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PubMed1995

Synergy of fluconazole with human monocytes or monocyte-derived macrophages for killing of Candida species.

Possible synergy between fluconazole and monocyte-derived macrophages (MDM) for significant killing of Candida species and between fluconazole and monocytes for increased candidacidal activity were studied. Human serum in test medium (RPMI 1640 with 10% fresh autologous human serum) was highly fungistatic for Candida species. Fluconazole in test medium, even at high concentrations, was not fungicidal. Monocytes alone were fungicidal for all Candida species and synergized with fluconazole for increased killing of a fluconazole-sensitive and a fluconazole-resistant Candida albicans isolate. MDM obtained by culturing for 3 or 5 days were not significantly fungicidal for C. albicans but could synergize with fungistatic fluconazole for significant killing. MDM alone killed Candida krusei and Candida glabrata but did not synergize with fluconazole for significantly increased killing. These results, which demonstrate synergy of fluconazole and mononuclear phagocytes for killing, help explain the in vivo efficacy of fluconazole against candidiasis.

Antifungal Agents↗
PubMed1995

Itraconazole susceptibilities of fluconazole susceptible and resistant isolates of five Candida species.

The in-vitro susceptibilities of 1380 isolates of five Candida species were determined in order to establish whether isolates resistant to fluconazole were cross-resistant to itraconazole. IC50 values were determined by a broth microdilution method. 690 Candida albicans isolates, seven Candida glabrata isolates, seven Candida krusei isolates, 120 Candida parapsilosis isolates and 37 Candida tropicalis isolates were susceptible to both fluconazole (IC50 < or = 32 mg/L) and itraconazole (IC50 < or = 4 mg/L). Twenty eight of 160 C. albicans isolates (17.5%), 180 of 293 C. glabrata isolates (61.4%), six of 48 C. krusei isolates (12.5%), and 10 of 18 C. tropicalis isolates (55.5%) resistant to fluconazole (IC50 > or = 64 mg/L) were also resistant to itraconazole (IC50 > or = 8 mg/L). In contrast, drug-specific resistance to itraconazole was not observed in any of the isolates tested. However, the itraconazole IC50s for fluconazole susceptible isolates were lower than those for fluconazole resistant isolates, which suggests that patients who fail fluconazole treatment might require itraconazole at higher dosages than usual.

Antifungal Agents↗
PubMed1997

Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer.

An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.

Adolescent↗
PubMed1998

Voriconazole against fluconazole-susceptible and resistant candida isolates: in-vitro efficacy compared with that of itraconazole and ketoconazole.

We compared the in-vitro activity of fluconazole, itraconazole, ketoconazole and voriconazole against 67 blood isolates of Candida spp. exhibiting a wide range of fluconazole MICs (0.125 to >64 mg/L). Voriconazole was the most potent in vitro, followed by itraconazole, ketoconazole and fluconazole. Itraconazole and voriconazole had in-vitro activity against fluconazole-susceptible and -resistant candida isolates. Higher itraconazole and voriconazole MICs were observed in isolates exhibiting higher fluconazole MICs, suggesting cross-resistance. Itraconazole and voriconazole MICs of > or =16 mg/L were observed only in Candida albicans and Candida tropicalis. Candida krusei and Candida glabrata exhibited itraconazole MICs of 0.5-1 mg/L and voriconazole MICs of 0.25-0.5 mg/L.

Antifungal Agents↗
PubMed1999

In-vitro activity of dicationic aromatic compounds and fluconazole against Cryptococcus neoformans and Candida spp.

