Artificial Differences in Clostridium difficile Infection Rates Associated with Disparity in Testing.

In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.

Costs of healthcare- and community-associated infections with antimicrobial-resistant versus antimicrobial-susceptible organisms.

OBJECTIVE: We compared differences in the hospital charges, length of hospital stay, and mortality between patients with healthcare- and community-associated bloodstream infections, urinary tract infections, and pneumonia due to antimicrobial-resistant versus -susceptible bacterial strains. METHODS: A retrospective analysis of an electronic database compiled from laboratory, pharmacy, surgery, financial, and patient location and device utilization sources was undertaken on 5699 inpatients who developed healthcare- or community-associated infections between 2006 and 2008 from 4 hospitals (1 community, 1 pediatric, 2 tertiary/quaternary care) in Manhattan. The main outcome measures were hospital charges, length of stay, and mortality among patients with antimicrobial-resistant and -susceptible infections caused by Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. RESULTS: Controlling for multiple confounders using linear regression and nearest neighbor matching based on propensity score estimates, resistant healthcare- and community-associated infections, when compared with susceptible strains of the same organism, were associated with significantly higher charges ($15,626; confidence interval [CI], $4339-$26,913 and $25,573; CI, $9331-$41,816, respectively) and longer hospital stays for community-associated infections (3.3; CI, 1.5-5.4). Patients with resistant healthcare-associated infections also had a significantly higher death rate (0.04; CI, 0.01-0.08). CONCLUSIONS: With careful matching of patients infected with the same organism, antimicrobial resistance was associated with higher charges, length of stay, and death rates. The difference in estimates after accounting for censoring for death highlight divergent social and hospital incentives in reducing patient risk for antimicrobial resistant infections.

Comparison of two computer algorithms to identify surgical site infections.

BACKGROUND: Surgical site infections (SSIs), the second most common healthcare-associated infections, increase hospital stay and healthcare costs significantly. Traditional surveillance of SSIs is labor-intensive. Mandatory reporting and new non-payment policies for some SSIs increase the need for efficient and standardized surveillance methods. Computer algorithms using administrative, clinical, and laboratory data collected routinely have shown promise for complementing traditional surveillance. METHODS: Two computer algorithms were created to identify SSIs in inpatient admissions to an urban, academic tertiary-care hospital in 2007 using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes (Rule A) and laboratory culture data (Rule B). We calculated the number of SSIs identified by each rule and both rules combined and the percent agreement between the rules. In a subset analysis, the results of the rules were compared with those of traditional surveillance in patients who had undergone coronary artery bypass graft surgery (CABG). RESULTS: Of the 28,956 index hospital admissions, 5,918 patients (20.4%) had at least one major surgical procedure. Among those and readmissions within 30 days, the ICD-9-CM-only rule identified 235 SSIs, the culture-only rule identified 287 SSIs; combined, the rules identified 426 SSIs, of which 96 were identified by both rules. Positive and negative agreement between the rules was 36.8% and 97.1%, respectively, with a kappa of 0.34 (95% confidence interval [CI] 0.27-0.41). In the subset analysis of patients who underwent CABG, of the 22 SSIs identified by traditional surveillance, Rule A identified 19 (86.4%) and Rule B identified 13 (59.1%) cases. Positive and negative agreement between Rules A and B within these "positive controls" was 81.3% and 50.0% with a kappa of 0.37 (95% CI 0.04-0.70). CONCLUSION: Differences in the rates of SSI identified by computer algorithms depend on sources and inherent biases in electronic data. Different algorithms may be appropriate, depending on the purpose of case identification. Further research on the reliability and validity of these algorithms and the impact of changes in reimbursement on clinician practices and electronic reporting is suggested.

Theory based analysis of anti-inflammatory effect of infliximab on Crohn's disease.

Tumor necrosis factor (TNF)-alpha, a primary mediator of inflammatory responses, is increased in patients with active Crohn's disease (CD) and considered to play an important role in the regulation of inflammation in CD. Infliximab (IFX) is a chimeric murine-human monoclonal IgG1 antibody that targets TNF-alpha and is used as a therapeutic agent for CD. Although that dosage regimen has been established through clinical trial experience, it has not been analyzed theoretically. We analyzed of sequential changes of the Crohn's disease activity index (CDAI) using a pharmacokinetic-pharmacodynamic model integrating the pharmacokinetics of IFX and turnover rate of TNF-alpha. The time course effects of IFX derived from the present model were matched to reported data regarding CDAI ratios, and we found that the clinical effect of IFX reached a maximum value 2 to 4 weeks after administration and was maintained for the next several weeks. Our results suggested that the standard dosage regimen of IFX is theoretically appropriate. Further, based on the results of various dosage regimens, a second administration of IFX 2 weeks after the first dose was shown to achieve remission in the early stage of active CD, when IFX was given as a repeated treatment.

Analysis of linkage between lymphotoxin alpha haplotype and polymorphisms in 5'-flanking region of tumor necrosis factor alpha gene associated with efficacy of infliximab for Crohn's disease patients.

Tumor necrosis factor (TNF)alpha is increased in patients with Crohn's disease (CD) and considered to play an important role in the inflammation. Infliximab (IFX) is used as a therapeutic agent for CD. Recently, it was reported that homozygosity for a lymphotoxin alpha (LTA) haplotype (LTA 1-1-1-1) may identify subgroups with a poor response to IFX. In the present study, we characterized the linkage of the LTA haplotype with SNPs in the 5'-flanking region of the TNFalpha gene. In subjects who had homozygosity for each LTA haplotype, 6 nucleotide variations, -857C > T, -522C > G, -357A > C, -261C > G, -159G > T and -96G > T, were found in the 5'-flanking region of the TNFalpha gene. As for linking with the allele, only -857T met the LTA haplotype 1-1-1-1. We concluded that the differences in therapeutic effects of IFX among patients with CD may be explained in part by the induction ability of TNFalpha via the -857C > T polymorphism.

Reverse genetic analyses of gamete-enriched genes revealed a novel regulator of the cAMP signaling pathway in Dictyostelium discoideum.

Sexual development in Dictyostelium discoideum is initiated by the fusion of opposite mating type cells to form zygote giant cells, which subsequently gather and phagocytose surrounding cells for nutrition to form macrocysts. Here we performed the targeting of 24 highly gamete-enriched genes we previously isolated, and successfully generated knockout mutants for 16 genes and RNAi mutants for 20 genes including 6 genes without disruptants. In the knockout mutants of two genes, cell aggregation toward the giant cells was much less extensive and many cells remained around poorly formed macrocysts. We named these genes tmcB and tmcC. Although macrocyst formation of wild type cells was suppressed by the addition of exogenous cAMP, that of knockout mutants of tmcB was much less sensitive. The mRNA level of phosphodiesterase (pde) was higher and that of its inhibitor (pdi) was lower in the latter cells compared to the parental strains during sexual development. Thus, tmcB appeared to be a novel regulator of the cAMP signaling pathway specific to sexual development. Knockout mutants of tmcC were indistinguishable from the wild type cells with respect to the cAMP response, suggesting that this gene is relevant to other processes.