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.

Fulminant invasive pulmonary aspergillosis in immunocompetent patients--a two-case report.

Two cases of invasive aspergillosis (IA) in immunocompetent patients with a fulminant fatal outcome are reported. Both patients were elderly and had a history of chronic lung disease treated with prolonged inhaled corticosteroids and a short course of systemic corticosteroids. They presented with dyspnea and fever, their respiratory function deteriorated rapidly, and they died 7 days after admission. Aspergillus fumigatus was cultured from respiratory samples. IA was confirmed in one case by necropsy that showed diffuse bilateral necrotizing pneumonitis and myocarditis. In the other case, IA diagnosis was established by thoracic CT scan plus detection of Aspergillus antigen in two blood samples. These two cases demonstrate that short-term corticosteroid therapy in immunocompetent patients with underlying chronic lung conditions is a risk factor for IA, and that its evolution can be fulminant.

Invasive infections due to Trichoderma species: report of 2 cases, findings of in vitro susceptibility testing, and review of the literature.

Trichoderma species are filamentous fungi that were previously considered to be culture contaminants. We report 2 well-documented cases of invasive Trichoderma infections, and we comprehensively review the literature on this topic. Trichoderma species are mainly responsible for continuous ambulatory peritoneal dialysis-associated peritonitis (7 cases) and invasive infections in immunocompromised patients (9 cases) with a hematologic malignancy or solid-organ transplant. Definitive diagnosis is difficult to achieve because of the lack of specific diagnosis tools. Species identification can benefit from a molecular approach. Trichoderma longibrachiatum is the most common species involved in these infections. Regardless of the type of infection, the prognosis was poor, with 8 deaths among 18 cases. This may be partially because of the resistance of these organisms to the majority of available antifungal agents, including amphotericin B. Trichoderma species now should be added to the growing list of emerging filamentous fungal pathogens.

Trichinella murrelli: pathological features in human muscles at different delays after infection.

The authors describe the pathological aspects of muscles of three patients infected with Trichinella murrelli. Biopsies were carried out at various intervals. Six weeks after infection, the muscular larvae were not encapsulated whereas encapsulation was seen 10 weeks after infection. Six years after infection, the larvae were still alive in a nurse cell surrounded by a very thick capsule. Fourteen years after infection, cuticular larvae remnants were seen in degenerating nurse cells. The late encapsulation of Trichinella murrelli in human muscles could explain some clinical differences noticed during the outbreak during which these three patients were infected.

Neosynthesized IgG detected by Western blotting in Toxoplasma-seropositive heart or lung transplant recipients.

Toxoplasmosis is a life-threatening disease in heart- or lung transplant recipients that can result either from the reactivation of a latent infection or from an organ-transmitted infection. The diagnosis of acute toxoplasmosis is easy in cases of seroconversion following a mismatch. However, when the recipient is Toxoplasma-seropositive before transplantation, usual serological techniques do not allow the differentiation between endogenous and organ-related reinfection. The aim of this study was to determine whether western blotting could contribute to this differentiation. Sequential sera from two heart- and one liver- and lung transplant patients whose anti-Toxoplasma antibody titers strongly increased after transplantation, were analyzed by western blotting. Neosynthesized IgG were observed on blots incubated with the sera from two patients who had received transplants from Toxoplasma-seropositive donors, whereas no neosynthesized IgG was detected on blots from the patient who had received a transplant from a Toxoplasma-seronegative donor. Our results suggest that the detection of neosynthesized IgG in the recipient may be related to the recognition of a new parasite strain possibly brought by the transplant from a Toxoplasma-seropositive donor.

Identification of Fusarium species involved in human infections by 28S rRNA gene sequencing.