We investigated the in-vitro activity of three selected dicationic aromatic compounds for nine clinical isolates of Cryptococcus neoformans and 93 clinical isolates of Candida spp., representing 12 different species, using a broth macrodilution method following NCCLS recommendations. All the clinical isolates were also tested for fluconazole susceptibility. The in-vitro data demonstrate that compounds 39 and 57 have excellent in-vitro activity for all tested strains (MIC 0.19-1.56 mg/L) except Candida pelliculosa. Moreover, compound 39 showed excellent in-vitro fungicidal activity against Candida krusei, Candida glabrata, Candida lusitaniae and Cryptococcus neoformans with MFCs in the range 0.39-6.25 mg/L. Both compounds 39 and 57 showed excellent in-vitro activity against fluconazole-resistant Candida albicans isolates, including a C. albicans strain that contains all known fluconazole-resistant mechanisms. Comparing MIC data from compounds 21, 39 and 57 with fluconazole, we found a statistically significant difference only with compound 39 (P = 0.043). However, comparing MFC data from compounds 21, 39 and 57 with fluconazole, we found statistically significant differences with all three compounds (P < 0.00001). These data indicate the potential antifungal breadth of two bis-benzimidazoles (compounds 39 and 57) as antifungal agents against yeasts. If it can be determined that compounds 39 and 57 are effective and non-toxic in vivo, the prospect of these compounds as clinically useful antifungal agents will be enhanced.

Antifungal Agents↗
PubMed2004

In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002-2003.

OBJECTIVES: The antifungal drug susceptibilities of 351 isolates of Candida species, obtained through active laboratory-based surveillance in the period January 2002-December 2003, were determined (Candida albicans 51%, Candida parapsilosis 23%, Candida tropicalis 10%, Candida glabrata 9%, Candida krusei 4%). METHODS: The MICs of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin were established by means of the broth microdilution reference procedure of the European Committee on Antibiotic Susceptibility Testing. RESULTS AND CONCLUSIONS: Amphotericin B and flucytosine were active in vitro against all strains. A total of 24 isolates (6.8%) showed decreased susceptibility to fluconazole (MIC > or = 16 mg/L) and 43 (12.3%) showed decreased susceptibility to itraconazole (MIC > or = 0.25 mg/L). Voriconazole and caspofungin were active in vitro against the majority of isolates, even those that were resistant to fluconazole.

Antifungal Agents↗
PubMed2005

Antimicrobial peptides enhance the candidacidal activity of antifungal drugs by promoting the efflux of ATP from Candida cells.

OBJECTIVES: To establish a novel strategy of fungal infection control. METHODS: We examined the influences of antimicrobial peptides including a synthesized short lactoferrin peptide (FKCRRWQWRM, Peptide 2; Pep2) on the synthesis of Candida cell wall polysaccharides, ergosterol synthesis, membrane permeability and the efflux of ATP. RESULTS: Colony formation of Candida albicans was synergistically suppressed by a combination of low concentrations of each drug and peptide. All peptides and amphotericin B, but not itraconazole, revealed weak inhibitory activities against ergosterol synthesis and the peptides weakly suppressed the synthesis of Candida cell wall components, glucan, mannan and chitin. Cell membrane permeability was not only increased by these peptides but also clearly increased by both amphotericin B and itraconazole. ATP efflux was however up-regulated by low concentrations of the peptides, especially by Pep2 and Hst5, although both antifungal drugs did not exert any influence on ATP efflux. The expression of the Candida drug resistance genes 1 and 2 (CDR1 and CDR2) was increased by both drugs, but this increase was suppressed by each peptide. In addition, larger amounts of amphotericin B and itraconazole remained in Candida cells in the presence of Pep2 or Hst5 due to the lower excretion. The effects of both peptides on ATP efflux and increase of intercellular amphotericin B and itraconazole were blocked by anion channel inhibitors 4,4'-diisothiocyanatestilbene-2, 2'-disulphonic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid. CONCLUSIONS: The examined peptides, especially Pep2 and Hst5, enhance the candidacidal activity of antifungal drugs by promoting anion channel-associated ATP efflux from Candida cells and decreasing efflux of the drugs, which could be useful clinical applications.

ATP-Binding Cassette Transporters↗
PubMed2002

Combined detection of mannanaemia and antimannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species.

