In vitro antifungal activity of phenothiazines and their combination with amphotericin B against different Candida species La ´ szlo ´ Galgo ´ czy, Andrea Ba ´ csi, Mo ´ nika Homa, Ma ´ te ´ Vira ´ gh, Tama ´ s Papp and Csaba Va ´ gvo ¨ lgyi Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Summary Candidiosis is a mycosis that is currently increasingly affecting the population in consequence of its frequency and the severity of its complications, especially among immunocompromised hosts. In this work, the in vitro anticandidal activities of two phenothiazines (PTZs), chlorpromazine (CPZ) and trifluoperazine (TFP), and their combinations with amphotericin B (AMB) were tested against 12 different Candida strains representing 12 species (Candida albicans, Candida glabrata, Candida guillermondii, Candida inconspicua, Candida krusei, Candida lusitaniae, Candida lypolitica, Candida norvegica, Candida parapsilosis, Candida pulcherrima, Candida tropicalis and Candida zeylanoides). When used alone, both tested PTZs exerted antifungal effects against these strains. In their combinations, these PTZs and AMB mainly acted antagonistically at higher concentrations, but additively and synergistically at lower concentrations as concerns the clinically most important species (C. albicans and C. parapsilosis). For C. albicans, only synergistic interactions were revealed between CPZ and AMB. Synergistic, additive or no interactions were demonstrated between the investigated compounds for the most PTZ-susceptible (C. glabrata to TFP and C. krusei to CPZ) and insusceptible strains (C. glabrata to CPZ and C. lypolitica to TFP). Key words: Candida spp., chlorpromazine, trifluoperazine, amphotericin B, drug interaction. Introduction In immunocompromised hosts, Candida species are among the most common causative agents of debili- tating mucosal and life-threatening invasive fungal infections. 1,2 The Candida species most frequently isolated from clinical sources is Candida albicans, 3 but infections caused by Candida parapsilosis among neo- nates have recently dramatically increased in num- ber. 4,5 Agents for the treatment of candidiosis are available in clinical practice, but are limited to some polyenes (amphotericin B, AMB), pyrimidine analogues (fluorocytosine), azole families of drugs and 1,3-beta- glucan synthase inhibitors (echinocandins). AMB is appreciably toxic and has serious side-effects (e.g. kidney damage), while resistance to azoles, fluorocyto- sine and echinocandins among Candida species is very common. 6–9 There is therefore considerable interest in the development of potent anticandidal drugs which can act synergistically with AMB, thereby allowing the use of a decreased therapeutic concentration. Such compounds would be advantageous as the basis of less toxic therapy. 10 Chlorpromazine (CPZ) and trifluoperazine (TFP) are used as antipsychotic drugs of the phenothiazine (PTZ) group. 10 Their antibacterial and antifungal effects have been demonstrated, 10–16 and data on their in vitro activities against some yeasts are also available. 17–20 For the Candida species C. albicans, Candida glabrata, Candida krusei, C. parapsilosis and Candida tropicalis, the minimal inhibitory concentrations (MICs) of CPZ and TFP were found by an agar dilution method to be 15– 40 lg ml )1 , 17 and by a broth dilution method to be 17.5– 35 lg ml )1 . 18 Synergistic interactions between CPZ and AMB have been observed against C. albicans. 16 However, Correspondence: La ´ szlo ´ Galgo ´ czy, Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Ko ¨ ze ´ p fasor 52, H-6726, Szeged, Hungary. Tel.: +36 62 544 005. Fax: +36 62 544 823. E-mail: galgoczi@gmail.com Accepted for publication 23 November 2010 Original article Ó 2011 Blackwell Verlag GmbH doi:10.1111/j.1439-0507.2010.02010.x mycoses Diagnosis,Therapy and Prophylaxis of Fungal Diseases