Clostridium difficile infection (C. difficile; CDI) is the most common hospital-acquired infection in the United States, where it is responsible for over 15,000 deaths and five billion dollars in direct healthcare costs annually. This study evaluates the cost effectiveness of nine infection control interventions at reducing the rates of hospital-onset CDI. Cost-effectiveness analyses were conducted from the hospital perspective, where all costs were converted into 2017 US dollars and effectiveness was measured using quality-adjusted life years (QALYs). The nine tested interventions include daily and terminal cleaning with sporicidal product, patient, visitor, and healthcare worker hand hygiene, reducing patient room transfers, screening for C. difficile colonization at admission, and visitor and healthcare worker contact precautions. Rates of hospital-onset CDI were estimated using our recently published agent-based simulation model of C. difficile transmission in a general 200-bed adult hospital. Cost and utility estimates were derived from the literature. Six interventions were dominant, compared to baseline standard hospital practices: daily cleaning (saved an average of $407,853 and 26.8 QALYs annually in a 200-bed hospital), screening at admission ($9,143; 13.5 QALYs), patient hand hygiene ($25,699; 4.6 QALYs), healthcare worker hand hygiene ($181,784; 12.9 QALYs), terminal cleaning ($65,007; 9.3 QALYs), and patient transfer ($25,677; 2.3 QALYs). Healthcare worker contact precautions had a mean ICER of $147,666/QALY. Visitor hand hygiene had a mean ICER of $8,541,937/QALY. Visitor contact precautions was dominated. Healthcare facilities are a major source of CDI and hospital prevention is critical to decreasing its overall incidence. This is the first study to compare the cost-effectiveness of patient-centered interventions, such as patient hand hygiene and screening at admission, with conventional hospital-centered strategies. Prioritizing highly effective, cost saving interventions such as daily and terminal cleaning is a promising strategy that should be further emphasized in future C. difficile prevention guidelines.

A retrospective cohort study was conducted to evaluate the utility of self-reported tobacco use for developing a clinical prediction rule for poor outcomes of Clostridium difficile infection. Patients with any history of smoking were significantly less likely than never smokers to be cured of their infection within two weeks. Disease recurrence, readmission within 30 days, death before treatment completion, and the severity of Clostridium difficile infection were not associated with smoking status.

Perturbations in the gastrointestinal microbiome caused by antibiotics are a major risk factor for Clostridium difficile infection (CDI). Probiotics are often recommended to mitigate CDI symptoms; however, there exists only limited evidence showing probiotic efficacy for CDI. Here, we examined changes to the GI microbiota in a study population where probiotic treatment was associated with significantly reduced duration of CDI diarrhea. Subjects being treated with standard of care antibiotics for a primary episode of CDI were randomized to probiotic treatment or placebo for 4 weeks. Probiotic treatment consisted of a daily multi-strain capsule (Lactobacillus acidophilus NCFM, ATCC 700396; Lactobacillus paracasei Lpc-37, ATCC SD5275; Bifidobacterium lactis Bi-07, ATCC SC5220; Bifidobacterium lactis B1-04, ATCC SD5219) containing 1.7 x 1010 CFUs. Stool was collected and analyzed using 16S rRNA sequencing. Microbiome analysis revealed apparent taxonomic differences between treatments and timepoints. Subjects administered probiotics had reduced Verrucomicrobiaceae at week 8 compared to controls. Bacteroides were significantly reduced between weeks 0 to 4 in probiotic treated subjects. Ruminococcus (family Lachnospiraceae), tended to be more abundant at week 8 than week 4 within the placebo group and at week 8 than week 0 within the probiotic group. Similar to these results, previous studies have associated these taxa with probiotic use and with mitigation of CDI symptoms. Compositional prediction of microbial community function revealed that subjects in the placebo group had microbiomes enriched with the iron complex transport system, while probiotic treated subjects had microbiomes enriched with the antibiotic transport system. Results indicate that probiotic use may impact the microbiome function in the face of a CDI; yet, more sensitive methods with higher resolution are warranted to better elucidate the roles associated with these changes. Continuing studies are needed to better understand probiotic effects on microbiome structure and function and the resulting impacts on CDI.

Restricted accessAbstractFirst published online March 1, 2016Social Determinants of Patient Antibiotic Misuse in Haryana, IndiaA Barker, K Verhoeven, […], M Ahsan, S Alam, P Sharma, S Sengupta, and N Safdar+4-4View all authors and affiliationsVolume 64, Issue 4https://doi.org/10.1136/jim-2016-000120.49

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.