Secreted-protein response to sigmaU activity in Streptomyces coelicolor.

The filamentous bacterium Streptomyces coelicolor forms an aerial mycelium as a prerequisite to sporulation, which occurs in the aerial hyphae. Uncontrolled activity of the extracytoplasmic function sigma factor sigmaU blocks the process of aerial mycelium formation in this organism. Using a green fluorescent protein transcriptional reporter, we have demonstrated that sigU transcription is autoregulated. We have defined a sigmaU-dependent promoter sequence and used this to identify 22 likely sigmaU regulon members in the S. coelicolor genome. Since many of these genes encode probable secreted proteins, we characterized the extracellular proteome of a mutant with high sigmaU activity caused by disruption of rsuA, the presumed cognate anti-sigma factor of sigmaU. This mutant secreted a much greater quantity and diversity of proteins than the wild-type strain. Peptide mass fingerprinting was used to identify 79 proteins from the rsuA mutant culture supernatant. The most abundant species, SCO2217, SCO0930, and SCO2207, corresponded to secreted proteins or lipoproteins of unknown functions whose genes are in the proposed sigmaU regulon. Several unique proteases were also detected in the extracellular proteome of the mutant, and the levels of the protease inhibitor SCO0762 were much reduced compared to those of the wild type. Consequently, extracellular protease activity was elevated about fourfold in the rsuA mutant. The functions of the proteins secreted as a result of sigmaU activity may be important for combating cell envelope stress and modulating morphological differentiation in S. coelicolor.

Long-term central venous catheter use and risk of infection in older adults with cancer.

PURPOSE: Long-term central venous catheters (CVCs) are often used in patients with cancer to facilitate venous access to administer intravenous fluids and chemotherapy. CVCs can also be a source of bloodstream infections, although this risk is not well understood. We examined the impact of long-term CVC use on infection risk, independent of other risk factors such as chemotherapy, in a population-based cohort of patients with cancer. PATIENTS AND METHODS: We conducted a retrospective analysis using SEER-Medicare data for patients age > 65 years diagnosed from 2005 to 2007 with invasive colorectal, head and neck, lung, or pancreatic cancer, non-Hodgkin lymphoma, or invasive or noninvasive breast cancer. Cox proportional hazards regression was used to examine the relationship between CVC use and infections, with CVC exposure as a time-dependent predictor. We used multivariable analysis and propensity score methods to control for patient characteristics. RESULTS: CVC exposure was associated with a significantly elevated infection risk, adjusting for demographic and disease characteristics. For patients with pancreatic cancer, risk of infections during the exposure period was three-fold greater (adjusted hazard ratio [AHR], 2.93; 95% CI, 2.58 to 3.33); for those with breast cancer, it was six-fold greater (AHR, 6.19; 95% CI, 5.42 to 7.07). Findings were similar when we accounted for propensity to receive a CVC and limited the cohort to individuals at high risk of infections. CONCLUSION: Long-term CVC use was associated with an increased risk of infections for older adults with cancer. Careful assessment of the need for long-term CVCs and targeted strategies for reducing infections are critical to improving cancer care quality.

Central line-associated bloodstream infection surveillance outside the intensive care unit: a multicenter survey.

OBJECTIVE: The success of central line-associated bloodstream infection (CLABSI) prevention programs in intensive care units (ICUs) has led to the expansion of surveillance at many hospitals. We sought to compare non-ICU CLABSI (nCLABSI) rates with national reports and describe methods of surveillance at several participating US institutions. DESIGN AND SETTING: An electronic survey of several medical centers about infection surveillance practices and rate data for non-ICU patients. PARTICIPANTS: Ten tertiary care hospitals. METHODS: In March 2011, a survey was sent to 10 medical centers. The survey consisted of 12 questions regarding demographics and CLABSI surveillance methodology for non-ICU patients at each center. Participants were also asked to provide available rate and device utilization data. RESULTS: Hospitals ranged in size from 238 to 1,400 total beds (median, 815). All hospitals reported using Centers for Disease Control and Prevention (CDC) definitions. Denominators were collected by different means: counting patients with central lines every day (5 hospitals), indirectly estimating on the basis of electronic orders ([Formula: see text]), or another automated method ([Formula: see text]). Rates of nCLABSI ranged from 0.2 to 4.2 infections per 1,000 catheter-days (median, 2.5). The national rate reported by the CDC using 2009 data from the National Healthcare Surveillance Network was 1.14 infections per 1,000 catheter-days. CONCLUSIONS: Only 2 hospitals were below the pooled CLABSI rate for inpatient wards; all others exceeded this rate. Possible explanations include differences in average central line utilization or hospital size in the impact of certain clinical risk factors notably absent from the definition and in interpretation and reporting practices. Further investigation is necessary to determine whether the national benchmarks are low or whether the hospitals surveyed here represent a selection of outliers.