Antibiotic optimization. An evaluation of patient safety and economic outcomes

BACKGROUND: Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study. METHODS: Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database. RESULTS: Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11). CONCLUSIONS: This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense.     

Surface chemistry of wood‐based phosphoric acid‐activated carbons and its effects on adsorptivity

The surface oxygen content of selected wood‐based phosphoric acid‐activated carbons was quantified using X‐ray photoelectron spectroscopy (XPS) and correlated with the residual bulk phosphate levels of the carbons and their adsorptivity in solution. The adsorption of Al³⁺, Cu²⁺, and para‐chlorophenol, respectively, from water decreased as a function of increasing surface oxygen content of the carbons. When the carbon of lowest surface oxygen content was oxidized with ozone to impart a surface oxygen content comparable to that of a carbon with a much higher phosphate level, adsorption of Al³⁺, Cu²⁺, and para‐chlorophenol from water decreased proportionally. The increase in polarity of the carbon surface was accompanied by a decrease in pH and appeared to be the dominant factor with respect to the adsorption of the target species from water. Copyright © 2005 Society of Chemical Industry     

Graded comprehensive cardiopulmonary exercise testing in the evaluation of dyspnea unexplained by routine evaluation

The evaluation of dyspnea is problematic when a cause is inapparent after initial diagnostic studies. We examined the results and role of cardiopulmonary exercise testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1 and FVC. The CPET studies were interpreted by a panel and a consensus reached. Subsequent tests ordered by the primary physician were reviewed, and a final diagnosis was agreed on by the panel. Seven of 50 patients had cardiac limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either psychogenic dyspnea or no identifiable disease. Five patients had more than one clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a normal CPET had a higher VO2max and O2 pulse than those with cardiac disease, deconditioning, or hyperactive airways disease (HAD) (p < 0.05). Electrocardiographic changes identified cardiac disease while studies demonstrating ventilatory limitation identified a pulmonary process. In 24, deconditioning could not be distinguished from cardiac limitation. Of these, 14 responded to exercise training and/or weight loss, whereas 3 had cardiac disease, 7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable disease. We conclude that a diagnosis can be made in most patients with chronic dyspnea; however, further studies including bronchoprovocation are often required. Cardiopulmonary exercise testing is useful in identifying a cardiac or pulmonary process, but it is insensitive in distinguishing cardiac disease from deconditioning.     

Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells

There is little information concerning the intracellular function of inositol 1,3,4,5,6-pentakis- and hexakisphosphate, despite their being the most abundant inositol polyphosphates. Current opinions that they play passive roles as antioxidants (Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. (1987) J. Biol. Chem. 259, 3620-3624) or "housekeeping" molecules (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205) arises from belief in their metabolic lethargy. However, we have discovered that cell homogenates, incubated with 5 mM fluoride and 5 mM ATP, converted both inositol hexakisphosphate (Km = 2 +/- 0.5 microM, Vmax = 9 +/- 2 pmol/mg of protein/min) and inositol 1,3,4,5,6-pentakisphosphate (Km = 13 +/- 4 microM, Vmax = 11 +/- 5 pmol/mg of protein/min) to more polar products. These reactions were also observed in intact cells treated with 0.5-20 mM fluoride, and the precursor/product relationships were confirmed by comparing the effects of fluoride on cells differentially labeled with [3H]inositol in either short-term or pulse-chase protocols. The novel products were determined to be inositol pyrophosphates because of their relatively specific hydrolysis by tobacco pyrophosphatase and alkaline phosphatase. The pyrophosphates were metabolized rapidly by cell homogenates back to their pentakisphosphate and hexakisphosphate precursors. This endogenous pyrophosphatase activity was inhibited by up to 99% by 5 mM fluoride in vitro. In intact cells incubated with 10 mM fluoride, about 20% of the inositol 1,3,4,5,6-pentakisphosphate pool, and 50% of the inositol hexakisphosphate pool were each converted to pyrophosphate derivatives within 1 h.     

Genomic characterization of the coding region of the human type II 5''-deiodinase gene

The conserved residue Asp477 in yeast transketolase is located in the substrate channel of the enzyme and forms a hydrogen bond with the C2-hydroxyl group of the acceptor substrate. The significance of this interaction for the recognition of the preferred acceptor substrates, D-alpha-hydroxyaldehydes was investigated by site-directed mutagenesis. In the wild-type enzyme the kcat/KM values are by three to four orders of magnitude lower for 2-deoxyaldoses or substrates with L-configuration at the C2-atom. In the Asp477 Ala mutant, the kcat/KM values for D-alpha-hydroxyaldehydes are decreased by a thousandfold, while the kcat/KM values for substrates with L-configuration or 2-deoxyaldoses are similar to wild-type enzyme. These results indicate that Asp477 is involved in determining the enantioselectivity of transketolase.     

