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We report a case of a 48-year-old man with purulent pericarditis by Streptococcus viridans, despite aggressive treatment with antibiotics and partial pericardiectomy was complicated by left ventricle pseudo-aneurysm resulting in a fatal outcome. The case highlights the course of complicated purulent pericarditis and the use of noninvasive imaging for assessing early signs of pseudoaneurysm and its typical progression.

In published studies, cohorts of patients with bacteremia due to vancomycin-resistant Enterococcus (VRE) have predominantly been infected with Enterococcus faecium . Little is known about the epidemiology and outcomes associated with bacteremia due to VR Enterococcus faecalis . A retrospective study of isolates obtained from January 2008 to October 2010 was conducted at Detroit Medical Center (DMC). Unique patients with blood cultures positive for VRE were reviewed. Outcomes were analyzed using logistic regression. During the study period, 105 cases of bacteremia due to VR E. faecalis and 197 cases of bacteremia due to VR E. faecium were identified. The mean age in the study cohort was 61.5 ± 15 years; 162 subjects (53.6%) were male. After controlling for a propensity score, bacteremia due to VR E. faecalis was associated with >2-fold-lower in-hospital mortality than bacteremia due to VR E. faecium . Interestingly, bacteremia due to VR E. faecalis was associated with longer hospital stay after VRE isolation, although total length of stay was similar for groups with VR E. faecalis and VR E. faecium . Bacteremia due to VR E. faecalis was associated with a >2-fold-lower risk for mortality than bacteremia due to VR E. faecium , possibly due to the availability of β-lactam therapeutics for treatment of VR E. faecalis .

Ertapenem is active against extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae organisms but inactive against Pseudomonas aeruginosa and Acinetobacter baumannii . Due to a lack of therapeutic data for ertapenem in the treatment of ESBL bloodstream infections (BSIs), group 2 carbapenems (e.g., imipenem or meropenem) are often preferred for treatment of ESBL-producing Enterobacteriaceae , although their antipseudomonal activity is unnecessary. From 2005 to 2010, 261 patients with ESBL BSIs were analyzed. Outcomes were equivalent between patients treated with ertapenem and those treated with group 2 carbapenems (mortality rates of 6% and 18%, respectively; P = 0.18).

Summary Background Group B Streptococcus (GBS) is a known causative pathogen of neonatal sepsis, but the epidemiology in non-pregnant adults is less studied. Methods Retrospective case–control and cohort analyses of risk factors and outcomes of GBS infections among non-pregnant adults were conducted at the Detroit Medical Center from January 2005 to May 2010. Uninfected controls were matched to cases in a 3:1 ratio. Data were obtained from charts and pharmacy records. Identification of the bacteria and antimicrobial susceptibility testing were determined by MicroScan. Cox regression was used for matched multivariate analyses. Results Thirty-two patients with GBS infections were identified and were matched and compared to 96 controls. Compared to controls, patients with GBS infection were significantly younger. Immunosuppression, attributable mainly to neutropenia and recent use of glucocorticoids, was an independent predictor for GBS infection (odds ratio 2.7, p =0.03). Nine (28%) of the patients with GBS infection had bacteriological failure despite the administration of appropriate antimicrobial therapy. Of the 10 patients with bloodstream infections (BSI), three had endocarditis and four had central nervous system (CNS) infections. During the study period the incidence of infections decreased, but the rates of resistance to erythromycin and clindamycin increased. Conclusions GBS, previously considered a genitourinary pathogen, has emerged as a non-nosocomial opportunistic pathogen causing BSI, endocarditis, and CNS infections. Immunosuppression, particularly transient immunosuppressed states, was an independent predictor for GBS BSI. Resistance rates to macrolides and clindamycin continue to increase, and should be closely monitored.

Linezolid is an important agent for the treatment of infections because of vancomycin-resistant Enterococcus (VRE). This study identified independent predictors for isolation of linezolid-resistant VRE (LZD-R-VRE) and analyzed outcomes associated with linezolid resistance. Immunosuppression, prior surgery, and previous exposure to β-lactam antibiotics were independent predictors for isolation of LZD-R-VRE but not for LZD-susceptible-VRE. Prior exposure to linezolid was not a predictor for isolation of LZD-R-VRE.

Objective.To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia.Design.Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011.Setting.Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center.Patients.All patients with monomicrobial gram-negative bacteremia during the study period.Intervention.Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009).Results.Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related mortality (OR, 0.24 [95% CI, 0.08-0.76]).Conclusions.Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.

Fosfomycin activity versus carbapenem-resistant Enterobacteriaceae and vancomycin-resistant Enterococcus , Detroit, 2008–10

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.