A novel strategy for the diagnosis of systemic candidosis was evaluated, based on the combination of two enzyme immunoassays that detect a candida oligomannoside repetitive epitope expressed in large amounts by Candida albicans (Platelia Candida Ag), and antibodies against C. albicans mannan, the major cell-wall immunogen in which this epitope is present (Platelia Candida Ab). Sera were selected retrospectively from intensive care and haematology patients with clinically suspected systemic candidosis, and from whom Candida spp. had been isolated from normally sterile sites. Of the 21 patients infected with C. albicans, 13 had positive antigenaemia and 14 had a positive antibody response, including eight patients who were antigenaemia negative. The sensitivity of the combined tests was 100%. In patients infected with C. glabrata (n = 12) or C. tropicalis (n = 10), the sensitivity was 83% and 80%, respectively. For the remaining patients, infected with C. parapsilosis (n = 10), C. krusei (n = 8) or C. kefyr (n = 2), the sensitivity of the combined tests was 40%, 50% and 50%, respectively. At least one of the serological tests was positive before yeast growth occurred in 60% of patients for whom a serum sample was available before blood culture sampling. An increase in serological test positivity to >80% was observed for sera obtained around the date of positive culture, irrespective of the Candida species isolated. These results suggest that regular serological monitoring for both mannanaemia and anti-mannan antibodies in at-risk patients may contribute to the early diagnosis of candidosis.

Adult↗
PubMed1979

A biochemical explanation for lipid accumulation in Candida 107 and other oleaginous micro-organisms.

The biochemical explanation for lipid accumulation was investigated principally in Candida 107 and, for comparison, in the non-oleaginous yeast Candida utilis. There were no significant differences between these two yeasts in their control of glucose uptake; in both yeasts, the rates of glucose uptake were independent of the growth rate and were higher in carbon-limited chemostat cultures than in nitrogen-limited cultures. There was no lipid turnover in either yeast, as judged from [14C]acetate uptake and subsequent loss of 14C from the lipid of steady-state chemostat cultures. Acetyl-CoA carboxylase from both yeasts was similar in most characteristics except that from Candida 107 was activated by citrate (40% activation at 1 mM). The enzyme from Candida 107 was relatively unstable and, when isolated from nitrogen-limited (lipid-accumulating) cultures, was accompanied by a low molecular weight inhibitor. The reason for lipid accumulation is attributed to the decrease in the intracellular concentration of AMP as cultures become depleted of nitrogen. As the NAD+-dependent isocitrate dehydrogenase of Candida 107, but not C. utilis, requires AMP for activity, the metabolism of citrate through the tricarboxylic acid cycle in the mitochondria becomes arrested. In Candida 107, but not in C. utilis, there is an active ATP:citrate lyase which converts the accumulating citrate, when it passes into the cytosol, into acetyl-CoA and oxaloacetate. The former product is then available for fatty acid biosynthesis which is stimulated by the high ATP concentration within the cells, by the activation of acetyl-CoA carboxylase by citrate and by the provision of NADPH generated as oxaloacetate is converted via malate to pyruvate. Similar characteristics were evident in oleaginous strains of Rhodotorula glutinis and Mucor circinelloides but not in non-oleaginous representatives of these species.

ATP Citrate (pro-S)-Lyase↗
PubMed1997

Cloning and characterization of a gene (LIP1) which encodes a lipase from the pathogenic yeast Candida albicans.

Extracellular phospholipases are demonstrated virulence factors for a number of pathogenic microbes. The opportunistic pathogen Candida albicans is known to secrete phospholipases and these have been correlated with strain virulence. In an attempt to clone C. albicans genes encoding secreted phospholipases, Saccharomyces cerevisiae was transformed with a C. albicans genomic library and screened for lipolytic activity on egg-yolk agar plates, a traditional screen for phospholipase activity. Two identical clones were obtained which exhibited lipolytic activity. Nucleotide sequence analysis identified an ORF encoding a protein of 351 amino acid residues. Although no extensive homologies were identified, the sequence contained the Gly-X-Ser-X-Gly motif found in prokaryotic and eukaryotic lipases, suggesting a similar activity for the encoded protein. Indeed, culture supernatants from complemented yeast cells contained abundant hydrolytic activity against a triglyceride substrate and had no phospholipase activity. The data suggest that C. albicans, in addition to phospholipases, also has lipases. Southern blot analyses revealed that C. albicans may contain a lipase gene (LIP) family, and that a lipase gene(s) may be present in Candida parapsilosis, Candida tropicalis and Candida krusei, but not in Candida pseudotropicalis, Candida glabrata or S. cerevisiae. Northern blot analyses showed that expression of the LIP1 transcript, the cloned gene which encodes a lipase, was detected only when C. albicans was grown in media containing Tween 80, other Tweens or triglycerides as the sole carbon source, and not in Sabouraud Dextrose Broth or yeast/peptone/dextrose media. Additionally, carbohydrate supplementation inhibited LIP1 expression. Cloning this gene will allow the construction of LIP1-deficient null mutants which will be critical in determining the role of this gene in candidal virulence.

