Amphotericin B (AMB) Tolerance with Aspergillus Species.



Mortality remains high in invasive aspergillosis despite high-dose and aggressive therapy with AMB. Most in vitro susceptibility studies have employed only relatively few isolates of aspergilli and the concept of tolerance to this polyene has been little investigated. This study assessed in vitro activity of AMB against 70 clinical isolates of aspergilli: A. fumigatus = Af, 30 strains: A. flavus = Afl, 20 strains; A. niger = An. 20 strains, with special emphasis on ascertainment of minimum lethal concentrations (MLC) and the tolerance phenomenon. Susceptibility tests were accomplished using a macro broth dilution procedure. SAAMF medium, 25*C incubation temperature, an inoculum of 1X10 4 conidia/ml (via hemacytometer count), and two-fold dilutions of Fungizone powder solution to provide final test concentrations ranging from 0.14 to 18.47 ug/ml. All tests were run in duplicate with growth controls and a Paecilomyces sp. for drug reproducibility quality control. Minimum inhibitory concentrations (MIC) were read at the time of positivity of the growth control and 24 hours later. 0.1 ml aliquots were removed from all tubes exhibiting no turbidity and plated on drug-free media. The MLC was considered the lowest concentration at which 2.31 ug/ml were considered resistant. Aspergilli which showed MICs 2.31 were judged tolerant. All isolates were consistently susceptible to AMB (MIC50, 2nd reading, 0.29, 0.58, and 0.29 ug/ml, respectively. for Af, Afl, and An). MLCs were >1.16 ug/ml in 30% of Af,100% of Afl, and 75% of An; hence, according to study criteria. 10% of Af, 85% of Afl, and 55% of An were tolerant. Fungicidal effect in 45/70 (64%) aspergillial isolates studied were higher than can usually be achieved in patient plasma or tissue.

abstract No: 


Full conference title: 

ICAAC 33rd, 1993
    • ICAAC 33rd