Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) in brain and spinal cord injury patients: potential for prolonged colonization.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To determine the prevalence of brain and spinal cord injury (BSCI) patients among all patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) and to evaluate clinical characteristics and duration of colonization. SETTING: Tertiary care academic medical center. METHODS: Electronic medical records of BSCI patients with KPC-KP from February 2009 to December 2014 were reviewed to determine clinical characteristics. Patients with multiple KPC-KPs were defined as those with isolates in different calendar months, and patients with a single positive isolate were compared with those with repeatedly positive isolates. Variables with a P-value of ⩽0.05 were considered statistically significant. Two archived isolates recovered from separate cultures of the same patient were compared with pulsed-field gel electrophoresis to calculate the duration of colonization. RESULTS: Of the 218 patients with KPC-KP, 86 (39%) had BSCI and 27 (31%) had multiple KPC-KPs. The KPC-KPs from 20 (74%) patients with multiple isolates were available for analysis. Patients with repeated positive isolates were more likely to be younger (P=0.05), African American (P=0.05), suffer gunshot injuries (P=0.01) and other trauma (P=0.03) and have decubitus ulcers (P=0.05). Of the 20 patients with multiple isolates for analysis, 13 (65%) patients were colonized with the same strain type over time, and the strain persisted on average 373 days. CONCLUSION: BSCI patients comprise a significant percentage of our KPC-KP population. Owing to repeated hospitalizations and prolonged colonization, they represent a substantial reservoir for these multidrug-resistant pathogens.

Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae among high-risk patients and rates of subsequent bacteremia.

BACKGROUND: Bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have been associated with increased hospital costs, length of stay, and patient mortality. However, the role of routine inpatient surveillance for ESBL colonization in predicting related infection is unclear. METHODS: From 2000 through 2005, we screened 17,872 patients hospitalized in designated high-risk units for rectal colonization with vancomycin-resistant enterococci and ESBL-producing Enterobacteriaceae using a selective culture medium. In patients with a bloodstream infection due to ESBL-producing Enterobacteriaceae (ESBL-BI) during the study period, surveillance results were evaluated for evidence of antecedent ESBL-producing Enterobacteriaceae colonization. RESULTS: The rate of ESBL-producing Enterobacteriaceae colonization doubled during the 6-year study period, increasing from 1.33% of high-risk patients in 2000 to 3.21% in 2005. Among patients with ESBL-producing Enterobacteriaceae colonization, 49.6% also carried vancomycin-resistant enterococci. The number of ESBL-BIs increased >4-fold in 5 years, from 9 cases in 2001 to 40 cases in 2005. Of 413 patients colonized with ESBL-producing Enterobacteriaceae, 35 (8.5%) developed a subsequent ESBL-BI. Of concern, more than one-half of all ESBL-BIs occurred in patients who were not screened. These 56 patients received a diagnosis of ESBL-BI in the emergency department, when hospitalized in low-risk medical units, or at transfer from an acute or long-term health care facility. CONCLUSIONS: Colonization with ESBL-producing Enterobacteriaceae is increasing at a rapid rate, and routine rectal surveillance for ESBL-producing Enterobacteriaceae may have clinical implications. However, in our experience, over one-half of patients with an ESBL-BI did not undergo screening through our current surveillance measures. As a result, targeted screening for ESBL-producing Enterobacteriaceae among additional patient populations may be integral to future ESBL-BI prevention and management efforts.

Pheromone-regulated genes required for yeast mating differentiation.

Yeast cells mate by an inducible pathway that involves agglutination, mating projection formation, cell fusion, and nuclear fusion. To obtain insight into the mating differentiation of Saccharomyces cerevisiae, we carried out a large-scale transposon tagging screen to identify genes whose expression is regulated by mating pheromone. 91,200 transformants containing random lacZ insertions were screened for beta-galactosidase (beta-gal) expression in the presence and absence of alpha factor, and 189 strains containing pheromone-regulated lacZ insertions were identified. Transposon insertion alleles corresponding to 20 genes that are novel or had not previously been known to be pheromone regulated were examined for effects on the mating process. Mutations in four novel genes, FIG1, FIG2, KAR5/ FIG3, and FIG4 were found to cause mating defects. Three of the proteins encoded by these genes, Fig1p, Fig2p, and Fig4p, are dispensible for cell polarization in uniform concentrations of mating pheromone, but are required for normal cell polarization in mating mixtures, conditions that involve cell-cell communication. Fig1p and Fig2p are also important for cell fusion and conjugation bridge shape, respectively. The fourth protein, Kar5p/Fig3p, is required for nuclear fusion. Fig1p and Fig2p are likely to act at the cell surface as Fig1:: beta-gal and Fig2::beta-gal fusion proteins localize to the periphery of mating cells. Fig4p is a member of a family of eukaryotic proteins that contain a domain homologous to the yeast Sac1p. Our results indicate that a variety of novel genes are expressed specifically during mating differentiation to mediate proper cell morphogenesis, cell fusion, and other steps of the mating process.