In vitro activity of colistin as single agent and in combination with antifungals against filamentous fungi occurring in patients with cystic fibrosis

Abstract

Summary Because published reports indicate that the antibiotic colistin (COL) has antifungal properties, this study investigated the antifungal in vitro activity of COL as single agent and in combination with the antifungal compounds voriconazole (VRC), caspofungin (CAS) and amphotericin B (AMB) against Scedosporium/Pseudallescheria spp., Exophiala dermatitidis and Geosmithia argillacea. In total, susceptibility was determined for 77 Scedosporium/Pseudallescheria spp., 82 E. dermatitidis and 17 G. argillacea isolates. The minimal inhibitory concentrations (MICs) of COL and the antifungals as single compound and in combination were determined with MIC test strips. Drug interactions were detected by crossing the MIC test strips at a 90º angle. The fractional inhibitory concentration index was used to categorise the drugs’ interaction. The MIC50 value of COL was 12 μg ml−1 for S. prolificans, 16 μg ml−1 for P. apiosperma, 16 μg ml−1 for P. boydii, 12 μg ml−1 for E. dermatiditis and 6 μg ml−1 for G. argillacea. VRC was the most active drug in combination without any antagonism with the exception of few P. boydii isolates. COL as single agent and in most combinations with antifungals exhibits in vitro antifungal activity against filamentous ascomycetes occurring in cystic fibrosis patients and may offer a novel therapeutic option, especially for multidrug‐resistant S. prolificans.

Emerging pathogen in immunocompromised hosts: Exophiala dermatitidis mycosis in graft‐versus‐host disease

“…However, growth is inhibited in the presence of creatinine or nitrites as the sole source of nitrogen . Given that such confirmatory testing does not routinely take place, and that the fungus can have a yeast‐like appearance with conventional staining, misidentification as Candida species or Cryptococcus species has been reported . It is therefore important to maintain a clinical suspicion for this mycosis, to make an accurate diagnosis promptly.…”

“…In one of the few in vitro studies, the combination of terbinafine with amphotericin resulted in improved MIC for the polyene drug . Finally, in vitro activity of colistin against Exophiala species has been demonstrated, and the use of this agent has been suggested in cystic fibrosis patients with pulmonary infection .…”

Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

“…It is also interesting to note that nonantifungal drugs, such as colistin and some psychotropes (e.g., chlorpromazine and trifluoperazine), exert some in vitro activity against Scedosporium spp. (101)(102)(103). Voriconazole could potentiate the effect of colistin, although the combination did not meet criteria for synergism in most cases (102).…”

“…(101)(102)(103). Voriconazole could potentiate the effect of colistin, although the combination did not meet criteria for synergism in most cases (102). A potentiating effect of a mucolytic agent (N-acetyl-L-cysteine) with conventional antifungals has also been suggested (104).…”

Invasive Mold Infections in Solid Organ Transplant Recipients

“…A recent in vitro study suggests synergistic activity of the antibacterial agent colistin with voriconazole against Scedosporium spp. [ 98 ]. Success of combinations therapy of azole and terbinafine has been reported in small case series [ 99 , 100 ].…”