amphotericin-b and Chromoblastomycosis

In the past 20 years, there has been a marked increase in the number of reported cases of meningitis and brain abscess due to fungi and yeasts. This increase is due in part to better diagnostic techniques and greater awareness of the possibility of fungal invasion of the nervous system; but the increase can also be attributed to a growing pool of severely compromised hosts, many of whom are undergoing treatment with adrenal glucocorticoids or immunosuppressive agents. The diagnosis and treatment of aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, infections caused by dematiaceous fungi, histoplasmosis, paracoccidioidomycosis, petriellidosis, and sporotrichosis, as well as relatively rare infections of the central nervous system caused by other fungi, are discussed. The efficacy of amphotericin B and 5-fluorocytosine in the treatment of CNS fungal and yeast infections is also evaluated.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Central Nervous System Diseases; Chromoblastomycosis; Cladosporium; Coccidioidomycosis; Cryptococcosis; Female; Fungi; Histoplasmosis; Humans; Male; Meningitis; Meningoencephalitis; Middle Aged; Mucormycosis; Mycoses; Paracoccidioidomycosis; Phialophora; Sporotrichosis

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Imidazoles; Ketoconazole; Lung Diseases, Fungal; Miconazole; Mycoses; Nausea; Piperazines; Vomiting

Flucytosine is a systemic antifungal drug that is readily absorbed from the gastrointestinal tract. The most clearly documented therapeutic effect has been in cryptococcosis, candidiasis, and chromomycosis. An important limitation of the use of flucytosine in all three diseases has been drug resistance arising during therapy. The addition of low-dose, intravenous amphotericin B to flucytosine therapy of cryptococcosis has appeared to decrease the frequency of secondary flucytosine resistance. In addition, the two drugs have an additive or slightly synergistic effect against flucytosine susceptible isolates of Cryptococcus and Candida. The combination is probably the treatment of choice in cryptococcal meningitis and offers promise in the therapy of systemic candidiasis and nonmeningeal cryptococcosis.

Topics: Amphotericin B; Candidiasis; Chromoblastomycosis; Cryptococcosis; Cytosine; Drug Therapy, Combination; Flucytosine; Mycoses

Topics: Actinomycosis; Adolescent; Adult; Amphotericin B; Animals; Aspergillosis; Basidiomycota; Blastomycosis; Candidiasis; Cephalosporins; Child; Chromoblastomycosis; Coccidioidomycosis; Conjunctiva; Cryptococcosis; Drug Synergism; Eye Diseases; Female; Fungi; Geotrichosis; Guinea Pigs; Histoplasmosis; Humans; Male; Mucor; Mycetoma; Mycoses; Natamycin; Nystatin; Penicillium; Pityriasis; Rabbits; Rhinosporidiosis; Sporotrichosis; Tinea

The author proposes a new method of treatment for chromoblastomycosis, using the association of two drugs of confirmed therapeutic activity: amphotericin B and 5-fluorocytosine. The aim was to obtain a synergistic action against the causative fungus. The method consists of the following: 50 mg. of amphotericin B is injected i.v. every other day --three times a week-- for three months. Total dosis: 36 ampoules. 5-fluorocytosine is simultaneously given orally --6 tablets of 500 mg. a day-- for three months in a total dosis of 540 tablets or 270 g. Seventeen patients were treated in this way up to now. Six interrupted the treatment on account of several reasons unrelated to treatment. The other 11 that completed this schedule, obtained clinical and histological cure. All were followed-up. No evidence of relapse was seen, even after 27 months of control. The safety of this method of treatment was demonstrated by the low incidence of side effects as inappetence, lassitude, nausea and weight loss. In these circumstances the discontinuance of the drugs for some days was sufficient to resume the treatment. Apparently this therapeutic schedule is the most effective up to now. It has the advantage of not causing resistance and by utilizing low concentrations of the drugs, protecting the patient against risks of toxicity.

