Key Points Question Are 2 core Infectious Diseases Society of America–recommended antimicrobial stewardship strategies, preauthorization (PA) and postprescription audit and review (PPR), feasible in community hospitals? Findings Among 2692 patients in this multicenter nonrandomized clinical trial with crossover design, PPR and a modified PA strategy were feasible; strict PA was not feasible. Postprescription audit and review decreased antimicrobial use and identified more inappropriate antimicrobial therapy, led to more direct interactions with clinicians, and resulted in more antimicrobial de-escalation than the modified PA strategy. Meaning Postprescription audit and review is a feasible and effective strategy for antimicrobial stewardship in settings with limited resources and expertise.

BackgroundThe rate of community-acquired Clostridium difficile infection (CA-CDI) is increasing. While receipt of antibiotics remains an important risk factor for CDI, studies related to acquisition of C. difficile outside of hospitals are lacking. As a result, risk factors for exposure to C. difficile in community settings have been inadequately studied.Main objectiveTo identify novel environmental risk factors for CA-CDIMethodsWe performed a population-based retrospective cohort study of patients with CA-CDI from 1/1/2007 through 12/31/2014 in a 10-county area in central North Carolina. 360 Census Tracts in these 10 counties were used as the demographic Geographic Information System (GIS) base-map. Longitude and latitude (X, Y) coordinates were generated from patient home addresses and overlaid to Census Tracts polygons using ArcGIS; ArcView was used to assess “hot-spots” or clusters of CA-CDI. We then constructed a mixed hierarchical model to identify environmental variables independently associated with increased rates of CA-CDI.ResultsA total of 1,895 unique patients met our criteria for CA-CDI. The mean patient age was 54.5 years; 62% were female and 70% were Caucasian. 402 (21%) patient addresses were located in “hot spots” or clusters of CA-CDI (p<0.001). “Hot spot” census tracts were scattered throughout the 10 counties. After adjusting for clustering and population density, age ≥ 60 years (p = 0.03), race (<0.001), proximity to a livestock farm (0.01), proximity to farming raw materials services (0.02), and proximity to a nursing home (0.04) were independently associated with increased rates of CA-CDI.ConclusionsOur study is the first to use spatial statistics and mixed models to identify important environmental risk factors for acquisition of C. difficile and adds to the growing evidence that farm practices may put patients at risk for important drug-resistant infections.

Eggs from reciprocal hybrids between the C57BL/6By and BALB/cBy strains were tested for their susceptibility to attack by hyaluronidase and pronase. There were significant reciprocal differences between the F 1 females in the responses of their unfertilized eggs to both enzymes. The F x hybrids from BALB mothers showed the increased susceptibility characteristic of C57BL whilst the F x hybrids with C57BL mothers were more resistant to both enzymes, like BALB mice. Eggs from the four kinds of reciprocal F 2 hybrid females also showed patroclinous patterns of susceptibility. A patroclinous difference was found between reciprocal crosses of the CXBD and CXBE recombinant inbred strains but not in crosses between recombinant inbred strains with similar phenotypes. Cross fostering did not alter the phenotypes of the C57BL and BALB females or those of their reciprocal F 1 hybrids. The findings are interpreted in terms of differential genomic imprinting of paternally inherited information. The possible general usefulness of patroclinous differences between reciprocal F x females in revealing differences in imprinting is noted.

The cumulus oophorus surrounding eggs from C57BL/6 mice was digested by bovine or leech hyaluronidase significantly more rapidly than that surrounding eggs from BALB/c mice. The zona pellucida of C57BL/6 eggs was also more rapidly attacked by pronase. Three other sublines of C57BL showed the same characteristics. Measurements of susceptibility to hyaluronidase and pronase on eggs from the CXB recombinant inbred strains indicated that variation at a minimum of 2 loci affected each character. The lack of correlation between susceptibilities to the 2 enzymes across the recombinant strains implied that these differences separately affect the substrates of the enzymes, rather than reflecting a common difference in the process of oocyte maturation. The variation in susceptibility was unrelated to differences, controlled by the Ped and Qa-2 loci, in the rate of later embryonic cleavage. However, pronase susceptibility was significantly correlated with the early onset of the first cleavage.