Amino Acid Sequence↗
PubMed1986

Proliferation of human peripheral blood mononuclear cells induced by Candida albicans and its cell wall fractions.

Glutaraldehyde-inactivated cells and cell-wall fractions of Candida albicans were studied for their capacity to induce or inhibit the in-vitro proliferation of human peripheral blood mononuclear cells (PBMC), as measured by 3H-thymidine incorporation. Both the intact cells (CA) and a phosphorylated gluco-mannan-protein complex of the cell wall (GMP), in microgram doses, were strong inducers of PBMC proliferation, with a peak of activity at 6-9 days of culture and varying with the PBMC donor. A significant but much lower proliferation was observed on exposure of PBMC to a low-protein (less than 3% by weight) mannan component (M) of the cell wall. Both a hot-alkali extracted mannan-protein complex (M-alk), comparable to GMP in crude chemical composition, and an alkali-insoluble cell-wall glucan (GG) were inactive. None of the Candida fractions induced a lymphoproliferation of umbilical cord blood cells and all fractions, except GG, were equally effective in binding human anti-Candida antibodies as shown by a sensitive ELISA-inhibition assay. Moreover, a monoclonal antibody against the class II determinant of the HLA complex inhibited PBMC proliferation irrespective of the Candida antigen used. Taken together, the data shows that in inducing lymphoproliferation, Candida fractions act as specific antigens rather than as non-specific mitogens. Use of intact Candida cells and chemically-defined cell-wall components appears preferable to use of undefined antigenic mixtures as stimulators of PBMC proliferation.

Adult↗
PubMed1990

The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics.

This study investigated whether oral candida infection in diabetics and adhesion of Candida albicans to buccal epithelial cells in vitro were related. Buccal cells from 50 patients with diabetes mellitus showed a significant increase in adhesion of C. albicans strain CDS 88 compared with those collected from 50 non-diabetic controls matched for age, sex and denture status. Oral candida carriage, candida infection and secretor status were also investigated in both groups. The frequency of carriage was increased, but not significantly, and there was a significantly higher incidence of candida infection in diabetic patients compared with controls. Diabetic patients who were non-secretors had a significantly increased frequency of oral candida carriage.

Candida albicans↗
PubMed1988

Detection of specificity of a new antigen in Candida tropicalis and its evaluation by taxonomic DNA analyses.

Monospecific factor serum for identifying Candida tropicalis was obtained either from rabbit antiserum to heated cells of C. tropicalis M 1519 (S 96) or from antiserum to C. tropicalis IFO 1400, by adsorption with heated cells of Candida albicans serotype A, or C. albicans (A) and Candida krusei, respectively. We designated this adsorbed serum factor t serum. The monospecific factor serum reacted with 31 out of 32 strains of C. tropicalis, only when tested on heat-treated cell antigens, whereas it did not react with any of 72 strains of the six other medically important species of Candida. The morphological and physiological characteristics of the one strain of C. tropicalis that did not react with the factor t serum, designated the t- -strain, were shown to be similar to those of the type strain of C. tropicalis by most of the methods employed for identifying Candida. Therefore, cell wall mannan from the t- -strain was compared with that from several typical strains of C. tropicalis for its specificity by the precipitation reaction and also for its 1H-nuclear magnetic resonance spectrum. The results showed that these mannans are similar to each other serologically and physicochemically, suggesting that the new antigen t is not mannan. Taxonomic characterization of the t-- and several typical strains of C. tropicalis was carried out by determining the mol% G+C of their DNA and also their DNA homology. Although the mol% G+C values of four typical strains of C. tropicalis were fairly similar (35.2 to 36.2 mol% by the Tm method and 35.5 to 36.4 mol% by the HPLC method), the t- -strain had a G+C content of 44.1 (Tm) and 43.3 (HPLC) mol%. Furthermore, the DNAs of the t- -strain and the type strain of C. tropicalis showed only 18.2% relatedness. These results suggest that the antigen corresponding to serum factor t exists only in the cell wall of C. tropicalis strains, not in those of the other medically important Candida, and that the t- -strain should not be classified as C. tropicalis. In conclusion, the taxonomic value and usefulness of factor t serum is primarily for differentiating C. tropicalis from C. albicans serotype A serologically.

