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Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.

ABSTRACT: We characterized clinically occurring and novel mutations in the ? subunit of RNA polymerase in Clostridium difficile (CdRpoB), conferring rifamycin (including rifaximin) resistance. The Arg505Lys substitution did not impose an in vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of CdRpoB. In general, most mutations lacked in vitro fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic.

SUBMITTER: Dang UT

PROVIDER: S-EPMC4997883 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.

Dang Uyen T UT Zamora Idalia I Hevener Kirk E KE Adhikari Sudip S Wu Xiaoqian X Hurdle Julian G JG

Antimicrobial agents and chemotherapy 20160822 9

We characterized clinically occurring and novel mutations in the β subunit of RNA polymerase in Clostridium difficile (CdRpoB), conferring rifamycin (including rifaximin) resistance. The Arg505Lys substitution did not impose an in vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of CdRpoB. In general, most mutations lacked in vitro fitness costs, suggesting that rifamycin r ...[more]

PMID: 27381389

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Project description:Study Design Retrospective database analysis. Objective The purpose of this study is to investigate incidence, comorbidities, and impact on health care resources of Clostridium difficile infection after cervical spine surgery. Methods A total of 1,602,130 cervical spine surgeries from the Nationwide Inpatient Sample database from 2002 to 2011 were included. Patients were included for study based on International Classification of Diseases Ninth Revision, Clinical Modification procedural codes for cervical spine surgery for degenerative spine diagnoses. Baseline patient characteristics were determined. Multivariable analyses assessed factors associated with increased incidence of C. difficile and risk of mortality. Results Incidence of C. difficile infection in postoperative cervical spine surgery hospitalizations is 0.08%, significantly increased since 2002 (p < 0.0001). The odds of postoperative C. difficile infection were significantly increased in patients with comorbidities such as congestive heart failure, renal failure, and perivascular disease. Circumferential cervical fusion (odds ratio [OR] = 2.93, p < 0.0001) increased the likelihood of developing C. difficile infection after degenerative cervical spine surgery. C. difficile infection after cervical spine surgery results in extended length of stay (p < 0.0001) and increased hospital costs (p < 0.0001). Mortality rate in patients who develop C. difficile after cervical spine surgery is nearly 8% versus 0.19% otherwise (p < 0.0001). Moreover, multivariate analysis revealed C. difficile to be a significant predictor of inpatient mortality (OR = 3.99, p < 0.0001). Conclusions C. difficile increases the risk of in-hospital mortality and costs approximately $6,830,695 per year to manage in patients undergoing elective cervical spine surgery. Patients with comorbidities such as renal failure or congestive heart failure have increased probability of developing infection after surgery. Accepted antibiotic guidelines in this population must be followed to decrease the risk of developing postoperative C. difficile colitis.

Dataset Information

Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.

Publications

Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.

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