Multi-strain probiotics for extremely preterm infants: a randomized controlled trial.

BACKGROUND: Effects of probiotics on intestinal microbiota and feeding tolerance remain unclear in extremely low-birth-weight (ELBW) infants. METHODS: ELBW infants were randomly assigned to receive probiotics or no intervention. Stool samples were collected prior to, 2 and 4 weeks after initiation, and 2 weeks after probiotics cessation for infants in the probiotics group, and at matched postnatal age time points for infants in the control group. RESULTS: Of the 102 infants assessed for eligibility, sixty-two were included. Infants who received probiotics reached full enteral feeds sooner (Mean difference (MD) -1.8; 95% CI:-3.7 to -0.01 day), had a tendency toward lower incidence of hematochezia before hospital discharge (22.6% vs 3.2%; P = 0.053), and were less likely to require extensively hydrolyzed- or amino acids-based formulas to alleviate signs of cow's milk protein intolerance in the first 6 months of life (19.4% vs 51.6%; P = 0.008). Infants on probiotics were more likely to receive wide-spectrum antibiotics (64.5% vs 32.2%; P = 0.01). Multi-strain probiotics resulted in significant increase in fecal Bifidobacterium (P < 0.001) and Lactobacillus (P = 0.005), and marked reduction in fecal candida abundance (P = 0.04). CONCLUSION: Probiotics sustained intestinal Bifidobacterium and reduced time to achieve full enteral feeds in extremely preterm infants. Probiotics might improve tolerance for cow's milk protein supplements. CLINICAL TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT03422562). IMPACT: Probiotics may help extremely preterm infants achieve full enteral feeds sooner. Probiotics may improve tolerance for cow's milk protein supplements. Multi-strain probiotics can sustain intestinal Bifidobacterium and Lactobacillus until hospital discharge.

Use of Molecular Methods To Detect Shigella and Infer Phenotypic Resistance in a Shigella Treatment Study.

Molecular diagnostic methods improve the detection of Shigella, yet their ability to detect Shigella drug resistance on direct stool specimens is less clear. We tested 673 stool specimens from a Shigella treatment study in Bangladesh, including 154 culture-positive stool specimens and their paired Shigella isolates. We utilized a TaqMan array card that included quantitative PCR (qPCR) assays for 24 enteropathogens and 36 antimicrobial resistance (AMR) genes. Shigella was detected by culture in 23% of stool specimens (154/673), while qPCR detected Shigella at diarrhea-associated quantities in 49% (329/673; P < 0.05). qPCR for AMR genes on the Shigella isolates yielded >94% sensitivity and specificity compared with the phenotypic susceptibility results for azithromycin and ampicillin. The performance for trimethoprim-sulfamethoxazole susceptibility was less robust, and the assessment of ciprofloxacin was limited because most isolates were resistant. The detection of AMR genes in direct stool specimens generally yielded low specificities for predicting the resistance of the paired isolate, whereas the sensitivity and negative predictive values for predicting susceptibility were often higher. For example, the detection of ermB or mphA in stool yielded a specificity of 56% but a sensitivity of 91% and a negative predictive value of 91% versus the paired isolate's azithromycin resistance result. Patients who received azithromycin prior to presentation were universally culture negative (0/112); however, qPCR still detected Shigella at diarrhea-associated quantities in 34/112 (30%). In sum, molecular diagnostics on direct stool specimens greatly increase the diagnostic yield for Shigella, including in the setting of prior antibiotics. The molecular detection of drug resistance genes in direct stool specimens had low specificity for confirming resistance but could potentially "rule out" macrolide resistance.