Article

Effect of amphotericin B alone or in combination with rifampicin or clarithromycin against Candida species biofilms

Infectious Diseases Division, Clínica Universidad de Navarra, Pamplona, Spain.
The International journal of artificial organs (Impact Factor: 1.45). 11/2011; 34(9):766-70. DOI: 10.5301/ijao.5000023
Source: PubMed

ABSTRACT Effectiveness of amphotericin B alone or in combination with rifampicin or clarithromycin on the killing of Candida species biofilms was investigated in vitro. Amphotericin B was assayed at 0.005 to 10 mg/ml. Rifampin and clarithromycin were assayed at 10 mg/ml. We studied 7 Candida albicans, 3 Candida parapsilosis, 3 Candida glabrata, 3 Candida krusei and 2 Candida tropicalis strains. Biofilms were developed in 96-well, flat-bottomed microtiter plates for 48 hours. A synergistic effect between amphotericin B and clarithromycin was demonstrated against 66.6% of C. parapsilosis, 66.6% of C. glabrata, and 42.8% of C. albicans biofilms. A synergistic effect between amphotericin B and rifampin was demonstrated against 66.6% of C. parapsilosis, 42.8% of C. albicans, and 33.3% of C. glabrata biofilms. No synergistic effect was observed against C. krusei or C. tropicalis biofilms with any of the combinations. Rifampin or clarithromycin alone did not exert any effect on Candida species biofilms. Rifampin or clarithromycin combinations with amphotericin B might be of interest in the treatment of Candida biofilm-related infections.

0 Bookmarks
 · 
104 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe the in vitro activity of the combination of azithromycin, clarithromycin, minocycline and tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin and micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the M38-A2 technique and the checkerboard microdilution method. The main synergism observed was through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%) and micafungin (70%) as well as clarithromycin with micafungin (73.33%).
    Antimicrobial Agents and Chemotherapy 07/2014; 58(9). DOI:10.1128/AAC.02349-14 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases) that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half (δ/+) does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker α-helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.
    PLoS ONE 03/2013; 8(3):e59094. DOI:10.1371/journal.pone.0059094 · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the activity of fluconazole, caspofungin, anidulafungin and amphotericin B against planktonic and biofilm Candida using a highly sensitive assay measuring growth-related heat production (microcalorimetry). C. albicans, C. glabrata, C. krusei and C. parapsilosis were tested and the MIC was determined by the microbroth dilution method. The antifungal activity was determined by isothermal microcalorimetry at 37°C in RPMI-1640. For planktonic Candida, heat flow was measured in presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous glass beads for 24 h, exposed to serial dilution of antifungals for 24 h and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat-flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for biofilm Candida. Fluconazole (MIC, 0.25->512 μg/ml) and amphotericin B (MIC, 0.25-1 μg/ml) showed higher MIC values than anidulafungin (MIC, 0.03-0.5 μg/ml) and caspofungin (MIC, ≤0.125-0.5 μg/ml). Against biofilm Candida, fluconazole activity was reduced by >1000-fold compared to planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activity. Fluconazole induced growth of planktonic C. krusei at sub-MIC concentrations. At high concentrations of caspofungin (>8 μg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was observed. Microcalorimetry enabled real-time evaluation of antifungal activity against planktonic and biofilm Candida. It can be used in future for evaluation of new antifungals, study of resistant strains and antifungal combinations.
    Antimicrobial Agents and Chemotherapy 02/2014; 58(5). DOI:10.1128/AAC.00057-14 · 4.57 Impact Factor