Objectives: The primary objective of the study was to obtain susceptibility data for fusafungine on recent clinical bacterial and fungal isolates responsible for infections of the upper respiratory tract or belonging to the oral commensal flora.
The secondary objective was to evaluate the capacity of fusafungine to select resistant mutants and to verify the absence of cross resistance to usual antibiotics in these mutants.
Background: Fusafungine, a combination of several enniatins, has been shown to display activity against many microorganisms responsible for infections of the respiratory tract, along with anti-inflammatory activity. However, data on recent clinical isolates involved in respiratory tract infections (RTI) need to be obtained to reassess the antibacterial and antifungal activity of fusafungine.
Methodology: MICs of fusafungine were determined for 202 recent clinical isolates involved in upper RTI (Streptococcus, Staphylococcus, Haemophilus, Neisseria, Moraxella, anaerobes), 189 clinical isolates of bacterial species and fungi belonging to commensal flora and 89 Gram-positive strains from collection (Staphylococcusspp, Enterococcus spp, Streptococcus spp) harbouring characterised mechanisms of resistance to the antimicrobials used in the treatment of RTI. Bactericidal activity of fusafungine was tested against methicillin-resistant Staphylococcus aureus ATCC 43300 and Streptococcus pyogenes CIP 56-52 at the concentration of 2 times and 10 times the MIC. Selection of fusafungine resistant mutants was carried out with those two strains ofS. aureus and S. pyogenes by serial passages and by one-step selection on solid media.
Results: MIC50s and MICs90 of fusafungine for all the Gram-positive micro-organisms tested, aerobic, or anaerobic, were equal to 16 and 64 mg/L, respectively. Fusafungine was inactive against the Gram-negative microorganisms tested (MIC >1024 mg/L), except for Fusobacterium and Prevotella (MICs = 32-64 mg/L),Branhamella catarrhalis (MIC = 8-32 mg/L) and Neisseria meningitidis (MIC = 16 mg/L). All strains of Candidaalbicans were inhibited by 32 mg/L of fusafungine whereas Candida glabrata was less susceptible (MICs 16 - >256 mg/L). The presence of resistance genes in the Gram-positive micro-organisms studied did not affect susceptibility to fusafungine. Fusafungine was not bactericidal at 18 h for S. aureus ATCC 43300 and S. pyogenes CIP 56-52. No mutant with increased MIC of fusafungine could be selected after 51 passages in liquid medium in the presence of the antibiotic or in solid medium.
Conclusion: Fusafungine was uniformly active against the tested Gram-positive organisms and fungi involved in RTI with MICs generally equal to or less than 32 mg/L. Its activity was similar to that reported several years ago with no acquisition of resistance in the studied strains. Moreover, no staphylococcal or streptococcal mutant with increased MIC of fusafungine could be selected in vitro and there was no cross-resistance between the antibiotics commonly used for the treatment of RTI and fusafungine.
Full conference title:
- RICAI 24th (2004)