Our study demonstrated that maternal-neonatal transmission of ESBL-E from mother to child is an important risk factor for colonization of VLBW infants. As a consequence, routine ESBL-E screening of neonates and mothers should be considered as a means of reducing neonatal morbidity and mortality.

Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H2O2, and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H2O2, as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium.

ObjectiveTo determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs).DesignA multi-center interrupted time series analysis.Setting44 German NICUs with routine use of dual-strain probiotics on neonatal ward level.PatientsPreterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014.InterventionRoutine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level.Main outcome measuresIncidences of NEC, overall mortality, mortality following NEC and nosocomial BSI.ResultsData from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38–0.62), overall mortality (HR = 0.60, 95% CI = 0.44–0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26–0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81–0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g.ConclusionIn order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards.

At present, Salmonella is considered to express two peroxiredoxin-type peroxidases, TsaA and AhpC. Here we describe an additional peroxiredoxin, Tpx, in Salmonella enterica and show that a single tpx mutant is susceptible to exogenous hydrogen peroxide (H 2 O 2 ), that it has a reduced capacity to degrade H 2 O 2 compared to the ahpCF and tsaA mutants, and that its growth is affected in activated macrophages. These results suggest that Tpx contributes significantly to the sophisticated defense system that the pathogen has evolved to survive oxidative stress.

In contrast to BSI due to ESBL-positive E. coli, cases of ESBL-positive K. pneumoniae BSI were associated with significantly increased costs and length of stay. Infection prevention measures should differentiate between both pathogens.