Impact of real time polymerase chain reaction technology on the therapeutic approach to treatment of staphylococcal infections

Can the early identification of the species of staphylococcus responsible for infection by the use of Real Time PCR technology influence the approach to the treatment of these infections? ^ This study was a retrospective cohort study in which two groups of patients were compared. The first group, ‘Physician Aware’ consisted of patients in whom physicians were informed of specific staphylococcal species and antibiotic sensitivity (using RT-PCR) at the time of notification of the gram stain. The second group, ‘Physician Unaware’ consisted of patients in whom treating physicians received the same information 24–72 hours later as a result of blood culture and antibiotic sensitivity determination. ^ The approach to treatment was compared between ‘Physician Aware’ and ‘Physician Unaware’ groups for three different microbiological diagnoses—namely MRSA, MSSA and no-SA (or coagulase negative Staphylococcus). ^ For a diagnosis of MRSA, the mean time interval to the initiation of Vancomycin therapy was 1.08 hours in the ‘Physician Aware’ group as compared to 5.84 hours in the ‘Physician Unaware’ group (p=0.34). ^ For a diagnosis of MSSA, the mean time interval to the initiation of specific anti-MSSA therapy with Nafcillin was 5.18 hours in the ‘Physician Aware’ group as compared to 49.8 hours in the ‘Physician Unaware’ group (p=0.007). Also, for the same diagnosis, the mean duration of empiric therapy in the ‘Physician Aware’ group was 19.68 hours as compared to 80.75 hours in the ‘Physician Unaware’ group (p=0.003) ^ For a diagnosis of no-SA or coagulase negative staphylococcus, the mean duration of empiric therapy was 35.65 hours in the ‘Physician Aware’ group as compared to 44.38 hours in the ‘Physician Unaware’ group (p=0.07). However, when treatment was considered a categorical variable and after exclusion of all cases where anti-MRS therapy was used for unrelated conditions, only 20 of 72 cases in the ‘Physician Aware’ group received treatment as compared to 48 of 106 cases in the ‘Physician Unaware’ group. ^ Conclusions. Earlier diagnosis of MRSA may not alter final treatment outcomes. However, earlier identification may lead to the earlier institution of measures to limit the spread of infection. The early diagnosis of MSSA infection, does lead to treatment with specific antibiotic therapy at an earlier stage of treatment. Also, the duration of empiric therapy is greatly reduced by early diagnosis. The early diagnosis of coagulase negative staphylococcal infection leads to a lower rate of unnecessary treatment for these infections as they are commonly considered contaminants. ^

The effect of v-{\it mos\/} expression on the regulation of the {\it fos\/} promoter in 490N3T cells

The v-mos oncogene acquired by Moloney murine sarcoma viruses by recombination with the c-mos proto-oncogene encodes a 37kD cytoplasmic serine/threonine protein kinase which can phosphorylate tubulin and vimentin, as well as the cyclin B component of the maturation promotion factor complex (MPF). Our earliest experiments asked whether the v-mos protein could activate the transcription of transin. Since the transcription of transin was known to be mediated by both fos-dependent and fos-independent pathways, it seemed possible that the induction of transin transcription by v-mos might be mediated by p55$\sp{\rm c-}\sp{fos}$. Surprisingly, when we examined the effect of v-mos on the fos promoter, we observed a significant inhibition of transcription in 49ON3T cells, a subclone of N1H3T3 mouse fibroblasts.^ In this thesis we show that in mouse 49ON3T cells, transcription from the fos promoter is up to 10-fold repressed in the presence of v-mos. Moreover, in this cell line several other transforming constructs (v-ras, v-src, neu) also cause repression of the fos promoter. Interestingly, nontransforming oncogenes (e.g. myc) do not repress fos transcription. The repressive effect was lost in v-mos mutants lacking in ATP-binding or kinase domain, arguing that the effect on fos transcription was mediated by v-mos transforming kinase activity. As mos is a cytoplasmic protein, it was assumed that transcriptional repression was mediated by conversion of a transcriptional regulator to a repressor by mos-induced phosphorylation. As a first approximation of the identity of this factor, we mapped the position of the mos effect on the fos promoter using reporter (CAT) constructs. We found that repression was mediated by regions $-$221 to $-$106 and $-$122 to $-$65 relative to the fos transcriptional start site, both of which regions regulate baseline fos transcription. There are direct repeats containing E2F transcriptional activator/repressor recognition motifs in these regions which bind similar nuclear proteins independently of v-mos presence or absence. Our data show that the contribution of the direct repeat to baseline fos transcription is mediated by these E2F sites with perhaps some contribution from the overlapping retinoblastoma control element (RCE). We have shown that there is a separate DNA protein interaction in the direct repeat which is more pronounced in the presence of v-mos. The recognition site for this protein, which we speculate mediates the mos-induced downregulation of fos transcription, overlaps but is distinct from the E2F and RCE binding sites. (Abstract shortened by UMI.) ^