The rare metastasis of osteosarcoma of a long bone associated with von Recklinghausen''s neurofibromatosis

Benign mesothelioma of the pleura is a very rare tumor. The cells responsible originate from either the mesothelium or the submesothelium. This is why such tumors are described in the literature as fibroma of the pleura, mesothelial fibroma, localized fibrous mesothelioma and monophasic spindle cell tumor. Their growth, is very slow taking several years or even decades. In contrast to the more common malignant mesothelioma of the pleura, it is not related to asbestos exposure. This report deals with a 47-year-old woman patient with a giant benign mesothelioma of the pleura in the region of the right thorax, which was completely removed by thoracotomy.     

HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense

HAH1 is a 68-amino acid protein originally identified as a human homologue of Atx1p, a multi-copy suppressor of oxidative injury in sod1 delta yeast. Molecular modeling of HAH1 predicts a protein structure of two alpha-helices overlaying a four-stranded antiparallel beta-sheet with a potential metal binding site involving two conserved cysteine residues. Consistent with this model, in vitro studies with recombinant HAH1 directly demonstrated binding of Cu(I), and site-directed mutagenesis identified these cysteine residues as copper ligands. Expression of wild type and mutant HAH1 in atx1 delta yeast revealed the essential role of these cysteine residues in copper trafficking to the secretory compartment in vivo, as expression of a Cys-12/Cys-15 double mutant abrogated copper incorporation into the multicopper oxidase Fet3p. In contrast, mutation of the highly conserved lysine residues in the carboxyl terminus of HAH1 had no effect on copper trafficking to the secretory pathway but eliminated the antioxidant function of HAH1 in sod1 delta yeast. Taken together, these data support the concept of a unique copper coordination environment in HAH1 that permits this protein to function as an intracellular copper chaperone mediating distinct biological processes in eucaryotic cells.     

Primary gamma delta cell clones can be defined phenotypically and functionally as Th1/Th2 cells and illustrate the association of CD4 with Th2 differentiation

The division of CD4+ alpha beta T cells into Th1 and Th2 subsets has become an established and important paradigm. The respective activities of these subsets appear to have profound effects on the course of infectious and autoimmune diseases. It is believed that specific programs of differentiation induce the commitment of an uncommitted Th0 precursor cell to Th1 or Th2. A component of these programs is hypothesized to be the nature of MHC-peptide antigen presentation to the alpha beta T cell. It has heretofore remained uncertain whether a Th1/Th2 classification likewise defines, at the clonal level, gamma delta T cells. Such cells do not, as a general rule, express either CD4 or CD8 alpha beta, and they do not commonly recognize peptide-MHC. In this report, gamma delta cell clones are described that conform strikingly to the Th1/Th2 classification, both by cytokine expression and by functional activities of the clones in vitro and in vivo. Provocatively, both the gamma delta cell clones and primary gamma delta cells in vivo showed a strong association of the Th2 phenotype with CD4 expression. These results are discussed with regard to the immunoregulatory role that is increasingly emerging for gamma delta cells.     

Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion

BACKGROUND: Tissue subjected to a period of ischemia undergoes morphological and functional damage that increases during the reperfusion phase. The aim of the present work was to assess the possible improvement induced by exogenous administration of nitric oxide (NO) on renal injury and inflammatory reaction in an experimental animal model of renal ischemia-reperfusion (I-R). METHODS: Ischemia was achieved by ligation of the left arteria and vein for 60 min, followed first by contralateral nephrectomy and then reestablishment of blood flow. Molsidomine, used as an NO donor, was administered by systemic injection 30 min before reperfusion. The effect of molsidomine was compared with the effect of hydralazine, a non-NO donor hypotensive agent. RESULTS: Treatment with molsidomine improved the renal dysfunction (increase in plasma creatinine and urea levels) caused by I-R. Moreover, molsidomine blunted the enhanced production of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL] 1alpha), the increase in tissular levels of superoxide anions and oxygen free radical scavengers, and the neutrophilic infiltration observed in the ischemic kidney. One hundred percent survival was achieved in the group of animals treated with the NO donor, whereas the groups of animals undergoing I-R that did not receive molsidomine showed a 40% mortality from the second day after reperfusion. CONCLUSIONS: The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.