podhaler™, Novartis Pharmaceuticals Corp., East Hanover, NJ, USA).

• TIS was among the recommended treatments in the 2007 CF Foundation (CFF) guidelines for maintaining lung function and was included (with the same recommendation) in the recently updated 2013 guidelines, in which chronic use of AZLI was also recommended. Both TIS and AZLI received grade A (strong) recommendations from the CFF for use in moderate-to-severe lung disease.

• Tobramycin powder for inhalation, which was developed to improve the efficiency of airway delivery, administration time and patient convenience and satisfaction compared with TIS, received the same FDA-approved indication as TIS in March 2013; it is administered via the Podhaler DPI.

• An additional aerosolized antibiotic, colistimethate sodium DPI, received European approval in February 2012, but is not available in the USA.

• Other aerosolized antibiotics are being investigated in clinical trials; these include new formulations of ciprofloxacin, levofloxacin and amikacin.

• There is continued interest in developing combination regimens, such as combining an inhaled antibiotic with an oral or iv. antibiotic, or with another inhaled antibiotic.

Notes