Topics: Adult; Amphotericin B; Chromoblastomycosis; Clinical Trials as Topic; Cytosine; Drug Evaluation; Drug Therapy, Combination; Female; Flucytosine; Humans; Injections, Intravenous; Male; Middle Aged; Tablets

Topics: Amphotericin B; Antifungal Agents; Chromoblastomycosis; Humans; Itraconazole; Microbial Sensitivity Tests; Terbinafine

Fonsecaea monophora, which is very similar to Fonsecaea pedrosoi in morphological features, has been commonly misdiagnosed as F. pedrosoi. Like F. pedrosoi, F. monophora has been also identified as a predominant pathogen of Chromoblastomycosis (CBM). Melanin has been recognized as a virulence factor in several fungi, however, it is still largely unknown about the biological role of melanin and how melanin is synthesized in F. monophora. In this study, we identified two putative polyketide synthase genes (pks), AYO21_03016 (pksA) and AYO21_10638, by searching against the genome of F. monophora. AYO21_03016 and AYO21_10638 were further targeted disrupted by Agrobacterium tumefaciens-mediated transformation (ATMT). We discovered that pksA gene was the major polyketide synthase required for melanin synthesis in F. monophora, rather than AYO21_10638. Phenotypic analysis showed that, knocking out of the pksA gene attenuated melanogenesis, growth rate, sporulation ability and virulence of F. monophora, as compared with wild-type and complementation strain (pksA-C). Furthermore, the ΔpksA mutant was confirmed to be more sensitive to the oxidative stress, extreme pH environment, and antifungal drugs including itraconazole (ITC), terbinafine (TER), and amphotericin B (AMB). Taken together, these findings enabled us to comprehend the role of pksA in regulating DHN-melanin pathway and its effect on the biological function of F. monophora.

Topics: Amphotericin B; Antifungal Agents; Bacterial Proteins; Chromoblastomycosis; Fonsecaea; Gene Deletion; Genome, Fungal; Humans; Itraconazole; Melanins; Polyketide Synthases; Spores, Fungal; Terbinafine

Topics: Amphotericin B; Antifungal Agents; Chromoblastomycosis; Cytoreduction Surgical Procedures; Humans; Itraconazole; Microbial Sensitivity Tests; Terbinafine

Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinafine are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinafine. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinafine with the other four antifungals. The combined effect of terbinafine and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 μg/mL, 2 μg/mL, 1 μg/mL, 4 μg/mL and 8 μg/mL, respectively. The combination of terbinafine and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinafine and the other four antifungal drugs. The combination of terbinafine and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinafine (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinafine monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinafine and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; Drug Synergism; Drug Therapy, Combination; Female; Humans; Microbial Sensitivity Tests; Middle Aged; Terbinafine

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Topics: Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; Exophiala; Microbial Sensitivity Tests; Phialophora; Terbinafine

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Topics: Administration, Topical; Amphotericin B; Antifungal Agents; Bronchoscopy; Chromoblastomycosis; Female; Humans; Lung; Lung Diseases, Fungal; Lung Transplantation; Middle Aged; Postoperative Complications; Scedosporium

Chromoblastomycosis (CBM) is a difficult-to-treat chronic subcutaneous mycosis. In Brazil, the main agent of this disease is Fonsecaea pedrosoi, which is phenotypically very similar to other Fonsecaea species, differing only genetically. The correct species identification is relevant since different species may differ in their epidemiologic aspects, clinical presentation, and treatment response.. Partial sequencing of the internal transcribed spacer (ITS) was used to identify twenty clinical isolates of Fonsecaea spp. Their in vitro antifungal susceptibility was determined using the broth microdilution method, according to the M38-A2 protocol. Amphotericin B (AMB), flucytosine (5FC), terbinafine (TRB), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), posaconazole (POS), voriconazole (VRC), ravuconazole (RVC), caspofungin (CAS), and micafungin (MFG) were tested. The association between ITC/TRB, AMB/5FC, and ITC/CAS was studied by the checkerboard method to check synergism. The available patients' data were correlated with the obtained laboratory results. Fonsecaea monophora (n = 10), F. pedrosoi (n = 5), and F. nubica (n = 5) were identified as CBM' agents in the study. TRB and VRC were the drugs with the best in vitro activity with minimal inhibitory concentrations (MIC) lower than 0.25 mg/L. On the other hand, FLC, 5FC, AMB, and MFG showed high MICs. The AMB/5FC combination was synergistic for three F. monophora strains while the others were indifferent. Patients had moderate or severe CBM, and ITC therapy was not sufficient for complete cure in most of the cases, requiring adjuvant surgical approaches.. F. monophora, the second most frequent Fonsecaea species in South America, predominated in patients raised and born in Rio de Janeiro, Brazil, without cerebral involvement in these cases. TRB, VRC, and the AMB/5FC combination should be further investigated as a treatment option for CBM.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Ascomycota; Brazil; Caspofungin; Chromoblastomycosis; DNA, Fungal; DNA, Intergenic; Echinocandins; Female; Humans; Itraconazole; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Voriconazole

