Vitamin D supplementation to persistent carriers of MRSA-a randomized and placebo-controlled clinical trial.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to all beta-lactam antibiotics and can cause severe infections that are difficult to treat. Eradication strategies with conventional antibiotics are not always effective and alternative approaches are warranted. Here, we tested the hypothesis that daily supplementation with vitamin D for 12 months would reduce MRSA carriage rates among a group of persistent carriers. This was a double-blind, placebo-controlled randomized trial with n = 65 persistent MRSA carriers with 25-hydroxy vitamin D3 (25OHD) < 75 nmol/L, who were followed up with bacterial cultures at baseline and every 3 months for 1 year. The primary endpoint was the decline in MRSA positivity during the study period. The study was conducted in two MRSA outpatient clinics at the Karolinska University Hospital, Stockholm, Sweden. In total, n = 65 persistent MRSA carriers were randomized and n = 3 were lost to follow-up. Only patients deficient in vitamin D (< 75 nmol/L) were included. Vitamin D (4000 IU) or placebo/day was administered for 12 months. The decline in MRSA positivity was equal in the vitamin D and placebo group during the study period (OR, 1.00; 95% CI, 0.97-1.03; p = 0.928) and approximately 40% in both groups were MRSA-negative after 12 months. The vitamin D group produced 103 positive cultures out of 318 cultures (32.4%) from nose, throat, and perineum over the study period, whereas the placebo group produced 135/393 positive cultures (34.0%) (Fisher's exact test, p = 0.94). Vitamin D supplementation did not influence MRSA carriage. Thus, available data does not support vitamin D supplementation to persistent MRSA carriers.Trial registration: www.clinicaltrials.gov ; NCT02178488.

[Do not overuse doxycycline as prophylaxis for uncomplicated sexually transmitted infections]. / Överanvänd inte doxycyklin som profylax mot STI.

STI prophylaxis using doxycycline is discussed internationally for persons at high risk of STIs (Doxy-PEP). Doxy-PEP would probably have limited effect on gonorrhoea due to resistance to tetracyclines. Doxy-PEP may reduce the incidence of chlamydia and syphilis, but would not reduce the number of complicated infections. Further studies are needed on the effects of intermittent antibiotic use on the microbiome or antibiotic resistance in general.

Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1.

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

The microbial metabolite trimethylamine-N-oxide in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages.

OBJECTIVE: HIV-1-infection infers an increased cardiovascular risk where gut dysbiosis and microbial translocation may contribute. We assessed TMAO, a microbial metabolite with atherosclerotic properties, in plasma of HIV-1-infected individuals at different clinical stages in relation to inflammatory markers, cardiovascular events and gut microbiota. METHODS: Primary HIV-1-infected (n = 17) and chronic HIV-1-infected individuals (n = 22) were sampled before and after ART-initiation. In the chronic HIV-1-cohort, repeated faecal samples were analysed by 16SrRNA gene sequencing. HIV-1-infected individuals on longstanding ART (n = 101) and healthy HIV-1-negative individuals (n = 60), served as controls. TMAO and markers of immune activation were analysed by LC/MS/MS and immune assays, respectively. RESULTS: TMAO levels were lower in untreated HIV-1-infected individuals, increased significantly after ART-initiation (P = 0.040 and P < 0.001) but remained similar to healthy controls. TMAO levels were not affected by ART, immune status or degree of systemic inflammation. Higher TMAO in HIV-1-infected individuals on longstanding ART was not significantly associated with cardiovascular risk (P = 0.38). Additionally, TMAO levels correlated inversely with Bacteroidetes (Rho: -0.62, P = 0.002), and positively with Firmicutes (Rho: 0.65, P = 0.001) but held no correlation to TMA-producing genera. Notably gut dysbiosis at follow-up was more pronounced in patients without increase in TMAO levels after ART characterized by loss of Bacteroidetes (P = 0.023) and significantly elevated LPS levels (P = 0.01). CONCLUSION: Our data does not support that TMAO is a significant link between gut dysbiosis and inflammation in HIV-1-infection. We propose that HIV-1, microbial composition and ART disparately confound TMAO levels, thus limiting its role as a cardiovascular risk marker in HIV-1-infected individuals.

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease.

BACKGROUND: The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. OBJECTIVE: To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. METHODS: Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3-5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. RESULTS: GFR was the dominant variable affecting TMAO (ß = -0.41; p<0.001), choline (ß = -0.38; p<0.001), and betaine (ß = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3-5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32-14.2; p = 0.016). CONCLUSION: Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3-5 patients.