Antigens, Fungal↗
PubMed1999

Effective inhibition of Candida albicans growth by the combination of murine peritoneal neutrophils and activated macrophages.

The effect of leukocytes on the anti-Candida activity of neutrophils was examined. Murine neutrophils which were purified from casein-induced peritoneal cells inhibited the mycelial growth of Candida albicans. This anti-Candida activity of neutrophils was augmented by the addition of spleen cells prepared from mice pretreated with bacterial lipopolysaccharide 3 hr before, but not from non-treated mice. The population in the spleen cells, which enhanced the anti-Candida activity of neutrophils, was plastic-plate adherent, nylon-fiber columns adherent and anti-Mac-1 antigen-positive. These immunological profiles suggested that the enhancing cells are classified to splenic macrophages. Peritoneal-exudated macrophages from mice treated with lipopolysaccharide also augmented the anti-Candida activity of neutrophils. These results suggest that the anti-Candida activity of neutrophils may be upregulated by activated macrophages.

Animals↗
PubMed2003

Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans.

Oral administration of lactoferrin (LF), an innate-defense protein present in exocrine secretions such as milk and in neutrophils, is reported to improve host-protection against infections with microorganisms including pathogenic fungi, possibly due to an immunomodulatory effect. This study aimed to evaluate the effect of bovine LF feeding on peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Time course analysis during the 14 days following Candida-priming revealed that LF administration slightly increased the number of peritoneal exudate cells, and significantly enhanced the production of superoxide anion (O2(-)) and nitric oxide (NO) by peritoneal macrophages at day 7. LF administration facilitated NO production and Candida hyphal-growth inhibition by macrophages derived from Candida-primed mice but not non-primed mice, suggesting that the action of LF is dependent on the immune status of the host. LF administration altered the kinetics of cytokines in the peritoneal lavage fluid of Candida-primed mice. Enhancement of cytokine levels by LF was observed for IL-12 at day 5 and IFN-gamma at day 9, but not for TNF-alpha or IL-10. In conclusion, LF feeding augmented the activities of macrophages in a manner dependent on Candida-priming and these effects may be related to enhanced cytokine levels.

Animals↗
PubMed2001

A novel bovine lactoferrin peptide, FKCRRWQWRM, suppresses Candida cell growth and activates neutrophils.

To identify potent new antifungal agents, the Candida cell growth inhibitory activities of six lactoferrin (Lf) peptides consisting of 6-25 amino acid residues (peptide 1, FKCRRWQWRMKKLGAPSITCVRRAF lactoferricin B; peptide 2, FKCRRWQWRM; peptide 2', FKARRWQWRM; peptide 3, GAPSITCVRRAF; peptide 4, RRWQWR; and peptide 5, RWQWRM) were examined. Of these, peptide 2 strongly suppressed the multiplication of Candida cells, but other peptides showed only weak activities. In two strains of C. albicans, the minimum inhibitory concentration 100 of peptide 2 (17.3+/-2.2 microM and 17.5+/-2.4 microM) was close to that of miconazole (13.0+/-1.7 microM and 13.1+/-1.6 microM) but markedly different from that of amphotericin B (0.52+/-0.09 microM and 0.56+/-0.11 microM). The suppression of Candida cell growth was additively increased by a combination of peptide 2 with amphotericin B and miconazole. Peptides 1, 3, 4 and 5 and Lf suppressed iron uptake by Candida cells, inversely correlated with their Candida cell growth inhibition activities. However, iron uptake was not inhibited by peptide 2. In addition, peptide 2 upregulated Candida cell killing activity of polymorphonuclear leukocytes (PMN) increasing their superoxide generation, protein kinase C activity, p38 MAPK activity and the expression of p47phox. These results indicated that the main antimicrobial activity of the Lf peptides is dependent on the N-terminal half of Lf and that the PMN upregulatory activity of peptide 2 and additive function of peptide 2 with antifungal drugs are useful for prophylaxis and control of candidiasis.

