Background: Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation. Material and Methods: Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library. Results: Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides. Conclusions: Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.

Anidulafungin, caspofungin, and micafungin killing activities against Candida glabrata, Candida bracarensis, and Candida nivariensis were evaluated by the time-kill methodology. The concentrations assayed were 0.06, 0.125, and 0.5 g/ml, which are achieved in serum. Anidulafungin and micafungin required between 13 and 26 h to reach the fungicidal endpoint (99.9% killing) against C. glabrata and C. bracarensis. All echinocandins were less active against C. nivariensis. Candida glabrata follows Candida albicans as the second or third most prevalent cause of candidemia worldwide (1). C. glabrata presents decreased antifungal susceptibility to fluconazole and other current antifungal drugs and can rapidly acquire resistance (2). Candida bracarensis and Candida nivariensis, two species closely related to C. glabrata, have been recently described (3, 4), but there is scarce information on the prevalence, antifungal susceptibility patterns, and clinical significance of these cryptic species (1, 5-7). The present study aimed to determine the killing activities of echinocandins against C. glabrata, C. bracarensis, and C. nivariensis (Table 1). Strains were identified by metabolic properties (ATB ID 32C; bioMérieux, Marcy l'Étoile, France) and molecular methods, as previously described (5, 7).Caspofungin (Merck Sharp & Dohme, Madrid, Spain), micafungin (Astellas Pharma, Madrid, Spain), and anidulafungin (Pfizer SLU, Madrid, Spain) were dissolved in dimethyl sulfoxide. Further dilutions were prepared in standard RPMI 1640 medium (Sigma-Aldrich, Madrid, Spain). MICs (defined as minimum concentrations that produce Ն50 growth reduction) were determined following the M27-A3 document (8). Time-kill studies were carried out on microtiter plates for the computer-controlled microbiological incubator BioScreen C MBR (LabSystems, Vantaa, Finland) in RPMI 1640 (final volume, 200 l; inoculum, 1 ϫ 10 5 to 5 ϫ 10 5 CFU/ml). The echinocandin concentrations assayed were 0.06, 0.125, and 0.5 g/ml, which are achieved in serum after standard doses (9). Plates were incubated at 36 Ϯ 1°C without agitation. At 0, 2, 4, 6, 8, 24, and 48 h, aliquots of 6 or 10 l were removed from both the control and each test solution well, serially diluted in phosphate-buffered saline (PBS), and plated onto Sabouraud agar to determine the number of CFU per milliliter. Each experiment was performed twice for each isolate (10-13). The antifungal carryover effect was determined as formerly reported (12).Time-kill data were fitted to the exponential equation N t ϭ N 0 ϫ e kt , where t is incubation time, N t represents viable yeast cells at time t, N 0 is the starting inoculum, and k is the killing or growing rate. The goodness of fit for each isolate/drug was assessed by the r 2 value (Ͼ0.8). The times needed to achieve 50, 90, 99 and 99.9% reductions in growth (t 50 , t 90 , t 99 , and t 99.9 , respectively) were calculated from the k value, as described previously (12). Analysis of variance was performed to determine significant dif-

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Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.

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