The cost effective management of Central Line-Associated Bloodstream Infections (CLABSIs) comparing the central line bundle to antimicrobialcoated central venous catheters: A systematic review

Central Line-Associated Bloodstream Infections (CLABSIs) are one of the most costly and preventable cases of morbidity and mortality among intensive care units (ICUs) in health care today. In 2008, the Centers for Medicare and Medicaid Services Medicare Program, under the Deficit Reduction Act, announced it will no longer reimburse hospitals for such adverse events among those related to CLABSIs. This reveals the financial burden shift onto the hospital rather than the health care payer who can now withhold reimbursements. With this weighing more heavily on hospital management, decision makers will need to find a way to completely prevent cases of CLABSI or simply pay for the financial consequences. ^ To reduce the risk of CLABSIs, several clinical, preventive interventions have been studied and even instituted including the Central Line (CL) Bundle and Antimicrobial Coated Central Venous Catheters (AM-CVCs). I carried out a formal systematic review on the topic to compare the cost-effectiveness of the Central Line (CL) Bundle to the commercially available antimicrobial coated central venous catheters (AM-CVCs) in preventing CLABSIs among critically and chronically ill patients in the U.S. Evidence was assessed for inclusion against predefined criteria. I, myself, conducted the data extraction. Ten studies were included in the review. Efficacy in reducing the mean incidence rate of CLABSI by the CL Bundle and AM-CVC interventions were compared with one another including costs. ^ The AM-CVC impregnated with antibiotics, rifampin-minocycline (AI-RM) is more clinically effective than the CL Bundle in reducing the mean rate of CLABSI per 1,000 catheter days. The lowest mean incidence rate of CLABSI per 1,000 catheter days among the AM-CVC studies was as low as zero in favor of the AI-RM. Moreover, the review revealed that the AI-RM appears to be more cost-effective than the CL Bundle. Results showed the adjusted incremental cost of the CL Bundle per ICU patient requiring a CVC to be approximately $196 while the AI-RM at only an additional cost of $48 per ICU patient requiring a CVC. ^ Limited data regarding the cost of the CL Bundle made it difficult to make a true comparison to the direct cost of the AM-CVCs. However, using the result I did have from this review, I concluded that the AM-CVCs do appear to be more cost-effective in decreasing the mean rate of CLABSI while also minimizing incremental costs per CVC than the CL Bundle. This review calls for further research addressing the cost of the CL Bundle and compliance and more effective study designs such as randomized control trials comparing the efficacy and cost of the CL Bundle to the AM-CVCs. Barriers that may face health care managers when implementing the CL Bundle or AM-CVCs include additional costs associated with the intervention, educational training and ongoing reinforcement as well as creating a new culture of understanding.^

Assessing how middle school students' nutrient intake varies based on the availability of a la carte offerings at lunch

Purpose: School districts in the U.S. regularly offer foods that compete with the USDA reimbursable meal, known as `a la carte' foods. These foods must adhere to state nutritional regulations; however, the implementation of these regulations often differs across districts. The purpose of this study is to compare two methods of offering a la carte foods on student's lunch intake: 1) an extensive a la carte program in which schools have a separate area for a la carte food sales, that includes non-reimbursable entrees; and 2) a moderate a la carte program, which offers the sale of a la carte foods on the same serving line with reimbursable meals. ^ Methods: Direct observation was used to assess children's lunch consumption in six schools, across two districts in Central Texas (n=373 observations). Schools were matched on socioeconomic status. Data collectors were randomly assigned to students, and recorded foods obtained, foods consumed, source of food, gender, grade, and ethnicity. Observations were entered into a nutrient database program, FIAS Millennium Edition, to obtain nutritional information. Differences in energy and nutrient intake across lunch sources and districts were assessed using ANOVA and independent t-tests. A linear regression model was applied to control for potential confounders. ^ Results: Students at schools with extensive a la carte programs consumed significantly more calories, carbohydrates, total fat, saturated fat, calcium, and sodium compared to students in schools with moderate a la carte offerings (p<.05). Students in the extensive a la carte program consumed approximately 94 calories more than students in the moderate a la carte program. There was no significant difference in the energy consumption in students who consumed any amount of a la carte compared to students who consumed none. In both districts, students who consumed a la carte offerings were more likely to consume sugar-sweetened beverages, sweets, chips, and pizza compared to students who consumed no a la carte foods. ^ Conclusion: The amount, type and method of offering a la carte foods can significantly affect student dietary intake. This pilot study indicates that when a la carte foods are more available, students consume more calories. Findings underscore the need for further investigation on how availability of a la carte foods affects children's diets. Guidelines for school a la carte offerings should be maximized to encourage the consumption of healthful foods and appropriate energy intake.^