RESUMO
BACKGROUND: Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The simultaneous use of PTX and antifungal therapy (itraconazole) has previously been evaluated in an experimental model of pulmonary paracoccidioidomycosis (PCM), a systemic fungal disease caused by the fungus Paracoccidioides brasiliensis (Pb) and characterized by chronic inflammation and lung fibrosis that appears even after a successful course of antifungal therapy. The results revealed prompt and statistically significant reductions in inflammation and fibrosis when compared to itraconazole alone. However, the effect of monotherapy with PTX on the host response to PCM has not been well-documented. Our aim was to determine the effect of PTX on the course of pulmonary lesions and on the local immune response. RESULTS: At the middle and end of treatment, the Pb-infected-PTX-treated mice exhibited significant reductions in lung density compared to the Pb-infected-non-treated mice as assessed by the quantification of Hounsfield units on high-resolution computed tomography (HRCT) (p <0.05 by Kruskal-Wallis test); additionally, at the end of therapy, the lung areas involved in the inflammatory reactions were only 3 vs. 22 %, respectively, by histomorphometry (p <0.05 by Mann-Whitney test), and this reduction was associated with a lower fungal burden and limited collagen increment in the pulmonary lesions. PTX treatment restored the levels of IFN-γ, MIP-1ß, and IL-3 that had been down-regulated by Pb infection. Additionally, IL-12p70, IL-10, IL-13, and eotaxin were significantly increased, whereas Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) levels were decreased in the lungs of the Pb-infected-PTX-treated mice compared to the non-treated group. CONCLUSIONS/SIGNIFICANCE: This study showed that PTX therapy administered at an "early" stage of granulomatous inflammation controlled the progress of the PCM by diminishing the pulmonary inflammation and the fungal burden and avoiding the appearance of collagen deposits in the pulmonary lesions.
RESUMO
BACKGROUND: Disseminated candidiasis is caused by different Candida species and mainly affects immunocompromised patients and those hospitalized in intensive care units (ICU). OBJECTIVE: Our aim was to determine the frequency and susceptibility of Candida spp. isolates to fluconazole and voriconazole, obtained from patients hospitalized in ICU in the city of Medellin during the years 2001-2007. METHODS: The agar diffusion technique based on the protocols recommended by the CLSI from the United States (M44A) was used. The Chi² test and the Kruskal Wallis statistical methods were used to compare changes in the frequency of Candida spp. isolates and their susceptibility to azoles by year of isolation. RESULTS: A total of 337 isolates were analyzed, 147 (43.6%) of which corresponded to Candida albicans, followed by 79 (23.4%) Candida tropicalis, 47 (13.9%) Candida parapsilosis, 32 (9.5%) Candida glabrata, 12 (3.6%) Candida guilliermondii and 11 (3.3%) Candida krusei. The remaining isolates (2.7%) were distributed among other species (Candida famata, Candida lusitaniae, Candida lipolytica, Candida pelliculosa and Candida spp.) Most of these isolates (78.3%) were susceptible; 11.9% were dose-dependent susceptible (DDS) and 9.8% resistant to fluconazole. For voriconazole, we observed that 94.1% of the isolates were susceptible, 2.4% DDS and 3.6% resistant. CONCLUSIONS: These data indicate a notable change in the species frequency, as well as a new susceptibility patterns that requires the precise identification of the causative organism and susceptibility testing in order to determine the characteristics of the isolates circulating in ICUs and then to treat them appropriately.
