[Show abstract][Hide abstract] ABSTRACT: Recent studies suggest that immune-modulating single nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related
infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of Invasive Aspergillosis
(IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association
study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs were associated with an increased risk of IA (OR=1.92, 95%CI: 1.20-3.09 and OR=1.73, 1.06-2.81) whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (OR=0.60, 0.38-0.96 and OR=0.63,
0.41-0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect
observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (OR=5.63, 1.20-3.09 and OR=0.24, 0.10-0.59) than in non-HSCT patients, suggesting that the
presence of these SNPs may render patients more vulnerable to infection especially under severe and prolonged immunosuppressive
conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralisation of fungal conidia (P=0.0003) and, under stimulation conditions, produced higher levels of IFNγ mRNA (P=0.049) and IFNγ and TNFα cytokines (PLPS-96h=0.057, PPHA-96h=0.036 and PLPS+PHA-96h=0.030 and PPHA-72h=0.045, PLPS+PHA-72h=0.018, PLPS-96h=0.058 and PLPS+PHA-96h=0.0058, respectively). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including
clinical variables led to a substantial improvement in the discriminatory ability to predict the disease (AUC=0.659 vs. AUC=0.564,
PLR=5.2•10-4 and P50.000Perm=9.34•10-5). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70 and VEGFα variants might be used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.
Full-text · Article · Dec 2015 · Infection and immunity
[Show abstract][Hide abstract] ABSTRACT: Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.
Full-text · Article · Sep 2015 · Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia