Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans

Abstract

The in vitro interaction of pentamidine with ketoconazole and with itraconazole was studied with 10 strains of Candida albicans isolated from acquired immunodeficiency syndrome patients and one azole-resistant strain. Although growth curves indicated that concentrations of 1 ,g or more of pentamidine per ml significantly inhibited the growth of C. albicans, MICs and minimum fungicidal concentrations (MFCs) were .10 ,g/ml. Combinations of ketoconazole and pentamidine did not appear to have any significant effect on MICs or MFCs with most strains. However, the azole-resistant strain exhibited a 2-log decrease in MIC when exposed to ketoconazole combined with 1.0 ,ug or more of pentamidine per ml. Similar results were obtained with itraconazole. An Eagle, or paradoxical, effect was observed with four strains exposed to itraconazole alone and in combination with 0.01 and 0.1 ,ug of pentamidine per ml. This effect was not seen when concentrations of pentamidine reached 1.0 ,ug/ml. Although no fungicidal effect was observed with any of these drugs alone, itraconazole combined with 10 ,Ig of pentamidine per ml was fungicidal for eight strains. No signs of antagonism between pentamidine and these two antifungal agents were observed.

Pentamidine Inhibition of Group I Intron Splicing in Candida albicans Correlates with Growth Inhibition

“…The in vivo inhibition of intron splicing supports the hypothesis that ribozyme inhibitors might represent a new class of antimicrobial agents acting on this RNA target (22-24, 27, 29, 30, 35, 46-49). It is not known if variation in the presence of an intron in the 25S rRNA gene of different isolates of C. albicans (2,30) is responsible for the reported variation in the MIC of pentamidine for various isolates of this organism (40). Since inhibition of group I intron splicing ( Fig.…”

“…Although pentamidine has been more widely used to treat P. carinii than C. albicans infections (32), its target in P. carinii remains incompletely defined (9). Pentamidine and a series of analogs have been shown to inhibit the growth of C. albicans in culture (5,40). Topoisomerases have been proposed as a target of pentamidine (9).…”

“…These two strains are closely related based on genetic sequence analysis of variable regions V2 and V3 of the genes encoding 25S rRNA (2). Ten C. albicans clinical isolates, previously tested for their susceptibility to pentamidine (40), were kindly provided by G. St-Germain (Laboratoire de Santé Publique du Québec, Quebec, Canada). C. albicans ATCC 90028, obtained from the American Type Culture Collection (Manassas, Va.), was used as a control for drug susceptibility assays.…”

Antifungal Susceptibility Survey of 2,000 Bloodstream Candida Isolates in the United States

“…Most isolates showed MICs of 0.5 to 2 g/ml, with C. parapsilosis isolates tending to concentrate on the higher end. Paradoxical fungal growth at the highest drug concentrations, the so-called "Eagle" phenomenon, of unknown (but unlikely) in vivo significance (8,40,41) and slight trailing were occasionally observed when testing isolates with this drug. …”

In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp.

“…The antimicrobial agents were selected according to previous reports of synergism when such drugs were combined with antifungal agents against other fungal genera and the oomycete Pythium insidiosum (Afeltra et al, 2002;Chodosh et al, 2000;Jesus et al, 2014;Ku et al, 2010;St-Germain, 1990;Zhai et al, 2010). PNT has been used in prophylaxis of pneumonia caused by Pneumocystis jiroveci in recipients of allogeneic bone marrow transplants and patients with AIDS (Marras et al, 2002).…”