Fusarium spp. have emerged as major opportunistic fungal agents. Since new antifungal agents exhibit variable activity against Fusarium isolates depending on the species, rapid identification at the species level is required. Conventional culture methods are difficult, fastidious, and sometimes inconclusive. In this work, we sequenced a 440-bp fragment encoding the 28S rRNA from 33 Fusarium isolates belonging to six Fusarium species associated with human infections. The data were then analyzed by the neighbor-joining method. By using distance matrix analysis and constructing the phylogram, we could easily distinguish the different species for all but one isolate. The method also allowed differentiation between the closely related genera Acremonium and Cylindrocarpon. In contrast to the case with conventional methods, the results could be obtained within 48 h from a 3-day culture and are independent of mycologist experience, making this method rapid and reliable for identification of Fusarium species isolated from patients.

Disseminated Fusarium solani infection with endocarditis in a lung transplant recipient.

Eleven days after double lung transplantation for cystic fibrosis, an 18-year-old patient developed a disseminated Fusarium solani infection with tricuspid valve endocarditis. This infection occurred under fluconazole and immunosuppressive therapy with cyclosporin, prednisone and azathioprine, with a normal leucocyte count. Liposomal amphotericin B allowed blood culture negativation. The patient died from a bacterial septic shock.

Evaluation of a rapid enzyme immunoassay for diagnosis of hepatic amoebiasis.

We compared the capability of rapid enzyme immunoassay (EIA) to detect antiamoebic antibodies during hepatic amoebiasis with those of indirect hemagglutination and latex agglutination. EIA is simple to perform and rapid (20 min) and does not require any special equipment (optical reading is sufficient). EIA of 143 sera (including 43 from patients with proven hepatic amoebic abscess, 33 from patients with other hepatic disorders and/or parasitic infections, and 67 from healthy individuals) yielded a specificity, a sensitivity, and positive and negative predictive values of 100, 93, 100, and 97.1, respectively. This test could thus be considered another valuable tool for the diagnosis of hepatic amoebiasis.

Invasive Fusarium infections: a retrospective survey of 31 cases. The French 'Groupe d'Etudes des Mycoses Opportunistes' GEMO.

A retrospective study was conducted in France to investigate Fusarium infections which are now recognized as emerging opportunistic infections. The clinical and mycological findings for 31 cases diagnosed between 1984 and 1993 by members of the French Groupe d'Etudes des Mycoses Opportunistes were analysed. All suffered from haematological disease, most often acute leucaemia (n = 19). Twenty-two had received cytostatic chemotherapy and ten had undergone bone marrow transplantation. Prolonged aplasia and pancytopenia were present in 18 and 11 patients, respectively. Skin (61%) and blood (42%) were the sites most frequently involved. Fusarium solani (n = 7), Fusarium oxysporum (n = 7), Fusarium verticilloides (n = 7) were the species most frequently isolated. Nine antifungal treatments were used, associated with colony-stimulating factors in five cases. None was unambiguously superior to all the others. The overall mortality was 51.6% with a specific mortality > or = 25.8%. The disseminated form of the infection was associated with poor prognosis (P < 0.02) whereas improving granulocyte count improved prognosis (P < 0.001). More aggressive cytostatic regimens used for patients with haematological malignancies have favoured the emergence of Fusarium infections. As prognosis is closely correlated with neutrophil recovery, the promising results obtained with the use of colony-stimulating factors should be further evaluated.

[Pneumocystis carinii infection disclosing untreated systemic lupus erythematosus]. / Infection à Pneumocystis carinii révélatrice d'un lupus érythémateux disséminé non traité.

Pneumocystis carinii pneumonia (PCP) is a well known opportunistic infection in Systemic Lupus Erythematosus (SLE) patients with lymphopenia and treated with corticosteroid or cytotoxics agents. We report a new case of PCP in an untreated SLE with severe lymphopenia. We discuss the origin of lymphopenia in SLE, lymphopenia as a risk factor of Pneumocystis carinii infection, and safety precautions to take.

[Aspergillosis and renal, heart and lung transplantation]. / Aspergillose et transplantation rénale, cardiaque et pulmonaire.

