Simultaneous cutaneous infection due to Paecilomyces lilacinus and Alternaria in a heart transplant patient.

Paecilomyces lilacinus is an emerging pathogen in immunocompromised patients. We report here a case of cutaneous hyphomycosis in a 63-year-old heart transplant recipient caused by the simultaneous presence of 2 molds: Paecilomyces lilacinus and Alternaria alternata. The infection was successfully treated with local voriconazole followed by oral terbinafine.

[Quality controls in medical mycology]. / Les contrôles de qualité en mycologie médicale.

The Quality Management System in medical mycology refers to the systematic monitoring with internal and external quality controls: it needs to be organized in the laboratory. ISO 15189 standard is not precise in how to demonstrate the correctness of tests, in terms of frequency and requirements for quality controls QC. That's why the COFRAC, the French Accreditation Committee has published guides to which we should refer. The laboratory has to apply internal Quality Control Programs. They consist of various tests to check the reagents including the culture media. Reference strains have to be provided and preparations of homemade reagents are needed, because few are commercialized. Maintaining the competence of the technical staff through identification of unknown strains is also required. In the fungal serology field, home made antibodies with pooled sera or antigen controls are needed. This monitoring has to follow the recommandations from the Cofrac technical guide LAB GTA 06. For quantitative analysis, the Levey-Jennings chart is a graph with quality control data plotted on to give a visual indication. Some external QC references, besides the national quality control AFSSAPS, are available. Data evaluation, corrective actions in case of out of range results and preventive actions have to be determined in the Quality System documents and presented in the annual management review.

[Fungal keratitis caused by Scedosporium apiospermum]. / Kératite fongique à Scedosporium apiospermum.

INTRODUCTION: We report a case of posttraumatic keratomycosis caused by Scedosporium apiospermum that was treated with oral and topical voriconazole and penetrating keratoplasty. CASE REPORT: A patient was admitted to the hospital with a corneal abscess of his right eye due to trauma while gardening. No improvement was noted with topical fortified antibiotics (vancomycin, gentamicin, and cefazolin) and antimycotic (amphotericin B 1%) and oral itraconazole (200 mg/day). Fungal cultures of corneal scrapings revealed growth of Scedosporium apiospermum, a strain for which the main antifungals showed high minimal inhibitory concentrations (MICs), whereas the MIC of voriconazole was 0.125 microg/mL. Despite some improvement with topical 1% voriconazole and oral voriconazole (200 mg/day) treatment, a therapeutic penetrating keratoplasty was performed because of the high risk of corneal perforation. The graft remained clear without fungal recurrence with topical 2% cyclosporine A, dexamethasone, and voriconazole treatment. CONCLUSION: Scedosporium apiospermum is an uncommon cause of mycotic keratitis in humans. Prognosis is generally poor because of delayed diagnosis and resistance to conventional antifungals. Voriconazole is a triazole broad-spectrum antifungal agent. In conjunction with its oral administration, topical application of voriconazole extends the current armamentarium of antifungal agents for keratomycosis.

Aspergillus fumigatus-related spondylodiscitis in a heart transplant patient successfully treated with voriconazole.

Organ transplant patients, such as heart transplant (HT) recipients, are prone to infections, among which are yeast infections. Of these, aspergillosis is usually associated with pneumopathy or facial sinusitis, and Aspergillus fumigatus is rarely responsible for osteomyelitis or spondylodiscitis. Herein we have reported a case of an 18-year-old male HT patient presenting with subacute lumbar spondylodiscitis at 6 months posttransplantation and 3 months after antirejection therapy with antithymocyte globulins. A percutaneous needle biopsy of the intervertebral disc yielded Aspergillus fumigatus. The patient had no evidence of lung aspergillosis, but did have maxillary sinusitis. He was successfully treated with voriconazole.

Scedosporium apiospermum mycetoma with bone involvement successfully treated with voriconazole.

Treatment of Scedosporium apiospermum mycetoma usually requires limb amputation. A 49-year-old woman, from Ivory Coast, was diagnosed with Madura foot in 1995. She failed to respond to several treatments including itraconazole, fluconazole and co-trimoxazole, and refused limb amputation. In December 2002 she was admitted to hospital in France with a painful, swollen right leg and foot. She had no fever and C-reactive protein was 120 mg/l. Magnetic resonance imaging (MRI) confirmed the destruction of tarsus bones with a tibia extension. Voriconazole (400 mg/day) treatment was initiated in March 2003; a significant clinical improvement was observed within 4 months as confirmed by C-reactive protein (16 mg/l) and MRI. Voriconazole was maintained for 18 months with good tolerance. Cholestasis appeared after the first month and remained stable. In October 2004 voriconazole was discontinued due to side effects on the liver (alanine aminotransferase 17 times the normal level); MRI showed impressive regression of bone lesions. As of July 2005, the patient remains clinically well. Voriconazole appears to be a promising drug for the treatment of S. apiospermum mycetomas.