Chromoblastomycosis is a chronic granulomatous disease caused frequently by fungi of the Fonsecaea genus. The objective of this study was the phenotypic and molecular identification of F. pedrosoi strains isolated from chromoblastomycosis patients in Mexico and Venezuela. Ten strains were included in this study. For phenotypic identification, we used macroscopic and microscopic morphologies, carbohydrate assimilation test, urea hydrolysis, cixcloheximide tolerance, proteolitic activity and the thermotolerance test. The antifungal activity of five drugs was evaluated against the isolates. Molecular identification was performed by sequencing the internal transcribed spacer (ITS) ribosomal DNA regions of the isolated strains. The physiological analysis and morphological features were variable and the precise identification was not possible. All isolates were susceptible to itraconazole, terbinafine, voriconazole and posaconazole. Amphotericin B was the least effective drug. The alignment of the 559-nucleotide ITS sequences from our strains compared with sequences of GenBank revealed high homology with F. pedrosoi (EU285266.1). In this study, all patients were from rural areas, six from Mexico and four from Venezuela. Ten isolates were identified by phenotypic and molecular analysis, using ITS sequence and demonstrated that nine isolates from Mexico and Venezuela were 100% homologous and one isolate showed a small genetic distance.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; DNA, Ribosomal Spacer; Female; Humans; Itraconazole; Male; Mexico; Microbial Sensitivity Tests; Middle Aged; Mitosporic Fungi; Molecular Sequence Data; Phenotype; Sequence Analysis, DNA; Skin; Venezuela; Voriconazole

Chromoblastomycosis is a chronic mycosis that affects the skin and subcutaneous tissues caused by several genera of dematiaceous fungi. There is not a treatment of choice. Thus, tools that help guide clinical practice are fundamental. In this sense, antifungal activity tests in vitro could be useful. However, trials with chromoblastomycosis agents are scarce. The aim of this study was to evaluate both the in vitro susceptibility of 60 chromoblastomycosis agents to five antifungals and the combination of amphotericin B (AMB) and terbinafine (TRB). TRB, itraconazole (ITZ) and ketoconazole (KTZ) were, in this order, the drugs which showed better activity against the chromoblastomycosis agents. The less active drugs were voriconazole (VRZ) and AMB. The more differentiated group was Exophiala spinifera. Cladophialophora carrionii and Fonsecaea spp. are significantly more susceptible to KTZ than Phialophora verrucosa, whereas C. carrionii is significantly more sensitive to VRZ than P. verrucosa and E. spinifera. Assays in this direction allow the knowledge of the susceptibility of the causative agents which may help the management of patients with this disease. This study includes the largest number of these agents and of genera found in the literature.

Topics: Amphotericin B; Animals; Antifungal Agents; Chromoblastomycosis; Drug Synergism; Fungi; Naphthalenes; Terbinafine

Chromomycosis is a chronic fungal skin infection that generally presents in the form of verrucous or vegetative lesions on uncovered areas of skin. We report an unusual case of generalised chromomycosis due to Phialophora verrucosa.. A 42-year-old town-dwelling housewife was hospitalised for erythematous keratotic nodules on the arm showing sporotrichoid distribution, associated with a crusted ulcerative lesion on the homolateral index finger, as well as subcutaneous papulonodular lesions. In places, the lesions on the patient's back presented an umbilical and molluscoid appearance. The patient had suffered no previous injuries and had not visited any areas in which leishmaniasis is endemic. Her history included insulin-dependent diabetes. Screening for Leishman bodies was negative. Histopathological analysis of the skin biopsy revealed an epithelioid giant-cell granuloma with no caseous necrosis. The mycological study demonstrated the presence of fumagoid bodies and P. verrucosa was isolated. Treatment with terbinafine was initially given, followed by clarithromycin, but in the absence of any improvement, the patient was readmitted to hospital and is currently on itraconazole and amphotericin B.. The novel features of our case comprise the clinical aspect of chromomycosis, the extent of the lesions, their unusual site on the back and upper limbs, and the isolation of a rare species, P. verrucosa (only the second observation in Morocco). It also highlights the therapeutic difficulties posed by this type of chromomycosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Arm; Chromoblastomycosis; Clarithromycin; Diabetes Complications; Diagnosis, Differential; Female; Hand Dermatoses; Humans; Itraconazole; Leishmaniasis, Cutaneous; Morocco; Naphthalenes; Phialophora; Terbinafine; Tuberculosis, Cutaneous

