Ralph Corey

Duke University Medical Center, Durham, North Carolina, United States

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Publications (20)38.9 Total impact

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    ABSTRACT: Background: ORI is a lipoglycopeptide with rapid bactericidal activity against gram-positive bacteria including MRSA. Its concentration-dependent activity and long half- life allow for single dose administration. Methods: SOLO I and SOLO II were identical Phase 3, multicenter, double-blind, randomized studies. Adults with ABSSSI requiring IV therapy received either a single 1200 mg IV dose of ORI, or VAN for 7 to 10 days (1 g or 15mg/kg BID). Three efficacy endpoints were tested for non-inferiority: 1) primary composite end point at 48 to 72 h (cessation of spreading or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic); 2) investigator-assessed clinical cure 7 to 14 days after end of treatment; and 3) ≥20% reduction in lesion area at 48 to 72 h. Safety was measured to Day 60. Results: All pre-specified endpoints met the 10% non-inferiority margin in SOLO I and II. In the combined studies, 978 and 981 patients comprised the modified intent to treat (mITT) population for ORI and VAN, respectively. For the combined studies, efficacy outcomes were as follows: primary composite end point: ORI, 81.2%; VAN, 80.9%; investigator-assessed clinical cure: ORI, 81.2%; VAN, 80.2%; proportion of patients attaining ≥20% reduction in lesion area: ORI, 86.4%; VAN, 84.1% (Table). More MRSA patients treated with ORI attained > 20% reduction in lesion size compared to VAN (ORI 93.1%, VAN 87.1%; difference 6.1%; p = 0.032). Overall, safety profiles were similar: 55.3% of ORI patients and 56.9% of VAN patients reported at least one adverse event. Conclusion: A single 1200 mg dose of ORI was non-inferior to 7 to 10 days of VAN in treating ABSSSI caused by gram-positive pathogens. In summary ORI provides a single-dose alternative to multi-dose VAN for the treatment of ABSSSI. Efficacy outcomes in the SOLO trials (n [%]) Timepoint Endpoint ORI (n = 978) VAN (n = 981) ECE Cessation of spread, absence of fever, no rescue antibiotics 794 (81.2%) 794 (80.9%) ≥20% reduction of lesion area 845 (86.4%) 825 (84.1%) PTE Investigator-assessed clinical cure 794 (81.2%) 787 (80.2%)
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Oritavancin (ORI) is a lipoglycopeptide antibiotic characterized by rapid, concentration dependent bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), and by a long terminal half-life (245 hours) which allows for single dose treatment. The objective of this analysis is to evaluate the time to onset and duration of adverse events (AEs) in two phase 3 studies (SOLO I and II) in patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI). Methods: The SOLO studies were global, multi-center, randomized, double-blind studies with identical design evaluating single dose IV ORI (1200 mg) vs IV vancomycin(VAN, 1 g or 15 mg/kg, every 12 hours for 7 to 10 days) in adults with ABSSSI. Safety assessments included vital signs, ECG, safety laboratory analysis and occurrence of AEs and serious AEs (SAEs). An extended safety follow up assessment was conducted at Day 60 (+ 7days). Results: A total of 976 and 983 patients received ORI and VAN, respectively. The overall incidences of AE, SAE and AE leading to study drug discontinuation were similar between ORI (55.3%, 5.8% and 3.7%) and VAN (56.9%, 5.9% and 4.2%) treatments. Median time to onset and durations of AEs in both groups were the same (2 days and 3 days, respectively). The majority of AEs occurred within the first three days of the study (64.8% in ORI, 66.2% in VAN). The incidences of AE onset and AE duration by time intervals as outlined in Figures 1 and 2 were similar between treatment groups. Conclusion: The long terminal half-life of ORI does not prolong time to onset or duration of AEs. Single IV dose of 1200 mg ORI was well tolerated in ABSSSI patients. Figure 1: Time to Onset of Adverse Events by Time Interval Figure 2: Duration of Adverse Events by Time Interval
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 1500 mg b.i.d. with that of linezolid 600 mg b.i.d. in patients with suspected gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with ≥20% decrease in lesion area from baseline at 48 and 72 hours after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly nausea, vomiting, diarrhea, and headache. Adverse events (86% vs 74%) and withdrawals (28% vs 11%) were more frequent in the GSK1322322 group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from baseline in the lesion area in 73% (36/49) and 92% (24/26) of patients, respectively, at the 48-hour assessment and in 96% (44/46) and 100% (25/25) of patients, respectively, at the 72-hour assessment. Reductions in exudate/pus, pain, and skin infection score were comparable between GSK1322322 and linezolid treatment. Clinical success rates within the intent-to-treat population and the per-protocol population that completed the study were 67% and 91%, respectively, in the GSK1322322 group and 89% and 100%, respectively, in the linezolid group. These results will be used to guide dose selection of future studies with GSK1322322 to optimize the tolerability and efficacy in patients with ABSSSI. (http://www.clinicaltrials.gov, NCT01209078; http://www.gsk-clinicalstudyregister.com, PDF113414).
