Impact of a rapid multiplex polymerase chain reaction blood culture identification technology on outcomes in patients with vancomycin-resistant Enterococcal bacteremia.

BACKGROUND: Early appropriate antibiotic selection is associated with favorable clinical outcomes. We evaluated the clinical impact of rapid detection of vancomycin-resistant Enterococcal bacteremia (VREB) by the FilmArray blood culture identification (BCID) panel coupled with antimicrobial stewardship program (ASP) interventions. METHODS: Hospitalized adult patients with VREB identified by conventional methods (CM) were compared to patients with VREB identified by BCID. Real time alerts of BCID results were provided to the ASP for intervention. Outcomes were compared between groups. RESULTS: Sixty-eight patients with VREB were included (CM, n = 45; BCID, n = 23). No significant differences in demographics, pre-existing conditions, or clinical characteristics were observed. Significant reductions were demonstrated between CM and BCID groups in median hours to organism identification (47.7 versus 18.2, p < 0.001), to identification of vancomycin resistance from time of culture positivity (50.1 versus 1.2, p < 0.001), and time to effective therapy (50.3 versus 20.8, p < 0.001). Differences between CM and BCID did not reach statistical significance for mortality (35.6% versus 26.1%), 30-day readmission rate (31.0% versus 17.6%), intensive care length of stay [LOS] (8.0 versus 7.0 days), post-culture LOS (14.6 versus 14.1 days) or median hospital costs per patient ($95,826 versus $53,195). CONCLUSIONS: In patients with VREB, rapid organism and resistance detection by the BCID panel with ASP intervention significantly reduced time to initiation of effective therapy by over 24 hours. Non-significant improvements in clinical outcomes were observed. Additional studies are needed to determine the full implications of BCID technology on patient outcome.

Impact of a Stewardship-Initiated Restriction on Empirical Use of Ciprofloxacin on Nonsusceptibility of Escherichia coli Urinary Isolates to Ciprofloxacin.

STUDY OBJECTIVE: To evaluate the impact of a stewardship-initiated restriction on empirical use of ciprofloxacin on the nonsusceptibility of Escherichia coli urinary isolates to ciprofloxacin over time while controlling for the use of other key antibiotics with gram-negative activity. DESIGN: Retrospective single-center study. SETTING: Large tertiary and quaternary care academic medical center. ISOLATES: Of 3714 E. coli urinary isolates. MEASUREMENTS AND MAIN RESULTS: The susceptibilities of the E. coli urinary isolates to ciprofloxacin, ceftriaxone, cefepime, piperacillin-tazobactam, meropenem, trimethoprim-sulfamethoxazole, and nitrofurantoin obtained over a 7-year period (January 1, 2006-December 31, 2012) from adult inpatients were evaluated for potential relationships with antibiotic use over time by using multiple variable regression analysis. After introduction of the restriction on empirical use of ciprofloxacin in the first quarter of 2011, ciprofloxacin use declined from 141.1-39.8 defined daily doses/1000 patient-days, and the percentage of E. coli isolates that were not susceptible to ciprofloxacin decreased from 41.5-32.8%. With all antibiotics evaluated included in the model, no apparent relationships were found between the percentage of E. coli isolates nonsusceptible to ciprofloxacin and antibiotic use. However, when nonsignificant variables were eliminated (p>0.20), ciprofloxacin use was found to be positively associated with the percentage of E. coli isolates nonsusceptible to ciprofloxacin (p=0.037), whereas ceftriaxone use was negatively associated (p=0.045). CONCLUSION: The restriction and subsequent reduction of ciprofloxacin use was found to have a positive effect on the susceptibility of E. coli urinary isolates to ciprofloxacin.

Unanticipated Multiplex PCR-Based Identification of Polymicrobial Blood Culture Resulting in Earlier Isolation, Determination of Susceptibilities, and Optimization of Clinical Care.

We describe a case of polymicrobial bloodstream infection with six organisms identified by multiplex PCR that was initially thought to be a monomicrobial infection. Early recognition of specific Gram-positive, Gram-negative, and fungal organisms and resistance elements allowed significantly more rapid optimization of therapy.

Necrotizing Soft Tissue Infection Occurring after Exposure to Mycobacterium marinum.

Cutaneous infections caused by Mycobacterium marinum have been attributed to aquarium or fish exposure after a break in the skin barrier. In most instances, the upper limbs and fingers account for a majority of the infection sites. While previous cases of necrotizing soft tissue infections related to M. marinum have been documented, the importance of our presenting case is to illustrate the aggressive nature of M. marinum resulting in a persistent necrotizing soft tissue infection of a finger that required multiple aggressive wound debridements, followed by an amputation of the affected extremity, in order to hasten recovery.

