[Administration of anti-infective agents through the inhaled route]

To report the doses of inhaled anti-infective agents described in the literature for both the adult and paediatric population. In the case of anti-infective agents which were not approved for inhaled administration, to propose the optimum manner in which these should be prepared in order to achieve osmolality and pH values as similar as possible to physiological values.

A search was carried out of Pubmed (between 1960 and 2005) for each of the anti-infective agents using the words "inhalation OR inhaled OR aerosol OR aerosolized OR nebulized". We also consulted text books, Micromedex and the technical specifications of the pharmaceutical products. Nebulised solutions were prepared using the drugs for which information was found. The drugs approved for inhaled administration were prepared according to the manufacturers recommendations. For anti-infective agents which were not approved for inhaled administration, the raw materials and the branded drug products for intravenous administration available at our hospital were diluted using physiological saline solution and/or water for injection up to a final volume of 4-5 ml. The osmolality and pH values of all the solutions were measured. The optimum form of preparation was considered to be one with values as close as possible to between 150 and 550 mOsm/kg for osmolatity osmolality and 7 +/- 0.5 for pH.

Information about doses of 18 inhaled anti-infective agents was found (12 antibiotics, 5 antifungals and 1 antiviral); paediatric doses were described in 9 of these. Three of the anti-infective agents reviewed were approved for inhaled use in adult patients and four in paediatric patients. Of the 48 recommendations for dilution suggested for administration, two had an osmolality > 1,100 mOsm/kg and 5 an osmolality of < 100 mOsm/kg. Two dilutions had a pH > 8 and 14 a pH < 5.

There is limited literature regarding the doses of anti-infective agents for inhaled administration. The majority of anti-infective agents are not approved for inhaled administration. The dilution of the raw material or proprietary drugs with water or physiological saline solution for intravenous administration achieved solutions with appropriate osmolality in the majority of cases. Some of the solutions have extreme osmolality and/or pH levels, implying that it is reasonable to expect a greater risk of bronchospasm.