Outcomes of health care-associated pneumonia empirically treated with guideline-concordant regimens versus community-acquired pneumonia guideline-concordant regimens for patients admitted to acute care wards from home.

BACKGROUND: The introduction of the health care-associated pneumonia (HCAP) categorization expanded recommendations for broad-spectrum empiric antibiotics to pneumonia patients presenting from the community with recent health care-system exposure. However, the efficacy of such regimens in improving clinical outcomes in these patients has not been well established. OBJECTIVE: To compare the clinical outcomes of HCAP patients treated initially with HCAP guideline-concordant antibiotic regimens to those treated initially with community-acquired pneumonia (CAP) guideline-concordant antibiotic regimens. METHODS: This retrospective study included HCAP patients presenting from home and admitted to general medical wards. HCAP regimen patients were treated empirically with at least 1 antipseudomonal agent. All other patients were assigned to the CAP regimen group. The primary end point was clinical cure at 30 days postdischarge. Subgroup analysis was performed in patients hospitalized 1-30 days and 31-90 days before the HCAP admission. RESULTS: Of 228 HCAP admissions, 122 patients received CAP regimens and 106 received HCAP regimens. The 2 groups were similar at baseline, including Pneumonia Severity Index scores. Attributable clinical cure occurred in 75.4% of CAP regimen patients and 69.8% of HCAP regimen patients (p = 0.34). Overall clinical cure occurred in 59.8% of CAP regimen patients and 54.7% of HCAP regimen patients (p = 0.44). The CAP regimen group used fewer days of intravenous antibiotics (4.39 vs 7.75, p < 0.0001) and had shorter lengths of stay (6.36 vs 8.58 days, p < 0.0001). For patients hospitalized 31-90 days earlier, clinical cure was higher in the CAP regimen group (attributable, 82.9% vs 60.0%, p = 0.0090; overall, 67.1% vs 47.5%, p = 0.044). CONCLUSIONS: Compared to CAP guideline-concordant regimens, treatment of HCAP with HCAP guideline-concordant regimens did not increase clinical cure rates and was associated with lower clinical cure rates in patients hospitalized 31-90 days prior to the HCAP admission. This study suggests that broad-spectrum empiric antibiotics may not be necessary in all HCAP patient groups.

Proteomic characterization of midproliferative and midsecretory human endometrium.

This study aimed to identify proteins differentially expressed in the human endometrium between the proliferative and secretory phases of normal menstrual cycles by 2D differential in-gel electrophoresis (DIGE). A total of 196 out of 1017 spots were differentially expressed (p < 0.05). Mass spectrometry identified 76 proteins representing 41 different gene products. Immunohistochemistry confirmed the observed changes in 3 representative proteins (Rho-GDIalpha, CLIC1, PGRMC1). Biological pathway analysis identified the Jnk and EGF signaling pathways as key regulators of protein expression in the midsecretory phase of endometrial proteome.

Open-tubular electrochromatographic characterization of synthetic peptides.

The open-tubular electrochromatographic (OT-CEC) migration behavior of a series of peptides, based on a common structural feature, has been characterized using two different types of chemically modified etched capillaries. The organic moieties immobilized onto the capillary inner surface were n-butylphenyl and cholesterol-10-undecenaoate, respectively. The structure-migration behavior of this set of peptides has been studied at several pH values and with methanol at different concentrations as an organic solvent modifier of the buffer electrolyte composition. By comparing the structural properties of the peptides, such as their amino acid sequences, charge-to-mass ratios and intrinsic hydrophobicities to their migrational behavior, the relative contribution of electrophoretic and chromatographic mobility to the overall migration times, elution order, and selectivity has been determined. Moreover, the experimental data provide important insight into procedures that can be used to modulate the separation of peptides in OT-CEC through variation of the composition of the electrolyte buffer as well as via the properties of the bonded organic moiety.

Open tubular capillary electrochromatography of synthetic peptides on etched chemically modified columns.

Two sets of peptides, each having structurally similar amino acid sequences, have been investigated by capillary electrochromatography (CEC) using etched chemically modified capillaries as the separation medium. In comparison to gradient RP-HPLC, the resolving power of the described CEC methods has been found to be superior. A number of variables have been examined with respect to optimization of the separation of these closely related peptides with several different etched chemically modified capillaries. These experimental variables included the nature of the bonded moiety, the pH, the organic modifier type, and the amount of organic modifier in the buffer electrolyte. Systematic variation of these parameters results in significant changes in the migrational behavior of the investigated peptides and provides important insight into the underlying molecular separation processes that prevail in open tubular CEC. Moreover, under optimized conditions, efficient separations characterized by highly symmetrical peaks were achieved. In addition, this study has permitted the long-term stability as well as the short-term and long-term reproducibility of the etched chemically modified capillaries to be documented.

Separation of structurally related synthetic peptides by capillary zone electrophoresis.

The separation of two different sets of synthetic peptides has been investigated by high-performance capillary zone electrophoresis utilising naked, fused silica capillaries. The effects of electrolyte pH, buffer concentration, capillary length and electric field strength on the separation efficiency and selectivity were systematically varied, with the highest resolution achieved with buffer electrolytes of low pH and relatively high ionic strength. Under optimised separation conditions utilising the "short end injection" separation approach with negative electric field polarity, a series of eight structurally-related synthetic peptides were baseline resolved within 4 min without addition of any modifier of the background electrolyte with separation efficiencies in the vicinity of 600000 theoretical plates/m. Further significant enhancement of separation efficiencies could be achieved by taking advantage of the "long end injection" approach with positive electric field polarity. The outcome of these experimental variations parallels the "sweeping" effect that has been observed in the capillary electrochromatographic and micellar electrokinetic separations of polar molecules and permits rapid resolution of peptides with focusing effects. In addition, small changes in the electrolyte buffer pH and concentration were found to have a significant impact on the selectivity of synthetic peptides of similar intrinsic charge. These observations indicate that multi-modal separation mechanisms operated under these conditions with the unmodified fused silica capillaries. This study, moreover, documents additional examples of peptide-specific multi-zoning behaviour in the high-performance capillary zone electrophoretic separation of synthetic peptides.