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Carlene A Muto

Publications and source records attributed to Carlene A Muto.

12 recordsLinked to original sources
PubMed2006

tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile.

Severe Clostridium difficile associated disease is associated with outbreaks of the recently described BI/NAP1 epidemic clone. This clone is characterized by an 18-bp deletion in the tcdC gene and increased production of toxins A and B in vitro. TcdC is a putative negative regulator of toxin A&B production. We characterized tcdC genotypes from a collection of C. difficile isolates from a hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone. Sequence analysis of tcdC was performed on DNA samples isolated from 199 toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously described 18- or 39-bp deletions. The remaining isolates comprised 15 unique genotypes. Of these, 5 genotypes contain 18- or 36-bp deletions. Of these five genotypes, one is characterized by a single nucleotide deletion at position 117 resulting in a frameshift that introduces a stop codon at position 196, truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates in this collection comprising the epidemic clone are characterized by this genotype. This result suggests that severe truncation of TcdC is responsible for the increased toxin production observed in strains belonging to the BI/NAP1 clone and that the 18-bp deletion is probably irrelevant to TcdC function. Further investigations are required to determine the effect of this and other tcdC genotypes on toxin production and clinical disease.

Amino Acid Sequence↗
PubMed2006

Multilocus variable-number tandem-repeat analysis for investigation of Clostridium difficile transmission in Hospitals.

Clostridium difficile is a major cause of antibiotic-associated gastrointestinal illness. Recently, an increased incidence of hospital-acquired infections with severe outcomes has been reported in North America and Europe. Current molecular-typing methods for detection of outbreaks and nosocomial transmission are labor-intensive, subjective, or insufficiently discriminatory to differentiate between closely related strains. This report describes the development of multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for molecular subtyping of C. difficile. Seven VNTR loci were identified from the C. difficile 630 genome by screening an isolate collection of various restriction endonuclease analysis (REA) types. The stability of the loci for short-term epidemiologic investigations was determined by performing MLVA on consecutive isolates of the same REA type from individual patients collected over as many as 90 days. Validation of MLVA for molecular genotyping was performed by direct comparison with REA results obtained from Hines Veterans Affairs Hospital on a combined collection of 40 C. difficile isolates from two different sources. The ability of MLVA to detect outbreaks was demonstrated on a collection of tertiary-care hospital isolates from a defined C. difficile outbreak in 2001. MLVA successfully clustered C. difficile isolates of the same REA type and discriminated isolates of unique REA type. Thus, MLVA is an objective, portable genotyping method that permits reliable detection of C. difficile outbreaks and can aid epidemiologic investigations of nosocomial transmission.

Bacterial Typing Techniques↗
PubMed2005

A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use.

BACKGROUND AND OBJECTIVE: Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. METHODS: A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. RESULTS: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. CONCLUSIONS: Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

Anti-Bacterial Agents↗
PubMed2003

SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus.

BACKGROUND: Infection control programs were created three decades ago to control antibiotic-resistant healthcare-associated infections, but there has been little evidence of control in most facilities. After long, steady increases of MRSA and VRE infections in NNIS System hospitals, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors made reducing antibiotic-resistant infections a strategic SHEA goal in January 2000. After 2 more years without improvement, a SHEA task force was appointed to draft this evidence-based guideline on preventing nosocomial transmission of such pathogens, focusing on the two considered most out of control: MRSA and VRE. METHODS: Medline searches were conducted spanning 1966 to 2002. Pertinent abstracts of unpublished studies providing sufficient data were included. RESULTS: Frequent antibiotic therapy in healthcare settings provides a selective advantage for resistant flora, but patients with MRSA or VRE usually acquire it via spread. The CDC has long-recommended contact precautions for patients colonized or infected with such pathogens. Most facilities have required this as policy, but have not actively identified colonized patients with surveillance cultures, leaving most colonized patients undetected and unisolated. Many studies have shown control of endemic and/or epidemic MRSA and VRE infections using surveillance cultures and contact precautions, demonstrating consistency of evidence, high strength of association, reversibility, a dose gradient, and specificity for control with this approach. Adjunctive control measures are also discussed. CONCLUSION: Active surveillance cultures are essential to identify the reservoir for spread of MRSA and VRE infections and make control possible using the CDC's long-recommended contact precautions.

Anti-Bacterial Agents↗
PubMed2002

Cost-effectiveness of perirectal surveillance cultures for controlling vancomycin-resistant Enterococcus.

BACKGROUND: Several hospitals opting not to use active surveillance cultures to identify carriers of vancomycin-resistant Enterococcus (VRE) have reported that adoption of other parts of the Centers for Disease Control and Prevention guideline for controlling VRE has had little to no impact. Because use of surveillance cultures and contact isolation controlled a large outbreak at this hospital, their costs were estimated for comparison with the excess costs of VRE bacteremias occurring at a higher rate at a hospital not employing these measures. SETTING: Two university hospitals. METHODS: Inpatients deemed high risk for VRE acquisition at this hospital underwent weekly perirectal surveillance cultures. Estimated costs of cultures and resulting isolation during a 2-year period were compared with the estimated excess costs of more frequent VRE bacteremias at another hospital of similar size and complexity not using surveillance cultures to control spread throughout the hospital. RESULTS: Of 54,052 patients admitted, 10,400 had perirectal swabs taken. Cultures and isolation cost an estimated $253,099. VRE culture positivity was limited to 193 (0.38%) and VRE bacteremia to 1 (0.002%) as compared with 29 bacteremias at the comparison hospital. The estimated attributable cost of VRE bacteremia at the comparison hospital of $761,320 exceeded the cost of the control program at this hospital by threefold. CONCLUSIONS: The excess costs of VRE bacteremia may justify the costs of preventive measures. The costs of VRE infections at other body sites, of deaths from untreatable infections, and of dissemination of genes for vancomycin resistance also help to justify the costs of implementing an effective control program.

Cell Culture Techniques↗
PubMedDate not supplied

Pittsburgh Regional Healthcare Initiative: a systems approach for achieving perfect patient care.

The Pittsburgh Regional Healthcare Initiative (PRHI) is an innovative model for health system change based on regionwide shared learning. By linking patient outcomes data with processes of care and sharing that information widely, PRHI supports measurable improvements in regionwide clinical practice and patient safety. In addition, through the redesign of problem solving at the front lines of care, PRHI helps health care organizations to evolve toward becoming sustainable systems of perfect patient care. This paper describes PRHI's design for change, reviews the progress and limitations of the shared learning model, and offers a set of broader policy considerations.

Humans↗