Fungemia due to Candida guilliermondii in a pediatric and adult population during a 12-year period.

Candida guilliermondii fungemia is usually described in adults with hematologic malignancies, but in children, only 2 episodes have been published. From 1995 to 2006, 7 episodes (5 in children) were detected in our hospital. Molecular typing excluded a common infection source. C. guilliermondii fungemia may occur in children with underlying conditions other than cancer.

Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species.

Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104 Candida parapsilosis, 14 C.glabrata, 13 C.tropicalis, 15 C.krusei, and 19 C.albicans) and 36 C.dubliniensis from oropharyngeal infections. Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method. MFCs (> or =99.9% killing) were obtained following MIC determination (inoculum size, 10(4) CFU/ml) by seeding the entire volume of all clear wells. The best fungicidal activity was for C. albicans, (MFC90 1 microg/ml) and the lowest for C.parapsilosis, C.tropicalis and C.glabrata (MFC90 16 microg/ml). Although MFCs were > or =16x MIC for some isolates, including C. glabrata, the overall MFCs were > or =2x MICs. However, major differences between MICs and MFCs were observed for C.parapsilosis and C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC > or =32MIC). MFCs for C.tropicalis and C. glabrata were > or =2 microg/ml. By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for Candida spp.

The C-terminal antibody binding domain of Candida albicans mp58 represents a protective epitope during candidiasis.

The 58-kDa surface mannoprotein of Candida albicans (mp58) elicits strong antibody responses during infection. Epitope mapping with sera from patients with candidiasis and control individuals indicated the presence of multiple IgG-reactive continuous epitopes on the protein, expanding both the amino- and carboxy-terminal domains and several internal regions. These immunoreactive regions were similar to the ones previously identified using sera from immunized animals. Two of the epitopic regions (including the C-terminal domain) showed increased reactivity with antibodies present in sera from patients with candidiasis as compared to control individuals. Patients who survived the infection displayed increased antibody reactivity towards the C-terminal epitope as compared to those succumbing to candidiasis. A monoclonal antibody directed towards this epitopic region conferred protection in serum therapy experiments in a murine model of hematogenously disseminated candidiasis. Together, these observations indicate the carboxy-terminal antibody binding domain of C. albicans mp58 represents a protective epitope during candidiasis.

Kinetic patterns of Candida albicans germ tube antibody in critically ill patients: influence on mortality.

The influence of kinetic patterns of Candida albicans germ tube antibodies (CAGTA) on mortality was analyzed in six intensive care units. Statistically significant lower mortality rates were found in patients with patterns of increasing CAGTA titers who had been treated with antifungal agents. Thus, antifungal treatment should be considered when CAGTA titers are increasing in critically ill patients.

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.

Voriconazole in the management of nosocomial invasive fungal infections.

Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug-drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients.

A proteomic-based approach for the identification of Candida albicans protein components present in a subunit vaccine that protects against disseminated candidiasis.

Candidiasis has become a prevalent infection in different types of immunocompromised patients. The cell wall of Candida albicans plays important functions during the host-fungus interactions. Cell wall (surface) proteins of C. albicans are major elicitors of host immune responses during candidiasis, and represent candidates for vaccine development. Groups of mice were vaccinated subcutaneously with a beta-mercaptoethanol (beta-ME) extract from C. albicans containing cell wall proteins. Vaccinated mice were then infected with a lethal dose of C. albicans. Increased survival and decreased fungal burden were observed in vaccinated mice as compared to a control group, and 75% of vaccinated mice with the beta-ME extract survived this otherwise lethal infection. We used a proteomic approach (2-DE followed by immunoblotting) to demonstrate a complex polypeptidic pattern associated with the beta-ME extract used in the vaccine formulation and to detect immunogenic components recognized by antibodies in immune sera from vaccinated animals. Reactive protein spots were identified by MALDI-TOF-MS and searches in genomic databases. As a conclusion, vaccination strategies using C. albicans cell wall proteins induce protective responses. These antigens can be identified by proteomic approaches and may be used as components of subcellular vaccines against candidiasis.