Amino Acid Sequence↗
PubMed1997

Coaggregation of Candida albicans with oral Fusobacterium species.

Nine strains of oral Fusobacterium were examined for their ability to coaggregate in vitro with four strains of the oral yeast. Candida albicans. All of the Fusobacterium nucleatum strains and Fusobacterium periodontium and Fusobacterium sulci coaggregated to various degrees with all of the Candida strains. Fusobacterium alocis, Fusobacterium mortiferum and Fusobactrium simiae strains did not coaggregate with any of the Candida strains. Exposure of the coaggregating Fusobacterium strains but not the Candida strains to heat, trypsin, and proteinase K eliminated coaggregation. Amphotericin B or trichodermin treatment of the yeast species had no effect. The reactions were inhibited by addition of 0.1 M mannose, glucosamine and alpha-methyl mannoside. All coaggregating pairs were disaggregated by the addition of sodium dodecyl sulfate, but nonionic detergents had no effect. The addition of 2.0 M urea completely reversed coaggregation. Candida strains were sensitive to periodate oxidation, whereas the Fusobacterium strains were stable to this treatment. All coaggregations occurred in the presence of saliva and appeared stronger than in buffer. These data suggest that the coaggregations involve either a protein or glycoprotein on the Fusobacterium surface, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Candida. These observations expand the known range of intergeneric coaggregations occurring between human oral microbes and indicate that coaggregation of C. albicans and Fusobacterium species may be an important factor in oral colonization by this yeast. The authors believe this to be the first description of coaggregation concerning a carbohydrate component on the yeast cell and a protein component on the oral bacterial cell.

Bacterial Adhesion↗
PubMed2004

Oral Candida isolates in patients undergoing radiotherapy for head and neck cancer: prevalence, azole susceptibility profiles and response to antifungal treatment.

Oral pseudomembranous candidiasis and mucositis were assessed in 39 patients receiving a total dose of 39-70 Gy radiotherapy for head and neck cancer. Mucositis was scored using the Radiation Therapy Oncology Group criteria, and oral candidiasis was diagnosed on the basis of clinical evaluation and quantitative laboratory findings. Radiation-induced mucositis was observed in 9/39 patients. Only 3/39 patients discontinued radiotherapy due to acute severe mucosal effects. Candidiasis (colony-forming units 35 to > or = 60/lesion) associated with mucositis was diagnosed in 30/39 patients: the most frequent aetiology of the infection was Candida albicans (n = 23), followed by Candida glabrata (n = 3), Candida krusei (n = 2), Candida tropicalis (n = 1) and Candida kefyr (n = 1). Patients with confirmed oral pseudomembranous candidiasis were treated with either fluconazole 200 mg/day or itraconazole 200 mg/day for 2 weeks. Clinical improvement and concomitant negative Candida cultures (mycologic cure) were the criteria determining a response to antifungal treatment. Etest revealed very low voriconazole MICs (0.004-0.125 microg/ml) for all isolates, and fluconazole resistance for eight C. albicans strains (MIC > 64 microg/ml) and for the C. krusei isolates (MIC > 32 microg/ml). The same strains showed itraconazole susceptibility dose dependence (MIC 0.5 microg/ml). Despite the itraconazole susceptible dose dependent MIC readings, all patients with oral pseudomembranous candidiasis caused by these strains responded to antifungal treatment with 200 mg/day itraconazole. Oral mycologic surveillance of patients undergoing radiotherapy for head and neck malignancies and susceptibility testing of isolates may be indicated in cases with mucositis-associated confirmed oral pseudomembranous candidiasis to ensure prompt administration of targeted antifungal treatment. On the basis of the low MIC values found, clinical evaluation of voriconazole is indicated for management of oral pseudomembranous candidiasis refractory to other azoles.

Adult↗