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

Abstract

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.

Keywords: Clinical trial; Immunity; Methicillin-resistant S. aureus (MRSA); Vitamin D.

Conflict of interest statement

Conflict of interest

The authors do not have any conflict of interests in relation to the current work.

Access to data

The first (LBB) and last author (PB) have full access to data and are the guarantor of data integrity.

Figures

Fig. 1

CONSORT chart

Fig. 2

The primary endpoint was the slope of the probability to carry MRSA, based on values for baseline, 3, 6, 9, and 12 months. The model included subjects as random effect, time (in weeks) as a continuous variable, and an interaction between time and treatment group. The colored area represents the 95% confidence interval; yellow is for the vitamin D group and orange is for the placebo group

Fig. 3

Serum levels of 25-OH vitamin D during the study. Error bars depict standard error of the mean (SEM)

Fig. 4

The effect of vitamin D supplementation in different subgroups was tested by interaction-analysis between time, allocation, and various pre-specified risk factors for MRSA carriage. The results are presented in a forest plot where the square represents the point estimate and the line is the 95% confidence interval. If the line crosses the perpendicular line for OR = 1.0, the effect is not significant

Fig. 5

N = 6 study participants that were given anti-MRSA antibiotics during the study period are depicted as P1–P6, followed by a “P” for placebo and “D” for vitamin D. The patients were sampled for bacterial cultures (nose, throat, and perineum) for every 3 months from baseline until 12 months. MRSA-positive cultures are shown as filled circles, MRSA-negative cultures are shown as open circles, and anti-MRSA antibiotics are shown as black triangles