Synergistic activities of fluconazole and voriconazole with terbinafine against four Candida species determined by checkerboard, time-kill, and Etest methods.

The in vitro activities of fluconazole or voriconazole plus terbinafine were evaluated against 20 Candida isolates by the checkerboard, time-kill, and Etest methods. Synergism (C. albicans, C. glabrata, and C. tropicalis) and indifference (C. krusei) were observed. Correlation among methods was good. The Etest is a suitable method to determine drug interactions.

[Epidemiology of candidemia in Spain - Multicenter study] / Estudio multicéntrico sobre la epidemiología de las candidemias en España.

The results of the epidemiological study on candidemias with the highest number of cases carried out in Spain is presented. This study is included in the Epidemiological Survey of Candidemia in Europe supported by the ECMM in which another five countries take part. In the Spanish study, 19 hospitals participated, 290 candidemia episodes were analysed (80 in children under 15 years and 210 in adults), 293 strains of yeasts being isolated. Both in children and in adults, the risks factors more frequently observed were the intravenous catheter and previous antibiotic therapy. In adults, the most habitual underlying disease was the solid tumor and, in children, hematological diseases. Candida albicans was the most prevalent species isolated in adults (46.1%) and Candida parapsilosis in children (50%). As part of the therapy, the intravenous line was removed and antifungal treatment was prescribed to 74% and 92.5% of children, respectively and to 43.8% and 73.8% of adults. The antifungal agent of election in adults was fluconazole (54.8%) and liposomal amphotericin B (58.1%) in children. The global mortality of the study was 38.9%, which for ages was major in adults (41.4%) than in children (38.7%). The geographical distribution of the isolated species was homogeneous, C. albicans being the predominant species, with the exception of Galicia and Extremadura where C. parapsilosis was the most frequent.

Patterns of amphotericin B killing kinetics against seven Candida species.

In a previous study tolerance to amphotericin B (AMB) was found among Candida parapsilosis and C. dubliniensis strains by seeding the whole volumes of wells used for MIC determinations, and minimum fungicidal concentrations (MFC) for non-C. albicans Candida strains were demonstrated to be above the levels safely achievable in serum. As an extension of that study, we performed time-kill assays with 26 blood culture isolates (6 C. albicans, 5 C. parapsilosis, 5 C. krusei, 4 C. glabrata, 3 C. lusitaniae, and 3 C. tropicalis isolates), 3 oropharyngeal C. dubliniensis isolates, 3 AMB-susceptible isolates (ATCC 90028, ATCC 22019, ATCC 6254), and 6 AMB-resistant isolates (ATCC 200955, ATCC 200956, ATCC 200950, ATCC 200951, ATCC 200952, ATCC 200953) using RPMI 1640 medium and 0.12 to 32 microg of AMB per ml and determined the numbers of CFU per milliliter at 0, 2, 4, 8, 12, 24, and 48 h. MFCs and time-kill patterns were species specific (MFCs, < or =1 microg/ml for all C. dubliniensis and C. albicans isolates except AMB-resistant strain ATCC 200955; MFCs, 2 to >16 microg/ml for the other isolates). The times required to reach the fungicidal endpoint (99.9% killing) at four times the MIC were 2 h for C. albicans and C. dubliniensis, 16 h for C. glabrata, 24 h for C. parapsilosis and C. lusitaniae, and > or =40 h for C. tropicalis and C. krusei. The killing rate increased as the AMB concentration was increased up to 2 microg/ml. The highest killing rates were achieved for C. albicans, C. dubliniensis, and C. lusitaniae, while viable C. tropicalis, C. krusei, and C. parapsilosis cells were present after 48 h (MICs, < or =2 microg/ml) when AMB was used at 2 microg/ml. Time-kill curves and MFCs can detect viable cells after 48 h when AMB is used at > or =2 microg/ml. The failure of AMB treatment could be due to its poor killing activity against some species at the concentrations reached in patients' serum.