Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole

BACKGROUND: The current recommended therapy for diffuse coccidioidal pneumonia involves initial treatment with amphotericin B deoxycholate or high-dose fluconazole, followed by an azole after clinical improvement. Amphotericin B is more frequently used as initial therapy if the patient's deterioration is rapid. CASE PRESENTATION: A 31-year-old Korean male with coccidioidomycosis presented to the hospital with miliary infiltrates on chest X-ray (CXR) and skin rash on the face and trunk. Initially, the patient did not respond to amphotericin B deoxycholate therapy. However, following caspofungin and fluconazole combination therapy, the patient showed favourable radiological, serological, and clinical response. CONCLUSION: This appears to be the first case of diffuse coccidioidal pneumonia with skin involvement in an immunocompetent patient who was treated successfully with caspofungin and fluconazole. Combination therapy with caspofungin and fluconazole may, therefore, be an alternative treatment for diffuse coccidioidal pneumonia that does not respond to amphotericin B deoxycholate therapy

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-Year Analysis of Susceptibilities of Candida Species to Fluconazole and Voriconazole as Determined by CLSI Standardized Disk Diffusion ▿

Fluconazole in vitro susceptibility test results for 256,882 isolates of Candida spp. were collected from 142 sites in 41 countries from June 1997 to December 2007. Data were collected for 197,619 isolates tested with voriconazole from 2001 to 2007. A total of 31 different species of Candida were isolated. Increased rates of isolation of the common non-albicans species C. glabrata (10.2% to 11.7%), C. tropicalis (5.4% to 8.0%), and C. parapsilosis (4.8% to 5.6%) were noted when the time periods 1997 to 2000 and 2005 to 2007 were compared. Investigators tested clinical isolates of Candida spp. by the CLSI M44-A disk diffusion method. Overall, 90.2% of Candida isolates tested were susceptible (S) to fluconazole; however, 13 of 31 species identified exhibited decreased susceptibility (<75% S), similar to that seen with the resistant (R) species C. glabrata and C. krusei. Among 197,619 isolates of Candida spp. tested against voriconazole, 95.0% were S and 3% were R. About 30% of fluconazole-R isolates of C. albicans, C. glabrata, C. tropicalis, C. rugosa, C. lipolytica, C. pelliculosa, C. apicola, C. haemulonii, C. humicola, C. lambica, and C. ciferrii remained S to voriconazole. An increase in fluconazole resistance over time was seen with C. parapsilosis, C. guilliermondii, C. lusitaniae, C. sake, and C. pelliculosa. Among the emerging fluconazole-R species were C. guilliermondii (11.4% R), C. inconspicua (53.2% R), C. rugosa (41.8% R), and C. norvegensis (40.7% R). The rates of isolation of C. rugosa, C. inconspicua, and C. norvegensis increased by 5- to 10-fold over the 10.5-year study period. C. guilliermondii and C. rugosa were most prominent in Latin America, whereas C. inconspicua and C. norvegensis were most common in Eastern European countries. This survey identifies several less-common species of Candida with decreased susceptibility to azoles. These organisms may pose a future threat to optimal antifungal therapy and underscore the importance of prompt and accurate species identification and antifungal susceptibility testing

Détection of mucorales DNA in serum: retrospective analysis of 44 mucormycoses collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF)

International audienc

Heterogeneity in cellular and humoral immune responses against Toxoplasma gondii antigen in humans

Protection against Toxoplasma gondii in infected patients is mainly attributed to cellular immunity. We here attempt to improve the characterization of the proteins that induce cellular immunity in naturally infected patients. Cellular immunity was evaluated by flow cytometry after 7 days of blood culture from 31 chronically T. gondii infected and 8 noninfected pregnant women, in the presence of soluble T. gondii antigen (ST-Ag) or fractionated proteins from ST-Ag, separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Blood cultures from infected patients with ST-Ag induced 39·5 ± 12·7% of activated (CD25+) CD4+ T cells using flow cytometry. This contrasts with the absence of activated CD4+ T cells after either culture with PBS or in blood cultures from noninfected women. The protein fraction between 21 and 41·9 kD induced the highest response (14·7 ± 10·0%). Blood samples from 20 infected and 5 uninfected women were cultured in presence of 12 protein subfractions of 2–208 kD. The highest frequencies of response among infected patients were seen with fractions (Fr) 26–31·9 kD (C.I. 85–100%) and Fr 32–36·9 kD (C.I. 77–100%). Although we note a good concordance between cellular and humoral response, Western blot analysis of ST-Ag does not completely predict the panel of proteins recognized by cellular immunity. Two-dimensional separation of the ST-Ag revealed more than 200 protein spots in these fractions. However, only two proteins in the 20–40 kD range induced a significant humoral response. Further studies are necessary to determine which proteins in the Fr 26–31·9 kD and 32–36·9 kD are superior immunogens for cellular responses