Case report. Disseminated infection of Blastoschizomyces capitatus in a patient with acute myelocytic leukaemia

Blastoschizomyces capitatus infection in a 48-year-old man with acute myelocytic leukaemia is reported. A multiorgan involvement and fulminant course of the fungal infection resulted in the patient's death despite fluconazole prophylaxis, therapy with amphotericin B and administration of granulocyte colony-stimulating factor. Predisposing factors to the infection, clinical relevance of surveillance strains and in vitro antifungal susceptibility testing are discussed.     

In-vitro comparative activity of fluconazole and other antifungal agents against Blastoschizomyces capitatus

Blastoschizomyces capitatus represents an emerging fungal pathogen in acute leukemia patients. The susceptibility to amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole of nine clinical isolates was evaluated. A specific medium (high resolution medium) was used for testing fluconazole. This agent and 5-fluorocytosine were at least four- to eight-fold more active than amphotericin B and ketoconazole against all isolates but one.     

In vitro antifungal activity of amphotericin B and 11 comparators against Aspergillus terreus species complex

Aspergillus terreus infections are difficult to treat because of the intrinsic resistance to amphotericin B, and higher mortality compared to infections caused by other Aspergillus species. The aim of the present study was to determine the in vitro antifungal activity of amphotericin B and 11 comparators against clinical (n = 36) and environmental (n = 45) A. terreus isolates. In vitro antifungal susceptibility was performed using the CLSI M38‐A2 procedure. Amphotericin B exhibited the highest MICs (MIC range, 0.125‐4 μg/mL; MIC₉₀, 2 μg/mL), followed by terbinafine (MIC range, 0.002‐1 μg/mL; MIC₉₀, 1 μg/mL). Only one isolate (1/81) showed amphotericin B MIC above the epidemiologic cut‐off value (ECV; 4 μg/mL). None of the isolates had a MIC of ≥ ECV for voriconazole, itraconazole and posaconazole. The reasons for the difference in amphotericin B susceptibility patterns between studies remain unknown. The genetic and species diversity, clinical, environmental and ecological factors in Terrei section on various amphotericin B susceptibility profiles in different countries should be considered more as the main reasons associated with these differences.     

Activity of terbinafine against serious fungal pathogens

Although primarily indicated for dermatophyte infections, the allylamine terbinafine is active in vitro against a broad spectrum of filamentous and dimorphic fungi, in most cases with a primary fungicidal action. Using the standard NCCLS M27-A assay, recent studies confirmed the high activity of terbinafine against dematiaceous fungi and other medically important moulds such as Aspergillus and Penicillium marneffei. Terbinafine displayed a geometric mean MIC of 1.4 micrograms/ml against Candida albicans (n = 259) and has significant in vitro activity against other species of Candida, Cryptococcus, Trichosporon and Blastoschizomyces. As an approach to treatment of refractory infections, interactions of terbinafine with azoles and other agents are being investigated. Terbinafine was synergistic with azoles (and in some cases amphotericin B) against Candida species, Trichosporon beigelii, Aspergillus species, Pseudallescheria boydii and Scopulariopsis brevicaulis, some of which were unresponsive to any drug used singly. Terbinafine combined with fluconazole showed potent synergy against fluconazole- and multidrug-resistant C. albicans isolates. In conclusion, recent in vitro data suggest that terbinafine, either alone or in combination with other antifungal drugs, has potential in the therapy of a range of more severe fungal infections, in addition to its current widespread use against dermatomycoses.     

In vitro activities of new and conventional antimycotics against fluconazole-susceptible and non-susceptible Brazilian Candida spp. isolates

The substantial increase in the rate of azole resistant Candida spp. yeast infections has become a serious treatment problem requiring new and more active antifungal agents. In this study, the in vitro activities of ravuconazole and albaconazole were compared with those of amphotericin B, flucytosine, itraconazole and fluconazole against 162 Brazilian isolates of Candida spp. from which 48 isolates had previously shown lower susceptibility or resistance to fluconazole. Ravuconazole susceptibility ranged from 84.6% (Candida albicans) to 100% for other species and albaconazole MIC(90) was < or =1.0 microg ml(-1) for all the species emphasising the potent activity of these triazoles. To our knowledge this is the first study evaluating the susceptibility of C. dubliniensis to albaconazole.     

Blastoschizomyces capitatus infection in acute leukemia patients

Blastoschizomyces capitatus (BC), a filamentous fungus of genus Trichosporum, is as an important opportunistic pathogen in the compromised host. Within the past 10 years, 47 cases of BC infection have been published. Most of the patients had acute leukemia (AL) or related disorders and had received chemotherapy treatment. Due to BC's resistance to currently used antifungal agents, this infection represents a therapeutic challenge and serious complication in the treatment of hematology malignancies. Here we report our experience with BC infection in four patients with acute leukemia or related disorders.     

Antifungal susceptibility testing of a 10-year collection of Candida spp. isolated from patients with candidemia

Nosocomial yeast infections have increased significantly worldwide and especially in surgical and intensive care unit (ICU) patients. Although Candida species have various degrees of susceptibility to frequently used drugs, antifungal resistance is rare. A ten-year retrospective surveillance of candidemia was carried out in a University Hospital of Southern Italy. The aim of this study was the determination of Candida bloodstream infections (BSI) and central venous catheter (CVC)- related episodes, prevalence and in vitro susceptibility. 320 candidemia episodes were registered and 374 yeasts collected. Etest and Sensititre methods were used to test the isolates' susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole. The results were compared with those of CLSI reference broth microdilution method. Most yeasts were susceptible to all antifungal drugs, with the exception of C. Glabrata susceptibility to triazoles and C. tropicalis to fluconazole and voriconazole. As expected, C. parapsilosis isolates were generally associated with higher echinocandin minimum inhibitory concentrations (miCs) than the other Candida species. This study confirms the different antifungal susceptibility patterns among species, and underlines the need to perform antifungal susceptibility testing of clinically relevant yeasts.     

Geotrichosis of oral mucosa

Summary. A livid, sharply defined enanthema of the oral mucosa with ulcerations on the soft palate in a patient presenting with de novo acute myeloid leukaemia with prolonged, therapy-induced granulocytopenia (lt 0.5 nl^-1 for 113 days!) was diagnosed as geotrichosis. Geotrichum capitatum was identified both in vivo and in vitro. Pneumonic infiltrates in the upper lobes of both lungs were treated with amphotericin B infusions. Healing of the aforementioned enanthema was only achieved after addition of 5-fluorocytosine to therapy. Susceptibility determinations with several Geotrichum capitatum isolates led to the conclusion that amphotericin B was unsuitable as a therapeutic agent in this case. 5-Fluorcytosine and itraconazole exhibited superior antifungal and antimycotic activity.
Zusammenfassung. Ein livides, scharf begrenztes Enanthem der Mundschleimhaut mit Ulzerationen am weichen Gaumen bei einer de novo akuten myeloischen Leukämie mit extrem langer, therapiebedingter Granulozytopenie (lt 0.5 nl^-1über 113 Tage!) wird als Geotrichose angesehen. Geotrichum capitatum wurde in vivo und in vitro nachgewiesen. Pneumonische Infiltrate in beiden Lungenoberlappen waren Anlaß zu einer Infusionstherapie mit Amphotericin B. Eine Abheilung des obengenannten Enanthems wurde allerdings erst nach Umstellung der Therapie auf 5–Fluorcytosin-Infusionen erzielt. Resistenzbestimmungen mit mehreren Isolaten hinterließen den Eindruck, daß Amphotericin B als Therapeutikum hier nicht geeignet war. 5–Fluorcytosin und Itraconazol zeigten einen besseren antimyzetischen Effekt und antimykotische Wirksamkeit.     

Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review

Onychomycosis is a common superficial fungal infection, which usually caused by dermatophytes, yeast and non‐dermatophytic moulds. Recently, we isolated a Rhodotorula minuta isolate from a 15‐year‐old immunocompetent girl student in Hangzhou (China) that was identified using microscopy, culture morphology, histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, itraconazole, voriconazole and 5‐flvoriconaz but that it appeared to be dose‐dependent susceptible to fluconazole(MIC = 16 μg/ml). Furthermore, the effective result of therapy with itraconazole against R. minuta was consistent with that of susceptibility tests.     

Comparison of Etest with the broth microdilution method in susceptibility testing of yeast isolates against four antifungals

A comparative evaluation of the Etest and the broth microdilution methods for antifungal susceptibility testing of 102 clinical yeast isolates against amphotericin B, fluconazole, itraconazole, and ketoconazole was conducted. The agreements between the Etest and the broth microdilution methods were 93.1% for amphotericin B 85.2% for ketoconazole, 82.3% for itraconazole and 79.4% for fluconazole. These results suggest that the Etest approach to antifungal susceptibility testing may be a viable alternative to the NCCLS reference methods for testing yeasts, but that further evaluations are needed.     

In- Vitro Comparative Activity of Fluconazole and Other Antifungal Agents Against Blastoschizomyces capitatus

Summary

Blastoschizomyces caphatus represents an emerging fungal pathogen in acute leukemia patients. The susceptibility to amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole of nine clinical isolates was evaluated. A specific medium (high resolution medium) was used for testing fluconazole. This agent and 5-fluorocytosine were at least four- to eightfold more active than amphotericin B and ketoconazole against all isolates but one.     

Disseminated Geotrichum capitatum Infection in a Patient with Acute Myeloid Leukemia: Disseminierte Geotrichum capitatum-Infektion bei einem Patienten mit akuter myeloischer Leukamie

A case of invasive Geotrichum capitatum infection is reported; a young patient had an acute leukemia for which he received a chemotherapy, and presented sepsis with blood cultures for Geotrichum capitatum, namely Dipodascus spicifer; this pathogen only described in cactus rot, is responsible for the first case of a human disseminated infection reported in literature. Then he developed a splenic and epididymic infection, with positive cultures for Geotrichum capitatum after splenectomy and castration. Treatment with amphotericin B and itraconazole was started with low minimal inhibitory concentration (0.1 microgram/ml). The patient died of massive hemoptisis. Autopsy findings demonstrated a lung, brain and kidneys seeding.     

Emergence of resistance to amphotericin B and triazoles in Candida glabrata vaginal isolates in a case of recurrent vaginitis

Emergence of resistance to triazoles and amphotericin B in Candida glabrata vaginal isolates is documented by Etest. During the 18-month follow-up of a case of vaginitis, 14 consecutive isolates of C. glabrata were examined. The isolates exhibited development of in vitro resistance beginning with itraconazole (>32 microg/ml), followed by fluconazole (>256 microg/ml), amphotericin B (>32 microg/ml), and voriconazole (>32 microg/ml). The DNA sequence analyses and finger printing of the isolates strongly suggest that our patient remained colonized with a single strain. The report underscores the propensity of C. glabrata to acquire resistance during antifungal therapy and the importance of susceptibility testing in the management of infections caused by this species.     

Candida rugosa in immunocompromised infection. Case reports, drug susceptibility, and review of the literature

Candida rugosa was isolated from two patients. One patient had acute leukemia and developed invasive disease due to this yeast on two occasions while granulocytopenic. Her infection was eventually cured after treatment with amphotericin B. In another immunocompromised patient, the yeast was isolated from the sputum in the presence of a pulmonary infiltrate, but there was no other evidence for a pathogenic role. Antifungal susceptibility testing of the first patient's isolate and three environmental isolates showed all four to be susceptible to amphotericin B, miconazole, and flucytosine, and only the patient isolate was resistant to ketoconazole. These results suggest possibilities for therapy in future encounters. It appears that C. rugosa, a common pathogen in cattle, can be pathogenic in humans under the appropriate circumstances.     

In vitro susceptibility of Cryptococcus neoformans clinical isolates from Egypt to seven antifungal drugs

The in vitro susceptibility of 29 clinical isolates of Cryptococcus neoformans to fluconazole, miconazole, itraconazole, ketoconazole, flucytosine, nystatin and amphotericin B was tested by broth and colorimetric microdilution methods. Most of the isolates showed uniform patterns of susceptibility to the used antifungal agents. Only three isolates exhibited resistance [fourfold or greater rise in the minimum inhibitory concentrations (MICs)] to the tested antifungal drugs. The MIC50 and MIC90 were 0.5-8 mg l(-1) for 5-flucytosine, 0.2-8.25 mg l(-1) for nystatin, 0.5-16 mg l(-1) for fluconazole and 0.2-12.5 mg l(-1) for miconazole. However, MIC50 and MIC90 were in narrow range for the clinical yeast isolates in both methods used and showed 0.5-1 mg l(-1) for amphotericin B and 0.016-0.25 mg l(-1) for both ketoconazole and itraconazole. The combination of fluconazole plus flucytosine showed greater synergistic and fungicidal activity compared with that of fluconazole plus amphotericin B or the use of individual drugs.     