Background: Guidelines recommend that agents other than vancomycin be considered for some types of infection due to methicillin-resistant Staphylococcus aureus (MRSA) when the minimum inhibitory concentration (MIC) to vancomycin is 2 μg/mL or more. Alternative therapeutic options include daptomycin and linezolid, 2 relatively new and expensive drugs, and trimethoprim/sulfamethoxazole (TMP/SMX), an old and inexpensive agent. Objective: To compare the clinical efficacy and potential cost savings associated with use of TMP/SMX compared to linezolid and daptomycin. Methods: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adults (age >18 years) with infections due to MRSA with an MIC to vancomycin of 2 μg/mL were included if they received 2 or more doses of TMP/SMX and/or daptomycin and/or linezolid. Data were abstracted from patient charts and pharmacy records. Results: There were 328 patients included in the study cohort: 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of 2 or more of these agents. In univariate analysis, patients who received TMP/SMX alone had significantly better outcomes, including in-hospital (p = 0.003) and 90-day mortality (p < 0.001) compared to patients treated with daptomycin or linezolid. Patients receiving TMP/SMX were also younger (p < 0.001), had fewer comorbid conditions (p < 0.001), had less severe acute severity of illness (p < 0.001), and received appropriate therapy more rapidly (p = 0.001). In multivariate models the association between TMP/SMX treatment and mortality was no longer significant. Antimicrobial cost savings associated with using TMP/SMX averaged $2067.40 per patient. Conclusions: TMP/SMX monotherapy compared favorably to linezolid and daptomycin in terms of treatment efficacy and mortality. Use of TMP/SMX instead of linezolid or daptomycin could potentially significantly reduce antibiotic costs. TMP/SMX should be considered for the treatment of MRSA infection with MIC of 2 μg/mL to vancomycin.

The hospital environment is increasingly recognized as a reservoir for hospital-acquired pathogens. During a 44-month study period, a total of 1,103 basins from 88 hospitals in the United States and Canada were sampled. Overall, 62.2% of the basins (at least 1 basin at each hospital) were contaminated with commonly encountered hospital-acquired pathogens.

Introduction: Our previous work has shown that the loss of Rab25 occurs in estrogen receptor (ER) and progesterone receptor (PR) negative breast cancer cell lines and human tumor samples and seems to correlate with an active ras pathway. We have expressed Rab25 in several hormonally insensitive breast cancer cell lines and have demonstrated marked reduction in tumor growth. Histologically, the tumor cells appear smaller, and angiogenesis is significantly reduced. We have investigated the mechanism by which Rab25 exerts its anti-tumorigenic effect. Loss of Rab25 cooperates with mutant Ras to promote tumorigenesis in primary human mammary epithelial cells (HMEC). HIF1-alpha levels are markedly increased with loss of Rab25 if Ras is overexpressed. Rab25 is expressed in both luminal and basal mammary epithelium at similar levels. The loss of rab25 enhances VEGF-A secretion and VEGFR1 expression. Monoclonal antibodies can be potentially used to target these pathways which appear to be active in Rab25 negative tumors. Materials and Methods: Cell culture - MDA-MB-231 cells were grown in DME medium with 10% FBS, and Rao-3 cell line and HMEC were grown in DFCI-1 medium. Cells were transduced with retroviral supernatant and selected. Expression of RAB25 in transduced cells was determined by RT-PCR and western blot. Silencing of Rab25-Rab-25 was silenced in RAO-2 cells by pENTRTM/H1/TO siRNA system (Invitrogen, Carlsbad, CA). Our shRNA sequences are designed using the BLOCK-iTTM RNAi Designer. The most effective silencer of Rab25 was selected on the basis of testing 3 sequence pairs. The double-stranded oligos were inserted into the pENTR/H1/TO vector and transfected into cells. Silencing of Rab25 in transduced cells was confirmed by RT-PCR and Western blot. qPCR analysis- Expression of HIF1-alpha was quantified using real-time PCR with fluorescence detection. Western blot- Western blot was performed on cell extracts for rab25 and ras. Immunohistochemistry - CK5/6 served as a basal maker, and CK18 served as a luminal maker for co-staining with Rab25 in human mammary gland. In vivo tumor formation assay − 5 × 106 cells in 0.1 ml PBS were injected into the left mammary fat pad of five week-old female nude mice. Mice were monitored for the following 7 weeks for tumor volume. Therapeutic assays- Cell lines were incubated with anti-VEGF-A, anti-VEGFR1, or both, and cell numbers were tabulated over 5 days. Results: 1) Rab25 loss cooperated with Ras to promote tumorigenesis in several donors. 2) HIF1α levels rose significantly with loss of Rab25 and Ras co-expression. 3) Rab25 is expressed in both basal and luminal normal mammary epithelium. 4) Both anti-VEGF-A and anti-VEGFR1 antibodies have therapeutic implications for Rab25 negative breast cancer cell lines. Conclusions: Rab25 is a tumor suppressor that antagonizes Ras and may be part of an important therapeutic pathway. Its loss may serve as therapeutic marker for certain types of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3073.