The increase of organ transplantations during the last decades conjointly with the prescription of heavy immunosuppressive drugs, has led to an increased incidence of new invasive aspergillosis (IA). This study is a report of the Broussais Hospital experience from 1968 to 1993 on kidney, heart and heart and lungs transplantations. It concerns 21 IA cases. Incidence was 0.5% for kidney, 4.5% for heart and 18% for heart and lungs transplantations. The most important risk factors were the increase of immunosuppressive therapy (66% of the cases), neutropenia (19%), and renovation of the hospital wards (36%). Lung was the most frequent site of infection (95% of the cases), clinical symptoms were no significant. Diagnosis procedures were realised on biopsy (23%) and on bronchoalveolar lavage (66%). Usual amphotericin B treatment was disappointing: mortality rate of 77%, the liposomal preparation of the drug seemed to be more efficient: mortality rate of 50%. Itraconazole appeared to be used in succession with a careful adaptation of posology. Prophylactic amphotericin B in a local way (sprays and aerosols) led to a good efficiency jointly with the patient isolation during constructions in the hospital area.

[In vitro pharmacological study of fluconazole. Evaluation of an antifungal assay]. / Contribution à l'étude pharmacologique in vitro du fluconazole. Mise au point d'un antifongigramme.

Fluconazole is a new antifungal drug which is now very often used for the treatment of yeasts infections: mucocutaneous candidosis, systemic candidosis and cryptococcosis. Some resistance seems to occur in clinical practice. It turns out now that it must be necessary to test the drug susceptibility in vitro of the yeast strains isolated from patients. Unfortunately, a current laboratory technique to test this agent doesn't exist. In this work a useful method for Minimal inhibitory concentration (MIC) evaluation in a commercial available broth medium, and a technique for testing fluconazole disks on an agar medium are studied. 150 strains of different yeasts species are tested. A regression curve is performed to correlate the two methods.

[Study of specific immunoglobulins (total, IgG, IgM, IgA, IgE) in indirect immunofluorescence and ELISA in 40 patients with trichinosis followed over a 9-month period]. / Etude des immunoglobulines spécifiques (totales, IgG, IgM, IgA, IgE) en immunofluorescence indirecte et en ELISA chez quarante malades trichinés suivis pendant neuf mois.

The evolution of the classes of specific immunoglobulins (IgG, IgM, IgA, IgE) of 40 cases of human trichinosis was followed over a nine month period by means of an indirect immunofluorescence test (IF) and ELISA. Specific IgG and IgM appear between 4 and 6 weeks after infection and were still demonstrable after 9 months (respectively in 87.5% and 38.5% of the patients with IF, in 85% and 87.5% with ELISA). Specific IgA were mainly seen on the 2nd month and specific IgE were detected in 37.5% of the patients on the 4th month. In this outbreak, specific antibodies seem to appear later than in a second outbreak observed a few weeks later.

[Therapeutic trials of a new anti-helminthic in Colombian Amazonia: flubendazole]. / Essai thérapeutique d'un nouvel anti-helminthique en amazonie colombienne: le flubendazole.

After a coprologic survey made at Araracuara, a village in colombian Amazonia showing high prevalences of nematodosis, 83 villages (including 55 children below twelve) were given Flubendazole during three consecutive days. The total dose was 600 mg. for children below 12, and 900 mg. for adults. The product efficiency was 88% for Trichuris, 82% for Hookworm, 77% for Ascaris and 43% for Strongyloïdes. The tolerance was excellent in all cases, in spite of heavy parasital infection. The Flubendazole's effect seems to be particularly interesting by its polyvalency.

[Presence of Angiostrongylus cantonensis in the Réunion Island. Isolation of the strain]. / Existence d'Angiostrongylus cantonensis a la Réunion Isolement de la souche

The detection of some cases of eosinophilic meningitis suggest that Angiostrongylus cantonensis is present in Reunion Island. Larvae of this nematode have been isolated after dissection of Achatina fulica and have been used to infest laboratory rats. 30 days later, the dissection of these animals shows the presence of young worms in the brain and in the pulmonary arteries. 45 days later, first-stage larvae are recovered from the feces of animals. Now, the strain is maintained in Biomphalaria glabrata and in the rat.