    Antimicrobial Agents and Chemotherapy 08/2014; · 4.57 Impact Factor
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    ABSTRACT: BACKGROUND. The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens.METHODS. Prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (Cohort A) to those treated with standard-of-care (SOC) antibiotics (Cohort B). Primary outcome was in-hospital mortality. Time-to-clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed.RESULTS. There were 29 and 149 patients included in Cohort A and Cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In Cohort A, median time-to-clearance of MRSA bacteremia was 1.0 d, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance as compared to SOC (1.0 vs. 5.0 d; p <0.01). Higher daptomycin dose-regimens were not associated with increased incidence of AEs.CONCLUSIONS. Higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens.
    Antimicrobial Agents and Chemotherapy 09/2013; · 4.57 Impact Factor
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    ABSTRACT: Background: S. aureus causes serious infections following cardiothoracic (CT) surgery. V710 is a novel vaccine containing the conserved S. aureus iron surface determinant B (IsdB) and was immunogenic & generally well-tolerated in volunteers. We studied preoperative vaccination to prevent serious S. aureus infections after CT surgery. Methods: In a blinded, randomized, event-driven Phase 2b/3 study, eligible adult patients scheduled for median sternotomy within 14-60 days of entry received a single 0.5-mL injection of V710 (60 μg) or placebo. The primary efficacy outcome was prevention of S. aureus bacteremia & deep sternal wound infection (including mediastinitis) through postoperative Day 90. Death, S. aureus-associated, & vaccine-related serious adverse events were monitored for the duration of the study. Results: An independent monitoring committee recommended study termination after the 2nd planned interim analysis due to safety concerns & low efficacy. Anti-IsdB IgG titers at the time of surgery in V710 recipients were consistently higher than prevaccination baseline levels & significantly higher than in placebo recipients. In V710 recipients, the geometric mean fold-rise [95% CI] in antibody titer with opsonophagocytic activity from baseline was 2.5 [2.2, 2.8] just prior to surgery & 1.9 [1.6, 2.2] on postoperative Day 90. However, V710 was not more efficacious than placebo in preventing primary endpoints (22 in 3528 V710 recipients vs 27 in 3517 placebo recipients; p = 0.584). Rates of vaccine-related serious adverse events (1 in each group) & all-cause mortality (5.7 vs 5.0 deaths per 100 person-yrs; p = 0.200) were not statistically different between groups, but V710 was associated with a higher rate of postoperative multi-organ failure than placebo (0.9 vs 0.5 events per 100 person-yrs; p=0.042). Mortality rates in patients who developed S. aureus infections were higher among V710 than placebo recipients (24.4 vs 4.2 per 100 person-yrs; D [95% CI] = 20.2 [9.2, 35.7]). Conclusion: Despite eliciting opsonophagocytic antibody, preoperative administration of V710 did not reduce serious S. aureus infections after CT surgery. Postoperative multi-organ failure occurred more often in V710 than placebo recipients. Higher mortality was observed among S. aureus-infected V710 recipients than S. aureus-infected placebo recipients.
    IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
  • Shein-Chung Chow, Ralph Corey, Min Lin
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    ABSTRACT: In clinical trials, an independent data monitoring committee (DMC) is often established to perform both ongoing safety data monitoring and interim efficacy analysis. These evaluations are performed in a blinded fashion in order to avoid possible operational biases that may be introduced to the trial after the review of the data. The DMCs for clinical trials using adaptive design methods are also positioned to implement the adaptation decision according to the prospective adaptation algorithm. While the DMC plays an important role in maintaining the validity and integrity of the intended clinical trial, adaptive design clinical trials trigger a greater role and increased responsibility for the DMC. To assist the sponsor in establishing a DMC, the U.S. Food and Drug Administration (FDA) published a draft guidance entitled Establishment and Operation of Clinical Trial Data Monitoring Committees in 2006. In this article, the composition, role/responsibility, and function/activity of a DMC are described. Concerns of the additional responsibilities of the DMC for adaptive design clinical trials are addressed. Although the intention of the DMC is well-intentioned, controversial issues inevitably occur. These controversial issues include, but are not limited to, (1) the challenge of the independence of a DMC and (2) the issue regarding the direct communication between the DMC and the FDA. Discussion of controversial issues and practical issues are also provided.