A global collection of Cladophialophora carrionii strains (n = 81) was tested against nine antifungal drugs. MIC90s of all strains were as follows in increasing order: itraconazole and posaconazole, 0.063 μg/ml; terbinafine, 0.125 μg/ml; isavuconazole and voriconazole, 0.25 μg/ml; caspofungin, 2 μg/ml; micafungin, 4 μg/ml; amphotericin B, 8 μg/ml; and fluconazole, 64 μg/ml.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Caspofungin; Chromoblastomycosis; Echinocandins; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Nitriles; Pyridines; Pyrimidines; Triazoles; Voriconazole

Subcutaneous dematiaceous fungal infections, which include chromoblastomycosis and phaeohyphomycosis, are a heterogeneous group of clinical entities that are caused by dematiaceous or pigmented fungi found in soil. These infections have a wide spectrum of clinical presentations that depend largely on the specific causative organism and on the integrity of the host's immune response. Treatment is challenging and involves a highly individualized plan that often combines both surgical and long-term medical treatment.

Topics: Acute Kidney Injury; Aged; Amphotericin B; Antifungal Agents; Chromoblastomycosis; Combined Modality Therapy; Costa Rica; Diagnosis, Differential; Humans; Immunocompromised Host; Immunosuppressive Agents; Itraconazole; Kidney Transplantation; Leg; Male; Phaeohyphomycosis; Pneumonia; Pyrimidines; Soil Microbiology; Triazoles; Voriconazole

The in vitro activities of eight antifungal drugs against clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested. The resulting MIC(90)s for all strains (n = 55) were as follows, in increasing order: posaconazole, 0.063 microg/ml; itraconazole, 0.125 microg/ml; isavuconazole, 0.25 microg/ml; voriconazole, 0.5 microg/ml; amphotericin B, 2 microg/ml; caspofungin, 2 microg/ml; anidulafungin, 2 microg/ml; and fluconazole, 32 microg/ml.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Ascomycota; Caspofungin; Chromoblastomycosis; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; In Vitro Techniques; Itraconazole; Lipopeptides; Microbial Sensitivity Tests; Nitriles; Pyridines; Pyrimidines; Triazoles; Voriconazole

We report a case of chromoblastomycosis which resembled sporotrichosis due to the presence of warty nodules and lymphatic distribution on the forearm in a 56-year-old male. Mycological and histopathological investigation of exudates and biopsy tissue samples revealed a granulomatous lesion with muriform cells, the hallmark of chromoblastomycosis. The infection showed only localized expansion with verrucous plaques suggesting a new clinical type of the disease. The causative agent was identified as Rhinocladiella aquaspersa. This case prompted a study of the clinical spectrum of R. aquaspersa, through which we identified a second case caused by this fungus in a 62-year-old Brazilian female. The case was unusual in that R. aquaspersa exhibited hyphae rather than muriform cells in tissue. Given the difficulties treating chromoblastomycosis and other infections caused by melanized fungi, we evaluated the in vitro activities of extended-spectrum triazoles, amphotericin B, and echinocandins against these clinical isolates of R. aquaspersa. Itraconazole (MIC; 0.063 mg/l) and posaconazole (MIC; 0.125 mg/l) had the highest in vitro activities, while voriconazole and isavuconazole had somewhat lower activities (MICs; 2 mg/l) against the isolates. Amphotericin B and anidulafungin each had an MIC of 1 mg/l, whereas the MIC of caspofungin was 8 mg/l.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Biopsy; Brazil; Chromoblastomycosis; Cytological Techniques; Echinocandins; Female; Forearm; Histocytochemistry; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Skin; Triazoles

The combined effects of terbinafine with itraconazole and amphotericin B against Cladophialophora carrionii, Phialophora verrucosa and Fonsecaea pedrosoi were evaluated in vitro by the checker-board method and expressed as a fractional inhibitory concentration (FIC) index. Synergy was observed with the combination of terbinafine and itraconazole against one isolate of C. carrionii and no antagonism was observed. When amphotericin B was combined with terbinafine or itraconazole, no synergy or antagonism was noted with all isolates included in this investigation.