Organ donation video messaging: differential appeal, emotional valence, and behavioral intention.

Video narratives increasingly are used to draw the public's attention to the need for more registered organ donors. We assessed the differential impact of donation messaging videos on appeal, emotional valence, and organ donation intentions in 781 non-registered adults. Participants watched six videos (four personal narratives, one informational video without personal narrative, and one unrelated to donation) with or without sound (subtitled), randomly sequenced to minimize order effects. We assessed appeal, emotional valence, readiness to register as organ donors, and donation information-seeking behavior. Compared to other video types, one featuring a pediatric transplant recipient (with or without sound) showed more favorable appeal (p < 0.001), generated more positive emotional valence (p < 0.01), and had the most favorable impact on organ donor willingness (p < 0.001). Ninety-five (12%) participants clicked through to a donation website after viewing all six videos. Minority race (OR = 1.94, 95% CI = 1.20, 3.13, p = 0.006), positive change in organ donor readiness (OR = 0.26, 95% CI = 0.14, 0.48, p < 0.001), and total positive emotion (OR = 1.05, 95% CI = 1.03, 1.07, p < 0.001) were significant multivariable predictors of clicking through to the donation website. Brief, one-min videos can have a very dramatic and positive impact on willingness to consider donation and behavioral intentions to register as an organ donor.

Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial.

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m(2) completed week 24. TxB2 increased in the RAL versus PI/NNRTI arm (+0.09 versus -0.02; P = 0.06). Baseline PGI-M was lower in the RAL arm (P = 0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho = 0.45; P = 0.04) and TxB2 (rho = 0.44; P = 0.005) changes, with a trend seen for PGE-M (rho = 0.41; P = 0.07). In an adjusted model, age ≥ 50 years (N = 8) was associated with increased PGE-M (P = 0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥ 50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.

A case of Exophiala oligosperma successfully treated with voriconazole.

Exophiala oligosperma is an uncommon pathogen associated with human infections, predominantly in immunocompromised hosts. Case reports of clinical infections related to E. oligosperma have been limited to 6 prior publications, all of which have shown limited susceptibility to conventional antifungal therapies, including amphotericin B, itraconazole, and fluconazole. We describe the first case of an E. oligosperma induced soft-tissue infection successfully treated with a 3-month course of voriconazole without persisting lesions.

A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy.

Lipohypertrophy in HIV-infected patients is associated with metabolic abnormalities. Raltegravir (RAL) is not known to induce fat changes or severe metabolic perturbations. HIV-infected women with central adiposity and HIV-1 RNA less than 50 copies per milliliter on non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based antiretroviral therapy (ART) continued their nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open label RAL immediately or after 24 weeks. The primary end point was 24-week between-group change in computed tomography (CT)-quantified visceral adipose tissue (AT) volume. Fasting lipids, glucose, C-reactive protein (CRP), anthropometric measurements, and patient-reported quality of life assessments were also measured. Thirty-six subjects provided 80% power to detect a 10% between-group difference in visceral AT over 24 weeks. Thirty-seven of 39 enrolled subjects completed week 24. At entry, subjects were 75% black or Hispanic, and on 62% PI-based and 38% NNRTI-based regimens. The median age was 43 years, CD4 count 558 cells per microliter, and body mass index (BMI) 32 kg/m(2). After 24 weeks, no statistically significant changes in visceral or subcutaneous AT, anthropometrics, BMI, glucose, or CRP were observed. In subjects receiving RAL, significant improvements in total and LDL cholesterol (p=0.04), self-reported belly size (p=0.02) and composite body size (p=0.02) were observed. Body size changes correlated well with percent visceral AT change. No RAL-related adverse events occurred. Compared to continued PI or NNRTI, switch to RAL was associated with statistically significant 24-week improvements in total and LDL cholesterol but not AT volumes. Additional insights into AT and metabolic changes in women on RAL will be provided by 48-week follow-up of the immediate-switch arm.

Measures of small-fiber neuropathy in HIV infection.

