Background: In patients with refractory fungal infection there are anecdotal reports of successful outcome with the use of amphotericin B in combination with rifampin. Methods: We tested the effects of combination of amphotericin B (AMB) and other antibiotics, azithromycin (AZN), clarithromycin (CLN), erythromycin (ERN), gentamicin (GEN) and rifampin (RFN) against 32 isolates of yeast and filamentous fungi. The isolates were as follows; Candida krusei (5), Candida parapsilosis (5), Torulopsis glabrata (10), Aspergillus spp (6), Penicillum spp (2), Fusarium spp (3) and Mucor (1). The MIC for each drug alone was determined according to the NCCLS guidelines. Drug combinations were tested by using checkerboard and time kill assays. Results: In combination with AZN, synergism was observed in 19 isolates of Candida (mean FIX= 0.44) and 3 isolates of filamentous fungi (mean FIX= 0.50). With CLN, synergism was observed in 19 isolates of Candida (mean FIX= 0.47) and one isolate of fungi. Synergism was also observed in 17 isolates of Candida (mean FIX= 0.50) and one isolate of filamentous fungi in combination of AMB and ERN. Combination of Gen and AMB showed synergism in only 4 isolate of Candida (mean FIX= 0.47) and 4 isolates of filamentous fungi (mean FIX= 0.5). Rifampin showed synergism in combination with AMB against 18 isolates of Candida (mean FIX= 0.45) and 8 isolates of filamentous fungi (mean FIX= 0.45) Conclusions: Our data showed that combination of AMB with antibacterial antibiotic was beneficial against most of the tested Candida spp and some of the filamentous fungi. The combinations of the cell membrane active AMB with antibacterial agents that cause inhibition of protein or nucleic acid synthesis have synergistic in vitro activity against yeast and filamentous fungi. We are planning to study these combinations in vivo.
Full conference title:
43rd Interscience Conference on Antimicrobial Agents
- ICAAC 43rd