Topics: Amphotericin B; Analysis of Variance; Antifungal Agents; Ascomycota; China; Chromoblastomycosis; Drug Interactions; Humans; In Vitro Techniques; Itraconazole; Microbial Sensitivity Tests; Naphthalenes; Phialophora; Terbinafine

Fonsecaea pedrosoi is the principal etiologic agent of chromoblastomycosis, a fungal disease whose pathogenic events are poorly understood. Current therapy for chromoblastomycosis is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the fact that endemic countries and regions are economically poor.. In the present work, we have investigated the effect of human immunodeficiency virus (HIV) peptidase inhibitors (PIs) on the F. pedrosoi conidial secreted peptidase, growth, ultrastructure and interaction with different mammalian cells. All the PIs impaired the acidic conidial-derived peptidase activity in a dose-dependent fashion, in which nelfinavir produced the best inhibitory effect. F. pedrosoi growth was also significantly reduced upon exposure to PIs, especially nelfinavir and saquinavir. PIs treatment caused profound changes in the conidial ultrastructure as shown by transmission electron microscopy, including invaginations in the cytoplasmic membrane, disorder and detachment of the cell wall, enlargement of fungi cytoplasmic vacuoles, and abnormal cell division. The synergistic action on growth ability between nelfinavir and amphotericin B, when both were used at sub-inhibitory concentrations, was also observed. PIs reduced the adhesion and endocytic indexes during the interaction between conidia and epithelial cells (CHO), fibroblasts or macrophages, in a cell type-dependent manner. Moreover, PIs interfered with the conidia into mycelia transformation when in contact with CHO and with the susceptibility killing by macrophage cells.. Overall, by providing the first evidence that HIV PIs directly affects F. pedrosoi development and virulence, these data add new insights on the wide-spectrum efficacy of HIV PIs, further arguing for the potential chemotherapeutic targets for aspartyl-type peptidase produced by this human pathogen.

Topics: Amphotericin B; Animals; Antifungal Agents; Cell Adhesion; Cell Line; Chromoblastomycosis; Drug Synergism; HIV Protease Inhibitors; Humans; Macrophages; Nelfinavir; Saquinavir; Spores, Fungal; Virulence

Chromoblastomycosis is a chronic infection caused by dematiaceous (dark-colored) fungi which affect the skin and subcutaneous tissues, and is characterized by a wide variety of clinical and dermatological features including papillomatous, verrucous and vegetating lesions. Although it has been described world-wide, most cases originate in tropical and sub-tropical areas. In general, present treatments of the disease are unsatisfactory as one of the most common etiologic agents, Fonsecaea pedrosoi is difficult to manage from a therapeutic point of view. We report a case of extensive chromoblastomycosis of 22 years duration caused by F. pedrosoi and review the clinical course, diagnosis and management of this disease.

Topics: Adult; Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; Drug Therapy, Combination; Humans; Itraconazole; Male; Mitosporic Fungi

Chromoblastomycosis is a cutaneous and subcutaneous mycotic disease caused by the dematiaceous (black) fungi. Five species of fungi are known generally to be the cause: Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, F. compacta and Rhinocladiella cerphilum. In infected tissue they can appear as pigmented sclerotic bodies, commonly called 'copper pennies', which are pathognomonic of chromoblastomycosis. The infection usually occurs through traumatic skin inoculation, with the majority of lesions occurring on the feet and legs of outdoor workers. We report a patient in whom the lesions had begun on the right breast, which is an unexposed area, without a history of trauma. A uniform, reliable treatment does not exist but our patient was mycologically cured with the use of amphotericin B and the subsequent combination of 5-flucytosine and itraconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Breast Diseases; Chromoblastomycosis; Dermatomycoses; Drug Therapy, Combination; Female; Flucytosine; Humans; Phialophora

Fourteen Fonsecaea pedrosoi isolates from six chromoblastomycosis patients were submitted to susceptibility testing. Some patients were undergoing treatment with itraconazole (ITZ) and/or cryosurgery with liquid nitrogen. The antifungal agents amphotericin B (AMB), ITZ, fluconazole (FCZ), ketoconazole (KCZ), 5-fluorocytosine (5-FC), and terbinafine (TBF) were tested. AMB and FCZ showed less activity for all isolates. The most active agents were KCZ and TBF. Sequentially isolates from four patients presented ITZ minimal inhibitory concentration (MIC) higher than the previous ones; for two of these patients, response to therapy with this agent was not observed. These results suggest development of microbiologic resistance to ITZ in four instances, two of them coinciding with lack of clinical response to this drug.

