Biochemical characteristics of inhaled antibiotics related to tolerability.

Introduction: Inhaled antibiotics are used in the treatment of various respiratory diseases, including cystic fibrosis (CF), non-CF bronchiectasis, and ventilator-associated pneumonia. While some of these drugs are marketed as ready-to-use formulations, others require prior manipulation, such as dilution or reconstitution procedures that are often not standardized. Furthermore, certain antibiotics are only approved for intravenous administration, making it necessary to develop specific protocols for their preparation and use via the inhaled route. Their biochemical properties may also compromise patient safety and tolerability. The aim of this study was to assess how frequently preparation methods and biochemical parameters of inhaled antibiotic solutions are described in the scientific literature. Additionally, we explored their prevalence of use in our country and evaluated their biochemical characteristics to assess tolerability.

Methods: A literature review was conducted using the MEDLINE database to identify studies describing the dilutions used for the administration of inhaled antibiotics. In addition, a nationwide survey was carried out to assess the dilutions currently used in hospital clinical practice. Biochemical analyses were performed in parallel to determine the pH, osmolality, and sodium and chloride ion concentrations of the solutions employed. Excipients present in each formulation were recorded based on information from the product's summary of characteristics.

Results: The literature review identified 533 full-text publications describing 737 different inhaled antibiotic mixtures. Of these, 476 were not standardized. Only 190 mixtures included precise dilution instructions, while just 31 provided data on pH and 28 on osmolality. The national survey revealed a high prevalence of inhaled antibiotic use among participating hospitals, with 22 centres (64.7%) reporting the use of intravenous formulations administered via inhalation. Laboratory analyses showed that some of the evaluated dilutions fell outside the acceptable tolerability range, particularly those involving reconstitution of dry powders or dilution of concentrated intravenous solutions.

Conclusion: There is limited information in the scientific literature regarding preparation methods and the biochemical characteristics of inhaled antibiotic solutions. Off-label use of intravenous formulations for inhalation is widespread, and some of the dilutions used exhibit biochemical parameters outside the recommended tolerability range, which may compromise both the safety and effectiveness of treatment.