    Journal of Biopharmaceutical Statistics 07/2012; 22(4):853-67. · 0.73 Impact Factor
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    Shein-Chung Chow, Ralph Corey
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    ABSTRACT: In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.
    Orphanet Journal of Rare Diseases 11/2011; 6:79. · 4.32 Impact Factor
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    ABSTRACT: Oral viridians group streptococci (OVGS) have been implicated in infective endocarditis (IE) resulting in antibiotic prophylaxis (AP) prior to invasive dental procedures becoming the standard of care for preventing IE worldwide. However, in a review the UK National Institute for Health and Clinical Excellence (NICE) found a lack of scientific evidence for efficacy of AP and recommended it's cessation in March 2008. Objectives: The aim of this study was to assess compliance with the NICE guidelines and to identify any resulting increase in IE cases or deaths. Methods: National inpatient hospital activity data for patients discharged from hospitals in England with a diagnosis of IE were obtained and analysed along with AP prescribing data for England from January 2000 to October 2009. Results: Dentists were responsible for 92% of AP prescriptions using 3g amoxicillin or 600mg clindamycin. After the NICE guidelines, AP prescribing dropped 78% (p<0.0001) from 10,9001006 (meanSD) per month to 2417 in October 2009 or a mean of 3,4961564. Although there was an upward trend in IE cases and deaths from 2000-2009 it's slope did not increase in the 18 months following the NICE guidelines and using a pre-specified non-inferiority statistical test we were unable to demonstrate a significant increase in IE cases, IE deaths, or IE cases with a possible OVGS origin after NICE. We continue to monitor the data. Conclusions: A significant decrease in AP prescribing in the UK has not resulted in a detectable increase in IE cases or deaths. Thus the benefits of continuing AP in other parts of the world may need to be re-evaluated. These findings also support evidence that the risk of IE causing bacteraemia due to dental procedures may be small compared to the transient bacteraemias associated with mastication and oral hygiene procedures, particularly in those with poor oral hygiene.
    IADR General Session 2010; 07/2010
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    ABSTRACT: In a recent randomized trial of Staphylococcus aureus bacteremia and native valve endocarditis, daptomycin was found not inferior to standard therapy. We summarized findings in the subgroup of patients with endocarditis according to the Duke criteria. Patients were randomly assigned to receive daptomycin 6 mg/kg/day or standard therapy (vancomycin 1g every 12h or antistaphylococcal penicillin 2g every 4h, both with gentamicin 1mg/kg every 8h for the first 4 days). The primary end point was success in the modified intent-to-treat population 6 weeks after the end of therapy. Fifty-three patients were included: 35 with right-sided endocarditis (RIE) and 18 with left-sided endocarditis (LIE). The success rates in patients with RIE were similar between daptomycin and the comparator (42% vs 44%). Patients with RIE with septic pulmonary infarcts responded similarly to treatment with daptomycin and standard therapy (60% vs 67%). In the LIE population, treatment success rates were poor in both arms (11% vs 22%). Daptomycin is an efficacious and well-tolerated alternative to standard therapy in the treatment of RIE. Patients with LIE had a poor outcome regardless of the treatment received. Daptomycin is also effective in treating endocarditis with septic pulmonary infarcts.
    Enfermedades Infecciosas y Microbiología Clínica 02/2010; 28(8):498-503. · 1.48 Impact Factor
  • International Journal of Antimicrobial Agents 06/2009; 33. · 4.42 Impact Factor
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2009; 33.