Topics: Amphotericin B; Antifungal Agents; Ascomycota; Chromoblastomycosis; Humans; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Mitosporic Fungi; Naphthalenes; Terbinafine

Despite the availability of modern antimycotics, which produce high cure rates in early infections, the therapy of advanced chromoblastomycosis is still unsatisfactory. An initial chromoblastomycosis caused by a hitherto unidentified species of the genus Phialophora was diagnosed in a 46-year-old teacher. The organism was isolated twice at an interval of 6 weeks from a partly psoriasiform, partly verrucous lesion on the 4th toe. The infection was apparently acquired 4 years ago during a holiday at Cape Verde. Treatment with itraconazole (Sempera). 200 mg/day, and amphotericin B (Ampho-Moronal) cream for 6 weeks initially resulted in rapid regression. However, 4 weeks after cessation of therapy, the Phialophora species was cultured again from skin scrapings. Complete healing was achieved after re-treatment with itraconazole for 20 weeks at the same dosage in combination with topical amorolfine and local hyperthermia. Until now, no relapse has occurred. The present case demonstrates that this rare disease, which mainly occurs as a traumatic mycosis in the rural population of tropical regions, must be included in the differential diagnosis of psoriasiform or verrucous skin lesions and also included in the list of diseases which may be acquired while on vacation in exotic locations.

Topics: Administration, Topical; Amphotericin B; Antifungal Agents; Chromoblastomycosis; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Foot Dermatoses; Humans; Itraconazole; Male; Middle Aged; Phialophora; Recurrence

Topics: Amphotericin B; Chromoblastomycosis; Humans; Male; Middle Aged; Mitosporic Fungi

Four patients with deep mycoses were treated with itraconazole. Two patients had chromoblastomycosis, one patient each had aspergillosis and Rhinofacial zygomycosis. These patients were either resistant to or showed poor response to Amphotericin B and/or ketoconazole. After the initial clinical and mycological evaluation, itraconazole was given in a daily dose of 200 mg orally. All patients responded to the drug very well. No adverse effects attributable to itraconazole were detected.

Topics: Adult; Amphotericin B; Antifungal Agents; Antitubercular Agents; Aspergillosis; Child; Chromoblastomycosis; Drug Resistance, Microbial; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Mucormycosis

A case of chromomycosis with an evolution of 25 years, in a caucasoid man, aged 57, living in Mozambique, is reported. Fonsecae pedrosoi, the most frequently responsible agent of chromomycosis in Mozambique's cases, was isolated. Prognosis seemed poor since good results from therapy were unexpected, considering the long course of disease, the extensive and fibrotic lesions, and the unsuccessful treatment with 5-fluorocytosine and ketoconazole. The patient was treated with associated amphotericin B-5-fluorocytosine, and topical heat. Clinical improvement and mycologic negative studies were obtained.

Topics: Amphotericin B; Chromoblastomycosis; Flucytosine; Humans; Ketoconazole; Male; Middle Aged; Mozambique

Topics: Amphotericin B; Chromoblastomycosis; Chronic Disease; Humans; Male; Middle Aged; Phialophora; Russia

Several cases of chromoblastomycosis have been observed, for 7 years, in the laboratory of Pathology, in the IMTSSA . Their various aspects are described. The diagnosis includes three stages: clinic, mycology and pathology. The most frequent clinical lesions have been observed on the legs. Often, they were like a malignant tumour (carcinoma). The fungal investigation, by direct research of fungi in the lesions, is carried out scarcely, because it is difficult. It should be completed by cultures, in order to isolate the pathogenic agent, but its identification is not possible, if it is not carried out by a laboratory of mycology. The most simple technique , adapted to tropical areas, is the pathological examination. It reveals several points of interest: by analyzing the cutaneous lesions (in order to eliminate a carcinoma)--observing the intensity of the inflammatory reaction--but, first of all, the discovery of the thick-walled dark cells. Two techniques are usual, for staining, but they could be improved by using other special techniques, in order to analyse more carefully the lesions.