Improved oral hygiene and Candida species colonization level in geriatric patients.

OBJECTIVES: This work consists in improving oral hygiene (OH) for elderly dependent people in long-term hospital care, in order to decrease the degree of colonization and the associated risk of developing oral candidiasis. As this population frequently suffers from such colonization and because it is difficult to install and practice OH care, a study protocol was designed at the request of geriatricians. The objective of the present study was to set up a programme of OH, applied by the care staff, and to monitor oral colonization of by Candida spp. BASIC RESEARCH DESIGN: We compared the levels of hygiene and Candida spp. colonization for a group of 110 long-term patients in geriatric departments at T1, when clinical data were collected and oral mycological samples taken before the OH protocol was applied, and at T2, during the postprotocol phase after 3 months of application, when the clinical data and sample collection were repeated. RESULTS: During these 3 months 11 patients died. These patients were excluded from the results, which are presented for matched series of the 99 patients still present at T2. Statistical analysis comparing the clinical and biological parameters at T1 and T2 established that there had been an improvement in OH: the 'adequate' level was reached for 72.4% of patients at T2 compared with 41.8% at T1 (P < 0.001) and the 'very inadequate' level was observed for 9.2% at T2 compared with 27.9% at T1 (P < 0.01). A reduction was observed in the number of patients showing the highest degree of C. albicans and C. glabrata colonization (> 50 colony forming units) from 41.9% at T1 to 24.9% at T2 (P < 0.05) and from 56.4% at T1 to 13.0% at T2 (P < 0.05) respectively. The number of patients with candidiasis fell significantly from 43.2% at T1 to 10.2% at T2. CONCLUSIONS: The OH protocol led to an overall decrease in Candida spp. colonization, a significant reduction in the number of candidiasis and an improvement in the level of oral and denture hygiene but vigilance is still necessary concerning OH care and the initial training of staff in specific care of the mouth.

In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.

Value of investigation in the diagnosis of allergic fungal rhinosinusitis: results of a prospective study.

The authors report a prospective study in which the aim was to analyse the usefulness of different criteria in optimizing the diagnosis of allergic fungal rhinosinusitis. From 1995 to 1998, 165 patients were operated on for chronic rhinosinusitis. Investigations used in this study for the diagnosis of allergic Aspergillus rhinosinusitis consisted of an analysis of clinical, radiological, immuno-allergic criteria. Fourteen patients presented with allergic Aspergillus rhinosinusitis. One hundred and fifty-one patients did not present any of the necessary criteria for the diagnosis of allergic Aspergillus rhinosinusitis. The results show that the characteristic macroscopic appearance, the maxillary sinus localization, and the presence of positive specific IgE to Aspergillus fumigatus are arguments that reinforce the diagnostic certitude of allergic fungal sinusitis. No specific clinical or radiological criteria orients a diagnosis of chronic rhinosinusitis toward that of allergic fungal rhinosinusitis. The other immuno-allergic tests do not contribute to the diagnosis of allergic fungal rhinosinusitis. pathological, mycological, and

[A rare cause of asthma exacerbation: systemic anguilluliasis]. / Une cause rare de décompensation de l'asthme: l'anguillulose systémique.

Strongyloides is an helminthic infection that may induce bronchospasm during systemic migration of larvae. We report a case of a 60 years old man originating from Caribbean who had corti-codependent asthma since 30 years. He was hospitalized for severe exacerbation that worsen when steroid dosage was increase. Sputum examination revealed the presence in great number of Larvae of Strongyloides stercoralis. A good clinical evolution was achieved after specific anti-helminthic treatment. Later on, it was even possible to stop completely steroid treatment. This clinical case demonstrates the interest to look for Strongyloides superinfection in asthmatic patients that worsen when receiving increasing dose of steroids. This is particularly important for patients who have resided, even many years earlier, in areas where intestinal helminthic infection are endemic.

Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS.

A patient with AIDS and chronic diarrhea caused by Enterocytozoon bieneusi was successfully treated with nitazoxanide, producing a complete clinical and parasitological response, while off of antiviral therapy. This suggests that nitazoxanide may be effective in treating microsporidiosis caused by E. bieneusi, a disease for which there is no established treatment.