INTRODUCTION: Noninvasive methods are needed to detect distal sensory polyneuropathy in HIV-infected persons on antiretroviral therapy (ART). METHODS: Quantitative sudomotor axon reflex test (QSART) and Utah Early Neuropathy Scale (UENS), small-fiber sensitive measures, were assessed in subjects with and without clinical neuropathy. Pain was assessed by visual analog scale (VAS). RESULTS: Twenty-two subjects had symptoms and signs of neuropathy, 19 had neither, and all were receiving ART. Median sweat volume (µL) was lower at all testing sites in those with neuropathy compared to those without (p<0.01 for all). UENS and VAS (mm) were higher in neuropathy subjects (p<0.05 for each). Lower sweat volume at all sites correlated with higher pin UENS subscore, total UENS, and VAS (p<0.05 for all). In multivariable analyses adjusting for age, CD4⁺ T cells, sex, and use of "d-drug" ART, QSART and UENS remained associated (p=0.003). CONCLUSION: QSART and UENS have not been previously studied in this patient population and may identify small-fiber neuropathy in HIV-infected, ART-treated persons.

Serum leptin level mediates the association of body composition and serum C-reactive protein in HIV-infected persons on antiretroviral therapy.

Higher body mass index (BMI) is associated with increased serum C-reactive protein (CRP) levels in HIV-infected individuals on antiretroviral therapy (ART), but the relationship of adipose tissue mass to systemic inflammation is not well described in this population. We hypothesized that serum adipokine levels (i.e., hormones produced by adipocytes) are a superior predictor of CRP compared to anthropometric or radiographic measures of body composition in patients on effective, stable ART. We evaluated the relationship of serum leptin, adiponectin, and resistin, BMI, and dual energy x-ray absorptiometry (DEXA) measurements with serum highly sensitive CRP (hsCRP) in a cross-sectional cohort of 106 predominantly virologically suppressed, HIV-infected adults on ART for ≥24 weeks using multivariable linear regression and formal criteria to assess statistical mediation. Median BMI, hsCRP, and leptin values were 25.2 kg/m(2), 3.0 mg/liter, and 3.8 ng/ml, respectively. BMI and DEXA limb fat, body fat, and trunk fat measurements were significantly associated with both serum leptin and hsCRP levels (all p≤0.02). Leptin was also associated with hsCRP (p<0.01). The regression coefficient for the effect of BMI or DEXA measurements on hsCRP was reduced, and the relationship was no longer statistically significant, after adjusting for leptin, indicating leptin functioned as a mediating variable within these relationships. Adiponectin and resistin levels did not demonstrate similar effects. Serum leptin was a superior predictor of hsCRP compared to BMI and DEXA body fat measurements, which may reflect alterations in body composition in treated HIV infection and the important contribution of adipose tissue to inflammation in this population.

Advantages and disadvantages of surgical therapy and optimal extent of thyroidectomy for the treatment of hyperthyroidism.

Surgery is excellent therapy for hyperthyroidism, with no mortality,and few complications or recurrences. It achieves euthyroidism rapidly and consistently, avoids long-term risks of radioactive iodine and antithyroid medications, provides tissue for histology,renders childbearing immediately possible, and allows absolute titration of thyroid hormone. Advancements such as preoperative preparation and intraoperative parathyroid hormone monitoring have decreased risks greatly and improved outcomes. Hartley-Dunhill procedure is the treatment of choice. Patients should be rendered euthyroid before operation to decrease thyroid vascularity, to improve surgical planes, and to prevent life threatening thyroid storm. Patients must be monitored carefully for hypocalcemia, a potentially serious complication. Patients will require lifelong thyroid hormone replacement. Radioactive iodine ablation should be considered for disease recurrence after surgery.

Synthesis and structure-activity relationships of benzophenone hydrazone derivatives with insecticidal activity.

A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis.

The phosphatidylinositol 3-kinase pathway selectively controls sIL-1RA not interleukin-1beta production in the septic leukocytes.

Microbial components such as bacterial endotoxin lipopolysaccharide (LPS) can trigger highly lethal septic shock. The cardinal features of septic leukocytes include the repressed production of inflammatory cytokines, such as interleukin-1 beta (IL-1beta), and elevated production of anti-inflammatory cytokines, such as secretory interleukin-1 receptor antagonist (sIL-1RA). Pro- and anti-inflammatory cytokine gene transcriptions are equally repressed in septic leukocytes due to disruption of the LPS signaling pathway at the level of interleukin-1 receptor-associated kinase. The selective elevation of sIL-1RA protein in septic blood is caused by efficient translation of residual sIL-1RA message. In this study, we report that the LPS-inducible phosphatidylinositol 3-kinase (PI3-kinase)-dependent signaling pathway contributes to the elevated translation of sIL-1RA in septic/LPS-adapted leukocytes. We also observe that this pathway is gene specific and does not affect the production of proinflammatory IL-1beta protein.