These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Background: Streptococcus mutans is a major cause of dental caries. Its capacity to produce bio lm is fundamental in the pathogenesis of this ubiquitous condition. As maintaining a healthy dentition is a genuine goal given the contemporary advance in caries control, researchers are striving to achieve a breakthrough in caries therapy. We are taking the anti-cariogenic properties of vitamin C a step-further, considering the well-known evidence of the inversely proportionate relationship between salivary levels of vitamin C and dental caries. The aim of this study was to determine MIC, MBC, bio lm prevention concentration (BPC), and derivative measures of vitamin C against fresh clinical isolates of S. mutans to evaluate its e cacy as an anti-cariogenic agent. Results: Based on the data of four independent experiments done in quadruplicates, we found a concentration-dependent inhibitory effect of vitamin C on all S. mutans strains tested. The average MBC, MIC, and BPC of vitamin C were found to be 10.16, 9.38, and 5.61 mg/ml, respectively. Spectrophotometric quantitation of crystal violet showed diminished bio lm formation in the presence of vitamin C (p < 0.05). When compared with gentamicin, vitamin C produced a zone of inhibition that was three times as large against the clinical isolates. Conclusion: Our results show that vitamin C has a negative effect on S. mutans growth and bio lm formation. Being the rst to meticulously utilize BPC to explore a well-known effect of vitamin C, this report aims to help in the instigation of trials of higher evidence that will ultimately culminate in repurposing vitamin C as a novel anti-cariogenic agent, albeit further studies are required to provide auxiliary evidence in this context.

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The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N-or O-linked mannosyl residues and an inner skeletal layer of β-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of β-glucan by the dectin-1/ TLR2 receptor complex. C. albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.

The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL. These tentative breakpoints are now open for public commentary.