FUSAFUNGINE - AN ANTIMICROBIAL AGENT FOR THE LOCAL TREATMENT OF RESPIRATORY-TRACT INFECTIONS

Local antimicrobial therapy often has a beneficial effect in both acut e and chronic infections of the respiratory tract. Indeed, contrary to systemic antimicrobial administration, inhalation or aerosolisation d elivers the drug directly to the site of infection. Even at low dosage s, this results in local effective drug concentrations, without advers e reactions. The spectrum of antimicrobial activity of fusafungine, a cyclohexadepsipeptidic antimicrobial of fungal origin for local use, h as been defined by determination of the minimum concentration of the d rug that inhibits the growth of 90% of the strains belonging to a spec ies. The breakpoint concentration of fusafungine for clinical outcome is 40 mg/L. Fusafungine displays bacteriostatic activity on the Gram-p ositive cocci responsible for infections of the respiratory tract: Str eptococcus (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 there fore resistant to all the antibacterials commonly used in infections o f the respiratory tract, while only 7% of the strains were resistant t o fusafungine. Moreover, in vitro, fusafungine did not induce either d irect bacterial resistance or cross-resistance with systemic antibacte rials. This suggests that there is no risk of selection of multiresist ant microorganisms with repeated fusafungine treatments and that fusaf ungine does not interfere with the efficacy of concomitant systemic an timicrobial therapy. Fusafungine also has antibacterial activity again st Mycoplasma pneumoniae and Legionella pneumophila and antifungal act ivity against Candida albicans, 3 pathogens that are responsible for i nfections of the lower respiratory tract. Subminimal inhibitory concen trations of fusafungine inhibit the adherence of Haemophilus influenza e to epithelial cells in culture, suggesting that this anti-adherence effect is involved in the therapeutic efficacy reported for the drug i n Haemophilus infections of the respiratory tract, despite the high mi nimum inhibitory concentrations against this pathogen. Thus, fusafungi ne should prevent the colonisation of the nasopharyngeal mucosa by Hae mophilus in healthy subjects and, more widely, should prevent infectio ns due to adherent bacteria.In conclusion, fusafungine is an antimicro bial drug developed for local administration with proven, marked thera peutic efficacy in infections of the respiratory tract.