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Background The number of adults afflicted with community-associated Clostridium difficile infection (CA-CDI) has increased dramatically over the past 10 years. Exposure to infants, a population known to be asymptomatically colonized by C. difficile (CD), has been identified as a risk factor for CA-CDI, implying that infants may be a reservoir for adult infection. In the present study, we determined the distribution of CD ribotypes isolated from adults with CA-CDI and compared them to the ribotypes of strains excreted asymptomatically among a cohort of healthy infants from the same geographical location. Methods Adult samples submitted to a referral university hospital microbiology laboratory as part of routine care were identified as CD+ by commercial PCR and stored at −80°; the subset of samples from patients meeting IDSA criteria for CA-CDI were selected for further analysis. A cohort of healthy infants attending a suburban, demographically diverse pediatric practice 6 miles from the hospital were enrolled at birth and prospectively followed at 2-, 6-, and 12-month well-visits. Stool collected at each infant visit was cultivated for CD using routine techniques. DNA from both sets of organisms was extracted and subjected to fluorescent PCR ribotyping. Amplicons were assigned to specific ribotypes through sequence analysis, using the nomenclature proposed previously (J Clin Microbiol 2015;53:1192). Results To date, 29 adult samples (collected between August 1, 2016 and January 31, 2018) and 32 infant samples (collected between July 1, 2016 and March 31, 2018) have been ribotyped. Eleven (18%) organisms could not be typed (3 adult; 8 infant). The most representative ribotype identified in the adult CA-CDI samples was F014-020 (54%), with small numbers scattered among six other ribotypes. The most prominent ribotypes in infants were F106 (33%), F010 (17%), and F012 (17%); two (8%) infants were colonized with ribotype F014-020. Except for F014-020, there was no concordance of ribotypes among adult CA-CDI and infant isolates. Conclusion In this population, a small proportion of asymptomatic infants were colonized by a prominent CA-CDI ribotype in adults, but other ribotypes were unique to each age group. Disclosures All authors: No reported disclosures.

The density of native (preexisting) collaterals and their capacity to enlarge into large conduit arteries in ischemia (arteriogenesis) are major determinants of the severity of tissue injury in occlusive disease. Mechanisms directing arteriogenesis remain unclear. Moreover, nothing is known about how native collaterals form in healthy tissue. Evidence suggests vascular endothelial growth factor (VEGF), which is important in embryonic vascular patterning and ischemic angiogenesis, may contribute to native collateral formation and arteriogenesis. Therefore, we examined mice heterozygous for VEGF receptor-1 (VEGFR-1 +/− ), VEGF receptor-2 (VEGFR-2 +/− ), and overexpressing (VEGF hi/+ ) and underexpressing VEGF-A (VEGF lo/+ ). Recovery from hindlimb ischemia was followed for 21 days after femoral artery ligation. All statements below are P +/− showed similar: ischemic scores, recovery of hindlimb perfusion, pericollateral leukocytes, collateral enlargement, and angiogenesis. In contrast, VEGFR-1 +/− showed impaired: perfusion recovery, pericollateral leukocytes, collateral enlargement, worse ischemic scores, and comparable angiogenesis. Compared to wild-type mice, VEGF lo/+ had 2-fold lower perfusion immediately after ligation (suggesting fewer native collaterals which was confirmed by angiography) and blunted recovery of perfusion. VEGF hi/+ mice had 3-fold greater perfusion immediately after ligation, more native collaterals, and improved recovery of perfusion. These differences were confirmed in the cerebral pial cortical circulation where, compared to VEGF hi/+ mice, VEGF lo/+ formed fewer collaterals during the perinatal period when adult density was established, and had 2-fold larger infarctions after middle cerebral artery ligation. Our findings indicate VEGF and VEGFR-1 are determinants of arteriogenesis. Moreover, we describe the first signaling molecule, VEGF-A, that specifies formation of native collaterals in healthy tissues.