Novel inhaled combined antibiotic formulations in the treatment of Pseudomonas aeruginosa airways infections in cystic fibrosis

Abstract

In cystic fibrosis, chronic airways infection caused by Pseudomonas aeruginosa can be treated with inhaled antibiotics such as inhaled tobramycin, aztreonam or colistin. However, biofilm formation induced by this bacterium can reduce the effectiveness of such therapies and can contribute to antibiotic resistance. Inhaled antibiotic combination might represent an optimal antibiofilm strategy in this setting. This review discusses the rationale for combining the antibiotics as well as some emerging or existing combinations. Most of the combinations except for fosfomycin/tobramycin are at an early stage of development. The latter combination was found to be effective in Phase II clinical studies and is planned to be tested in Phase III trials. The clinical data on long-term efficacy are currently missing, but the existing evidence as well as the unmet therapeutic need can prompt the further evaluation of such compounds.

Keywords:

• cystic fibrosis
• fosfomycin/tobramycin
• inhaled antibiotics
• Pseudomonas aeruginosa
• tobramycin

Financial & competing interests disclosure

The author has no 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In cystic fibrosis (CF), chronic airways infection is the main hallmark of the disease and can be a negative prognostic factor.

• The main bacteria involved is Pseudomonas aeruginosa but other such as Burkholderia cepacia complex or Staphylococcus aureus are frequently isolated.

• Inhaled antibiotics such as tobramycin, colistin or aztreonam are effective in eradicating or in reducing the bacterial density in such infections.

• Often this infection is difficult to eradicate due to antibiotic resistance and due to biofilm formation and in an attempt to overcome it antibiotic rotation is used.

• Other approaches might be represented by antibiotic combinations or by antibiotic-potentiating combinations.

• Among the most promising antibiotic combinations, fosfomycin/tobramycin is the most advanced in terms of clinical development.

• Fosfomycin/tobramycin was demonstrated to eradicate the biofilm forming P. aeruginosa in clinical studies, but long-term efficacy is not yet known.

• Other promising combinations are represented by clarithromycin/tobramycin or colistin/tobramycin combinations, but they are still at a very early stage of development.