Multistrain probiotics do not reduce multidrug-resistant organisms in preemies

In preterm infants, the use of multistrain probiotics does not appear to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+), as shown in the phase III PRIMAL* trial.

PRIMAL included 643 infants with gestational age of 28 to 32 weeks at 18 German neonatal units. These infants were randomly assigned to receive multistrain probiotics or placebo diluted in human milk/formula, administered within the first 72 hours of life for a total of 28 days.

The primary endpoint was colonization with MDRO+ at day 30 of life, while safety endpoints included late-onset sepsis and severe gastrointestinal complication. Gut dysbiosis was also assessed.

A total of 618 infants (median gestational age 31.0 weeks, 53.9 percent male, mean birth weight 1,502 g) had follow-up at day 30.

Interim analysis, which included available data from 219 infants, showed that the incidence of MDRO+ colonization was similar between the probiotics and the control group (37.4 percent vs 37.5 percent; adjusted risk ratio, 0.99, 95 percent confidence interval [CI], 0.54–1.81; p=0.97).

Likewise, safety outcomes did not significantly differ between the treatment groups. Late-onset sepsis occurred in 8 of 316 infants in the probiotics group and in 12 of 322 infants in the control group (2.5 percent vs 3.7 percent), while severe gastrointestinal complications were documented in six and seven infants in the respective groups (1.9 percent vs 2.2 percent).

However, compared with the control group, the probiotics group had higher eubiosis scores at the genus level (median scores, 0.47 vs 0.41; odds ratio [OR], 1.07; 95% CI, 1.02–1.13) and at the species level (median scores, 0.87 vs 0.59; OR, 1.28, 95 percent CI, 1.19–1.38).

Roughly half of infants (49 percent) in the control group acquired the B infantis probiotic strain from the environment, with rates varying widely between study sites. This was especially common among infants whose siblings received probiotic treatment.

*Priming Immunity at the Beginning of Life