Topics: Amphotericin B; Chromoblastomycosis; Flucytosine; Humans

The authors are confirming the efficacy of the combination of Anfotericina B y 5-fluorocitosine in the treatment of Cromoblastomicosis. The used program was as follows: 50 mg. of Anfotericine-B by intravenous injection every two days during 13 weeks (39 dosis). Simultaneously tablets of 500 mg. of 5-fluorocitesina, every 6 hours, oral, also daily during 13 weeks (194 gramos dosis total) were given. The two treated patients were under monthly control during 10 months and observing no relapse of the disease, with other words there exists already a clinical and histological cure (healing). In one case it was observed a change in the ble blood chemistry which spontaneously normalized when suspending the combined treatment for one week and did not repeat when starting a new treatment.

Topics: Administration, Oral; Aged; Amphotericin B; Chromoblastomycosis; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Infusions, Parenteral; Male

Topics: Amphotericin B; Chromoblastomycosis; Cytosine; Drug Resistance, Microbial; Drug Synergism; Flucytosine; Humans

Three different types of cutaneous chromomycosis, verrucous tumor type, eroded granuloma type and scaly erythematous plaque type, are reported. All these cases were successfully treated with intralesional injections of procaine-amphotericin B solution. This treatment for cutaneous chromomycosis seems to be favorable because of evident clinical efficiency without severe local or systemic side effects.

Topics: Administration, Topical; Amphotericin B; Chromoblastomycosis; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged

The authors discuss the problem of resistance of chromomycosis to 5-fluorocytosine (5-FC), observed in a previous study in 7 patients initially treated with the drug and subsequently treated with 5-FC associated with other medicaments. All the associations, including that with amphotericin B, failed to overcome resistance. Experiments in mice and "in vitro" show a synergism between 5-FC and amphotericin B against "C. albicans", "C. neoformans" and "Fonsecaeae pedrosoi" already confirmed in human subjects infected with the above mentioned fungi. Resistance to 5-FC seems to be irreversible, as shown in previous experiments. The mechanism of action of the drugs on the fungi is discussed, as well as the fact that amphothericin B prevents the development of resistance to 5-FC. Results obtained with the use of the above association in 5 cases of chromomycosis are presented; all the patients had old and well established lesions, and in three cases these lesions were large and disseminated, conditions probably associated with the development of resistance to 5-FC used alone. The drugs were given in small doses, inferior to those usually recommended. The good therapeutic results seem to confirm the synergism observed in laboratory trials. Four cases were discharged as cured and one abandoned treatment for personal reasons. The association seems to act more rapidly than 5-FC alone. Tolerance was excellent in all cases.

Topics: Adult; Aged; Amphotericin B; Capsules; Chromobacterium; Chromoblastomycosis; Cytosine; Drug Evaluation; Drug Therapy, Combination; Flucytosine; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Adult; Amphotericin B; Chromoblastomycosis; Ear Diseases; Ear, External; Humans; Male

Three cases of chromomycosis from Eastern Nigeria are described. The aetiological agent was identified as Phialophora pedrosoi. Amphotericin B cleared most of the lesions in one case while 5-fluorocytosine gave a complete cure in another case.

Topics: Adult; Amphotericin B; Chromoblastomycosis; Female; Flucytosine; Humans; Male; Middle Aged; Nigeria; Phialophora

The author presents a case of exogenous, retrocorneal, limbal infiltration due to chromomycosis, following cataractextraction. Since the etiology of this keratitis was not recognized at the beginning, steroids were applied causing an exacerbation of the keratitis with hypopyoniritis. A perforating, excentric keratoplasty was performed, yielding material for the histological diagnosis, and for the identification of the responsible agent. The cultural and morphological properties were typical of those of a dematiaceous fungus, a chromomycosis. In vitro studies demonstrated this fungus to be less sensitive to 5-fluorcytosin and clotrimazole, and to be less resistant to natamycin, mystatin and amphotericin-B, paving the road for an effective conservative therapy following surgery.

Topics: Amphotericin B; Chromoblastomycosis; Cornea; Female; Humans; Keratitis; Middle Aged

Clinical and laboratory features of 16 cases of keratitis that were caused by dematiaceous pigmented fungi are reported. Management, including the treatment of nine cases with Natamycin (Pimaricin), resulted in corneal healing in 14 cases, and therapeutic surgery in two cases.

