In Vitro Interaction of Amphotericin B and Cotrimoxazole against Clinical Isolates of Aspergillus Species Using RPMI and AM3

J. AFELTRA1, E. DANNAOUI 1, J. F. G. MEIS 2, P. E. VERWEIJ 1

Author address: 

1Department of Medical Microbiology, University Medical Center, Nijmegen, Netherlands, 2Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.

Abstract: 

Background: To evaluate the activity of Amphotericin B (AMB) in combination with cotrimoxazole (SXT) against 60 clinical Aspergillus isolates: A. fumigatus (20), A. flavus (10), A. niger (10), A. terreus (10) and A. ustus (10). Methods: The susceptibility testing was performed according to NCCLS guidelines (M38P) using RPMI 1640 and AM3 media. A two dimensional, two agent broth microdilution checkerboard technique was used to study the interaction between the agents. Final concentrations ranged for 16 to 0.03 mg/l for AMB and from 8/160 to 0.12/2.5 mg/l for SXT (1:20 ratios). The microtitration plates were incubated at 35oC and read after 48h. The MICs were determinated as the lowest concentration of the drugs (alone or in combination) that showed ³95% inhibition of growth compared with the drug-free control (MIC-0). Drug interaction effects were defined on the basis of fractional inhibitory concentration index (FIC) as follows: synergistic, ≤0.5; additive, >0.5 but ≤ 1; indifferent, >1 but ≤2; antagonistic >2. Results: For AMB the geometric mean, range, MIC50 and MIC90 were 0.71 mg/l, 0.12-8 mg/l, 1.1 mg/l in RPMI and 3.7 mg/l, 1-32 mg/l, 4 mg/l and 16 mg/l, respectively, in AM3. SXT showed poor activity in both media. The combination AMB-SXT showed antagonistic interaction in 45 of 60 isolates (75% FIC range: 2.1-4.5) in RPMI and was synergistic against only 1 isolate (range of FIC: 0.28). In AM3, the combination was antagonistic against 29 of 60 isolates (48% FIC range: 2.2-4.5) and synergistic against 13 of 60 isolates (21.6%, FIC range: 0.25-0.5). Antagonism was found among isolates from all species tested. Conclusions: AMB-SXT is antagonistic against most of the strains tested. The concomitant use of SXT and AMB in invasive aspergillosis should be evaluated further.
2002

abstract No: 

M-849

Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd