Fusafungine

Summary

Local antimicrobial therapy often has a beneficial effect in both acute and chronic infections of the respiratory tract. Indeed, contrary to systemic antimicrobial administration, inhalation or aerosolisation delivers the drug directly to the site of infection. Even at low dosages, this results in local effective drug concentrations, without adverse reactions.

The spectrum of antimicrobial activity of fusafungine, a cyclohexa-depsipeptidic antimicrobial of fungal origin for local use, has been defined by determination of the minimum concentration of the drug that inhibits the growth of 90% of the strains belonging to a species. The breakpoint concentration of fusafungine for clinical outcome is 40 mg/L. Fusafungine displays bacteriostatic activity on the Gram-positive cocci responsible for infections of the respiratory tract: Streptococcus (including S. pneumoniae) and Staphylococcus, including the methicillin-resistant (Methi-R) strains, which represent more than 30% of the strains isolated in hospitalised patients. Indeed, 60% of the 190 studied strains were Methi-R with the KTG-MLS phenotype and therefore resistant to all the antibacterials commonly used in infections of the respiratory tract, while only 7% of the strains were resistant to fusafungine. Moreover, in vitro, fusafungine did not induce either direct bacterial resistance or cross-resistance with systemic antibacterials. This suggests that there is no risk of selection of multiresistant microorganisms with repeated fusafungine treatments and that fusafungine does not interfere with the efficacy of concomitant systemic antimicrobial therapy.

Fusafungine also has antibacterial activity against Mycoplasma pneumoniae and Legionella pneumophila and antifungal activity against Candida albicans, 3 pathogens that are responsible for infections of the lower respiratory tract.

Subminimal inhibitory concentrations of fusafungine inhibit the adherence of Haemophilus influenzae to epithelial cells in culture, suggesting that this anti-adherence effect is involved in the therapeutic efficacy reported for the drug in Haemophilus infections of the respiratory tract, despite the high minimum inhibitory concentrations against this pathogen. Thus, fusafungine should prevent the colonisation of the nasopharyngeal mucosa by Haemophilus in healthy subjects and, more widely, should prevent infections due to adherent bacteria.

In conclusion, fusafungine is an antimicrobial drug developed for local administration with proven, marked therapeutic efficacy in infections of the respiratory tract.