Topics: Administration, Topical; Adolescent; Adult; Amphotericin B; Child; Chromoblastomycosis; Corneal Ulcer; Female; Gentamicins; Humans; Keratitis; Middle Aged; Mycoses; Natamycin; Visual Acuity

Topics: Actinomycosis; Amphotericin B; Blastomycosis; Candida albicans; Candidiasis, Cutaneous; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Griseofulvin; Histoplasmosis; Mucormycosis; Mycetoma; Sporotrichosis; Tinea Capitis; Tinea Pedis; Tinea Versicolor

Topics: Adolescent; Amphotericin B; Arachnoiditis; Chromoblastomycosis; Cisterna Magna; Humans; Male; Spinal Cord Diseases; Subarachnoid Space

Topics: Adolescent; Amphotericin B; Chromoblastomycosis; Cytosine; Fluorides; Humans; Jamaica; Male; Phialophora; United Kingdom

Topics: Amphotericin B; Chromoblastomycosis; Cytosine; Fluorine; Humans; Thiabendazole

Topics: Amphotericin B; Aortic Valve; Catheterization; Chromoblastomycosis; Embolism; Endocarditis; Female; Heart Valve Prosthesis; Humans; Middle Aged; Mitosporic Fungi; Mitral Valve; Prognosis

Topics: Amphotericin B; Anticonvulsants; Blood Sedimentation; Brain Abscess; Cerebral Cortex; Chromoblastomycosis; Electroencephalography; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Phialophora; Postoperative Complications; Radionuclide Imaging; Sulfonamides

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Chemical Phenomena; Chemistry; Chromoblastomycosis; Cryptococcosis; Cytosine; Fluorine; Fungi; Haplorhini; Humans; Injections, Subcutaneous; Mice; Rats

Topics: Adult; Agricultural Workers' Diseases; Amphotericin B; Antifungal Agents; Candida; Cheek; Chromoblastomycosis; Cytosine; Fluorine; Granuloma; Humans; Laryngeal Diseases; Male

Topics: Amphotericin B; Animals; Brain; Chromoblastomycosis; Kidney; Liver; Lung; Lymph Nodes; Mice; Omentum; Pancreas; Phialophora; Spleen; Stomach; Virulence

Topics: Amphotericin B; Chromoblastomycosis; Diagnosis, Differential; Fungi; Humans; Laryngeal Diseases; Male; Middle Aged; Nystatin

Topics: Adult; Amphotericin B; Chromoblastomycosis; Electrocoagulation; Female; Humans; Male; Methods; Middle Aged; Skin Transplantation

Topics: Adult; Amphotericin B; Brain Diseases; Chromoblastomycosis; Diagnosis, Differential; Female; Humans; Isoniazid; Liver; Lymph Nodes; Mitosporic Fungi; Multiple Sclerosis; Tuberculosis, Pulmonary

Topics: Amphotericin B; Chromoblastomycosis; Humans; Injections; Male; Middle Aged

Topics: Amphotericin B; Breast; Child; Chromoblastomycosis; Female; Humans; Indiana; Ointments; Phialophora; United States

Topics: Amphotericin B; Biopsy; Chromoblastomycosis; Humans; Injections, Intravenous; Male; Middle Aged; Nigeria

Topics: Amphotericin B; Animals; Bites and Stings; Chromoblastomycosis; Drug Therapy; Ergocalciferols; Humans; Iodides; Knee; Reptiles; Thigh; USSR; Zoonoses

Topics: Amphotericin B; Chromoblastomycosis; Epidemiology; Humans; Minor Surgical Procedures; Podophyllin; Podophyllum; Radiotherapy; Texas

Topics: Amphotericin B; Chromoblastomycosis; Electrocoagulation; Humans

Topics: Amphotericin B; Chromoblastomycosis; Ethnicity; Humans

Topics: Amphotericin B; Chromoblastomycosis; Humans

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Chromoblastomycosis; Fungicides, Industrial; Humans; Medical Records; Pharmaceutical Solutions; Solutions

Topics: Amphotericin B; Antifungal Agents; Chromoblastomycosis; Fungicides, Industrial; Humans; Pharmaceutical Solutions; Solutions

Topics: Amphotericin B; Antifungal Agents; Chromoblastomycosis; Humans; Injections