[Does allergic fungal sinusitis exist? Preliminary results of a prospective study]. / La sinusite aspergillaire allergique existe-t-elle? Résultats préliminaires d'une étude prospective.

Allergic aspergillar sinusitis is a very controversial clinical feature. We present results of a prospective study aimed at evaluating the reality of allergic aspergillar sinusitis in a nosologic and clinical point of vue. During a 5 months period, 31 patients underwent surgery: 21 sino-nasal polyposis, 5 chronic sinusitis without polyposis, 5 chronic sinusitis with radiologic images evocative of mycosis. The study was carried out using clinical criteria (per-operative discovery of glue-like, thickened and viscous aspect of the secretions), pathologic criteria (the presence of elements consitutive of allergic mucin), mycological criteria (direct examination and culture), and immunoallergic criteria (specific IgE for Aspergillus fumigatus, serology for Aspergillus fumigatus and Aspergillus flavus (IgM, IgG), skin tests for Aspergillus fumigatus). In three cases we suspect an allergic aspergillar sinusitis (one patient presenting a bilateral chronic sinusitis and two patients presenting a sinonasal polyposis). In two patients presenting a sinonasal polyposis, a allergic fungal sinusitis was suspected, fungal identification was not possible.

[Allergic bronchopulmonary aspergillosis in children]. / Aspergillose bronchopulmonaire allergique chez l'enfant.

Allergic bronchopulmonary aspergillosis (ABPA) associates the development of aspergillus in bronchus and a predominant immediate hypersensitivity for aspergillus antigens. It complicates an old and severe allergic asthma or cystic fibrosis. Its prevalence is not well known. In children, ABPA prevalence is rare, except in cystic fibrosis where 0.6% to 11% of patients can be affected by the disease. Acute exacerbation of the disease favours the development of bronchiectasis and fibrosis. The diagnosis is suggested by an unexplained aggravation of asthma or, in cystic fibrosis, by wheezing, an unsuccessful antibiotherapy, and a recent modification of the chest X-ray. The diagnosis is based upon the presence of seven major criteria or six major criteria and one minor. The follow-up of biological parameters is important for early diagnosis of exacerbations. Some parameters are very sensitive, ie, precipitins and total serum IgE. Systemic corticotherapy is the usual treatment of exacerbation. The association with inhaled corticotherapy could reduce the duration of systemic treatment. The use of Itraconazole is logical, mainly in cystic fibrosis.

New in vitro assay based on glucose consumption for determining intraconazole and amphotericin B activities against Aspergillus fumigatus.

We developed a new in vitro method of evaluating antifungal molecules. Fungal growth was determined by measuring glucose consumption, the only carbon source in a synthetic medium. First, the growth of 12 Aspergillus fumigatus strains was studied. Glucose consumption was an excellent indicator of fungal growth. Second, the partial inhibition of growth was calculated in terms of the 90% or 50% inhibitory concentration for the 12 strains after treatment with itraconazole and amphotericin B. With a 3-day incubation time, the calculated 90% and 50% inhibitory concentrations agreed with those obtained by a macromethod and with those reported in previous publications. In each case the high degrees of efficacy of itraconazole and amphotericin B against A. fumigatus were confirmed. Partial inhibition induced by low concentrations of antifungal agents was quantifiable by this new method.

Enhancing resistance and modulation of humoral immune response to experimental Candida albicans infection by patulin.

Mice receiving patulin (10 mg/kg) from 1 to 4 days showed enhancing resistance to intraperitoneal challenge with 10(8) viable Candida albicans at day 2. Resistance to C. albicans infection (10(6) blastospores) appeared to be unchanged after cyclophosphamide oral administration (60 mg/kg). Immunoglobulins levels (IgA, IgM, IgG) are marked depressed (10 to 75%) in mice infected and/or treated by patulin and cyclophosphamide. The results show that an increase of neutrophil count may be among the factor underlying the late increase in resistance to C. albicans after administration of patulin.

Experimental study of the intra-ocular penetration of ketoconazole in rabbits.

We studied 11 healthy rabbits and 15 rabbits with experimentally induced Candida endophthalmitis. Using a microbiological procedure, ketoconazole levels were determined 1, 2, 4, 8 and 24 h after its oral administration. Ketoconazole penetration was average in the aqueous humour, significant in tears and poor in the vitreous. Vitreous penetration was not detectable in healthy rabbits or in rabbits with chorioretinits exhibiting little or no vitreous reaction. Such penetration was only significant in rabbits exhibiting massive vitreous exudation; however, in such rabbits, penetration was not always observed (only in 2 out of 6 animals). Given these results, the treatment of Candida endophthalmitis in humans using ketoconazole would appear to be of questionable value.