Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI.

We are moderately confident that antibiotic treatment leads to antibiotic resistance development in neonates and it may also induce potentially disease-promoting gut microbiota alterations. Our findings emphasize the need to reduce unnecessary antibiotic treatment in neonates.

Objectives: In 2014 probiotic supplementation (Lactobacillus acidophilus and Bifidobacterium longum subspecies infantis; InfloranⓇ) was introduced as standard of care to prevent necrotizing enterocolitis (NEC) in extremely preterm infants in Norway. We aimed to evaluate the influence of probiotics and antibiotic therapy on the developing gut microbiota and antibiotic resistome in extremely preterm infants, and to compare with very preterm infants and term infants not given probiotics.Study design: A prospective, observational multicenter study in six tertiary-care neonatal units. We enrolled 76 infants; 31 probiotic-supplemented extremely preterm infants <28 weeks gestation, 35 very preterm infants 28–31 weeks gestation not given probiotics and 10 healthy full-term control infants. Taxonomic composition and collection of antibiotic resistance genes (resistome) in fecal samples, collected at 7 and 28 days and 4 months age, were analyzed using shotgun-metagenome sequencing.Results: Median (IQR) birth weight was 835 (680–945) g and 1,290 (1,150–1,445) g in preterm infants exposed and not exposed to probiotics, respectively. Two extremely preterm infants receiving probiotic developed NEC requiring surgery. At 7 days of age we found higher median relative abundance of Bifidobacterium in probiotic supplemented infants (64.7%) compared to non-supplemented preterm infants (0.0%) and term control infants (43.9%). Lactobacillus was only detected in small amounts in all groups, but the relative abundance increased up to 4 months. Extremely preterm infants receiving probiotics had also much higher antibiotic exposure, still overall microbial diversity and resistome was not different than in more mature infants at 4 weeks and 4 months.Conclusion: Probiotic supplementation may induce colonization resistance and alleviate harmful effects of antibiotics on the gut microbiota and antibiotic resistome.Clinical Trial Registration: Clinicaltrials.gov: NCT02197468. https://clinicaltrials.gov/ct2/show/NCT02197468

Bifidobacteria are commensals that colonize the orogastrointestinal tract and rarely cause invasive human infections. However, an increasing number of bifidobacterial blood culture isolates has lately been observed in Norway. In order to investigate the pathogenicity of the Bifidobacterium species responsible for bacteremia, we studied Bifidobacterium isolates from 15 patients for whom cultures of blood obtained from 2013 to 2015 were positive. We collected clinical data and analyzed phenotypic and genotypic antibiotic susceptibility. All isolates (11 Bifidobacterium longum, 2 B. breve, and 2 B. animalis isolates) were subjected to whole-genome sequencing. The 15 patients were predominantly in the extreme lower or upper age spectrum, many were severely immunocompromised, and 11 of 15 had gastrointestinal tract-related conditions. In two elderly patients, the Bifidobacterium bacteremia caused a sepsis-like picture, interpreted as the cause of death. Most bifidobacterial isolates had low MICs (Յ0.5 mg/liter) to beta-lactam antibiotics, vancomycin, and clindamycin and relatively high MICs to ciprofloxacin and metronidazole. We performed a pangenomic comparison of invasive and noninvasive B. longum isolates based on 65 sequences available from GenBank and the sequences of 11 blood culture isolates from this study. Functional annotation identified unique genes among both invasive and noninvasive isolates of Bifidobacterium. Phylogenetic clusters of invasive isolates were identified for a subset of the B. longum subsp. longum isolates. However, there was no difference in the number of putative virulence genes between invasive and noninvasive isolates. In conclusion, Bifidobacterium has an invasive potential in the immunocompromised host and may cause a sepsis-like picture. Using comparative genomics, we could not delineate specific pathogenicity traits characterizing invasive isolates.KEYWORDS DNA sequencing, antibiotic resistance, bifidobacteria, blood culture, bloodstream infections, mass spectrometry, pangenome, probiotics, susceptibility testing, virulence factors B ifidobacteria are anaerobic, nonsporulating Gram-positive rods representing ubiquitous inhabitants of the human orogastrointestinal tract and vagina. The genus consists of more than 50 species, with only 10 species being found in humans. In breast-fed infants, bifidobacteria constitute more than 80% of the intestinal microbiota, whereas bifidobacteria comprise only 3 to 6% of the adult fecal flora (1, 2). Moreover, the species distribution is different in infants and adults; Bifidobacterium adolescentis and Bifidobacterium longum subsp. longum are the major bifidobacterial species in the

No abstract

15The primary aim of this study was to determine antimicrobial resistance in coagulase negative staphylococci (CoNS) from healthy 16 adults in the community. Healthy adults (n=114) were swabbed on six body sites; both armpits, both knee pits and both sides of the 17 groin. Species determination was performed using MALDI-TOF and susceptibility testing for eleven relevant antimicrobials was 18 performed by the disc diffusion method and minimal inhibitory concentration gradient test. 19In total, 693 CoNS-isolates were identified. Susceptibility testing was done on 386 isolates; one CoNS from each species found on 20 each participant from the different body sites. The prevalence of antimicrobial resistance in the CoNS isolates were; erythromycin 21 (24.6%), fusidic acid (19.9%), tetracycline (11.4%),clindamycin (7.8%), gentamicin (6.2%) and cefoxitin (4.1%). Multidrug resistance 22 was observed in 5.7% of the isolates. Staphylococcus epidermidis and S. hominis were the first and second most prevalent species on 23 all three body sites. We conclude that CoNS isolates from healthy adults in the community have a much lower prevalence of 24 antimicrobial resistance than reported in nosocomial CoNS isolates. Still, we believe that levels of resistance in community CoNS 25 should be monitored as the consumption of antimicrobials in primary care in Norway is increasing. 26 27Running head: Antimicrobial susceptibility of community coagulase negative staphylococci . 28

No abstract

No abstract