First neonatal case of fungaemia due to Pseudozyma aphidis and a global literature review

The Ustilaginomycetous basidiomycete yeast, Pseudozyma aphidis has recently been implicated in potentially fatal disorders ranging from subcutaneous mycoses to disseminated infections. Till date a solitary case of P. aphidis fungaemia in a paediatric patient has been reported. We present a case of fungaemia due to P. aphidis in a rhesus factor‐isoimmunised, low‐birth‐weight neonate. The isolate was identified by sequencing the D1/D2 domain of the LSU region. Antifungal susceptibility of the isolate revealed susceptibility to amphotericin B, voriconazole, itraconazole, isavuconazole and posaconazole. It had high minimum inhibitory concentrations of fluconazole and was resistant to flucytosine and echinocandins. Consequently, the patient was successfully treated with intravenous amphotericin B. Although the source of infection could not be traced, as the neonate developed fungaemia on the first day of life, it could possibly be from the maternal urogenital tract or intrahospital transmission. A review of previously published cases revealed that risk factors for invasive Pseudozyma spp. infections were similar to those previously reported for non‐albicans Candida spp. Pseudozyma species are underreported due to the difficulty of identifying this rare yeast pathogen by commercial identification systems. Considering that Pseudozyma spp. cause invasive fungal infections globally and are resistant to flucytosine, fluconazole and echinocandins, this pathogen assumes a greater clinical significance.     

Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates.

The in vitro susceptibilities of 183 clinical yeast isolates to sertaconazole (STZ) were compared to their susceptibilities to clotrimazole (CTZ), econazole (ECZ), ketoconazole (KTZ), miconazole (MNZ), fluconazole (FLZ), itraconazole (ITZ), tioconazole (TCZ), amphotericin B (AMB) and flucytosine (5FC) by using a commercial agar diffusion method. Strains were isolated from vaginal and other superficial clinical samples (18 species of Candida and five strains belonging to other yeast genera). Only one strain (0.5%) was resistant to STZ out of 87.4% of susceptible strains (n=160). The percentage of susceptible strains was higher than those obtained with the other agents evaluated and the percentage of resistant strains was lower than for most of the other antifungals. The pattern of susceptibility of C. albicans to STZ, TCZ, ITZ and CLZ was similar and superior to the pattern of susceptibility of this species to MNZ, ECZ, FLZ, 5FC and KTZ. C. dubliniensis was more susceptible to STZ, MNZ, MNZ, FLZ, ITZ, CLZ than to TCZ, ECZ, 5FC, AMB or KTZ. Ten susceptible strains to STZ were resistant to FLZ and one strain was resistant to ITZ. The overall antifungal activity of STZ in vitro against a wide range of clinically important yeasts from vaginal and cutaneous samples indicates the therapeutic potential of this agent for the treatment of infections caused by these fungi. However, the activity of STZ and the clinical value of in vitro data need to be verified in human clinical trials.     

In vitro activities of voriconazole (UK-109, 496), fluconazole, itraconazole and amphotericin B against 132 non-albicans bloodstream yeast isolates (CANARI study)

The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections.     

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

BACKGROUND: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.     

Comparative evaluation of Fungitest-, Neo-Sensitabs- and M27T-NCCLS broth microdilution methods for antifungal drug susceptibility testing of Candida species and Cryptococcus neoformans.

Two commercial antifungal susceptibility testing systems (Fungitest and Neo-Sensitabs) were compared with the M27T-NCCLS reference broth microdilution method using one hundred isolates of Candida sp. and Crptococcus neoformans. Six different antifungal drugs were tested: amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and miconazole. The overall agreement between the Fungitest and the reference methods was much better than between the Neo-Sensitabs and the reference methods: the agreement for the Fungitest ranged from 100% for amphotericin B to 76.7% for itraconazole whereas for the Neo-Sensitabs, it ranged from 90.4% for amphotericin B to 36% for ketoconazole. For the total number of tests performed with Neo-Sensitabs, there were 37.8% of discrepancies with the reference method whereas for the tests performed with Fungitest, there was only 16.5% of discrepancies. Major discrepancies, defined as results that classified an isolate as susceptible by one method and resistant by another, occurred in 21 cases for the Neo-Sensitabs test and only in four cases with the Fungitest, namely 0.6% of the cases. We conclude that the Fungitest method constitutes a simple and reliable procedure for antifungal drug susceptibility testing.