Despite mixed findings, increasing evidence suggests that people with first-episode psychosis (FEP) show increased pro-inflammatory and pro-oxidative status. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to conduct a systematic literature search of cross-sectional studies comparing in vivo inflammatory and oxidative blood markers between FEP patients and healthy controls. We analyzed 61 independent samples from 59 publications, including 3002 patients with FEP (ie, patients with FEP, early psychosis, first-episode schizophrenia or early schizophrenia) and 2806 controls. After controlling for multiple comparisons, our meta-analysis showed that total antioxidant status and docosahexaenoic acid levels were significantly lower in FEP patients than in controls, whereas levels of homocysteine, interleukin-6 and tumor necrosis factor alpha were significantly higher in FEP patients than in controls. This suggests that FEP patients had reduced antioxidant status and a pro-inflammatory imbalance, and that these biological processes may be targets for managing FEP.

. All Candida isolates were from patients with candidemia. For isavuconazole, these techniques were also compared with the Etest. Isavuconazole and voriconazole had MICs at which 50% and 90% of isolates were inhibited (MIC 50 and MIC 90 ), respectively, of 1 and 1 g/ml and 0.5 and 1 g/ml against Aspergillus spp. and of 0.015 and 0.03 g/ml and 0.25 and 0.125 g/ml against Candida spp. (including fluconazole-resistant strains). The MIC 50 partial and complete inhibition end points of isavuconazole and voriconazole against the non-Aspergillus molds were as follows: 1 and 2 g/ml and 16 and >16 g/ml against Zygomycetes; 1 and 4 g/ml and 0.25 and 0.5 g/ml against Scedosporium apiospermum; 4 to 16 and >16 g/ml and 4 to 8 and 16 to >16 g/ml (ranges) against Scedosporium prolificans; and 16 and 16 g/ml and 4 and 4 g/ml against Fusarium spp. Isavuconazole showed minimal fungicidal concentrations for 50% and 90% of the isolates of 1 and 1 g/ml against Aspergillus, 16 and >16 g/ml against Candida, and 4 and >16 g/ml against Zygomycetes, respectively, and >16 g/ml against the remaining molds. The Etest proved to be a suitable alternative method for determining the antifungal activities of isavuconazole against Aspergillus and Candida; the Etest results showed 96% and 93% agreement with the results of the CLSI M38-A and M27-A2 methods, respectively.

Secondary resistance to azoles in Aspergillus fumigatus isolates from patients taking long-term itraconazole therapy has been described. We studied the acquisition of secondary azole resistance in 20 A. fumigatus isolates with no mutations at codon 54, 98, 138, 220, 432, or 448 in the cyp51A gene. Adjusted conidium inocula (3 ؋ 10 7 CFU/ml) of each isolate were prepared and progressively or directly exposed to increasing itraconazole concentrations, ranging from 0.5 g/ml to 16 g/ml. Itraconazole, voriconazole, and posaconazole MICs were determined using the CLSI M38-A2 procedure before (MIC initial ) and after (MIC final ) exposure to itraconazole. In both procedures, the MIC final was significantly higher than the MIC initial . However, after progressive exposure to itraconazole, the MICs of the three azoles were higher than after direct exposure. No mutations were found at codon 54, 98, 138, 220, 432, or 448 in the cyp51A gene of isolates growing at the highest concentration of itraconazole. More concentrated conidium inocula (2 ؋ 10 9 CFU/ml) plated in itraconazole at 4 g/ml revealed the presence of heteroresistant populations in two initially wild-type isolates. These isolates became resistant to itraconazole and posaconazole only after use of the concentrated inoculum. These heteroresistant isolates harbored a mutation at codon G54, and the MICs of itraconazole and posaconazole were >16 g/ml. In all procedures, A. fumigatus short tandem repeat (STRAf) typing was used to demonstrate that the genotype did not change before or after exposure to itraconazole.