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    ABSTRACT: Background: Mortality of SA NVIE is high. Although EVS, surgery performed during antibiotic treatment, is thought to improve the prognosis of IE, rates of EVS are lower in SA NVIE than in other groups. This study sought to find explanations for this paradox. Methods: Of the 3,284 cases of IE that had been enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study by 2007, we extracted 1,502 cases of Duke definite left-sided NVIE that occurred in non-IDUs. These included 392 cases of SA IE and 1,110 cases of IE due to other pathogens (non-SA NVIE). Two-group comparisons and adjusted survival analysis were performed. Results: Compared to non-SA NVIE, SA NVIE occurred more frequently in older subjects (p = 0.01). It was less often community-acquired (p < 10-4), more frequently diagnosed within the first month of symptoms (p < 10-4) and associated with comorbidities (p < 10-4). SA NVIE was more often complicated with stroke (p = 0.0009) and emboli (p = 0.008). By contrast the frequencies of cardiac failure and intracardiac abscess were the same in the two groups. EVS and 60-day in-hospital mortality rates were lower (34.2% vs. 50.1%, p<10-4) and higher (26.5% vs. 11.9%, p<10-4), respectively. In multivariate analysis, the probability of EVS was significantly lower in SA NVIE (HR 0.66, 95 CI 0.54-0.80, p<0.0001) and the probability of in-hospital death was significantly higher (HR 1.68, 95 CI 1.28-2.22, p<0.0001), which was true both in operated and non-operated patients. Conclusion: This study confirms that SA NVIE is associated with higher rates of comorbidities and mortality. It is also associated with a lower rate of EVS, which is neither explained by a higher frequency of comorbidities/complications that would contraindicate surgery nor by a lower frequency of conditions that would require surgery.
    International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2009; 33.
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2009; 33.
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    ABSTRACT: The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P = 0.01), sea (P < 0.01), and pvl (P = 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P = 0.03), map/eap (P = 0.05), fnbB (P = 0.11), tst (P = 0.02), sea (P = 0.04), sed (P = 0.04), seg (P = 0.11), sej (P = 0.11), agr (P = 0.09), V8 (P = 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P = 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.
    Journal of clinical microbiology 02/2008; 46(2):678-84. · 4.16 Impact Factor
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    ABSTRACT: Background: Telavancin (TLV) is a rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action that is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Methods: We conducted two identical multinational, parallel, randomized, double blind, active control, Phase 3 studies (ATLAS I & II) with a pre-specified pooled analysis design. Patients ≥ 18 years of age with cSSSI caused by suspected or confirmed Gram-positive pathogens were randomized to receive either vancomycin (VAN) 1 g IV q 12h or TLV 10 mg/kg IV q 24h for 7-14 days. Results: In the ATLAS I study, a total of 855 patients (VAN 429, TLV 426) were randomized at 40 sites in 8 countries, and received at least one dose of study medication. Overall 25% of the patients were diabetic, 19% were ≥65 years old, 44% had abscesses, 37% had cellulitis, and 36% had MRSA as a baseline pathogen. Baseline demographic, clinical characteristics and length of therapy were similar between the two groups. The primary efficacy objective of non-inferiority was met. In the clinically evaluable (CE) population, a successful clinical response was achieved in 86.5 % and 87.9 % of patients receiving VAN and TLV, respectively. In microbiologically evaluable (ME) patients with documented MRSA infection, successful clinical response was achieved in 85.5 % for VAN and 87% for TLV. In ME patients with documented methicillin-susceptible S. aureus infection, the rates were 84.6 % for VAN and 89.9 % for TLV. The proportions of patients who died, experienced a serious adverse event, or who discontinued the study drug due to an adverse event were similar between the two groups. Conclusion: These data support the efficacy and safety of once-daily telavancin in the treatment of Gram-positive cSSSI.
    Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
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    ABSTRACT: Background: American Heart Association Guidelines recommend considering the addition of initial GENT to semisynthetic penicillins (SSP) or vancomycin (V) as standard treatment (STD) for SAIE. Methods: STD consisting of SSP 2 g IV q4 or V 1 g IV q12 both with initial GENT 1 mg/kg IV q8 was compared to therapy with daptomycin (D) at 6mg/kg iv qd in a randomized controlled trial of therapy for SAB/SAIE. Creatinine clearance (CrCl) of ≥ 30 mL/min was required for study entry. Adverse events (AEs) were collected and CrCl was calculated at baseline and at periodic intervals. Results: 92.5% VAN and 93.7% SSP patients (pts) received GENT for a median of 5 days. Renal toxicity AEs including acute renal failure, acute tubular necrosis, worsening of chronic insufficiency, toxic nephropathy, interstitial nephritis and azotemia occurred in 18.1% of pts receiving STD vs. 6.7% of pts receiving D (p = 0.006). Among pts ≥ 65 years old, 31.6% of STD pts had renal AEs vs 6.7% of D pts (p = 0.015). Significant differences in the mean increases in serum Cr in the STD group were observed as early as day 4 of therapy and were most pronounced on day 7. Analysis of change in CrCl from baseline showed that 3.4% D and 10.8% STD pts had CrCl decrease to < 30 mL/min (p = 0.038). Time to decreased renal function (decrease in CrCl to <50 mL/min or >10 mL/min decrease if baseline was <50 mL/min) occurred early for STD compared to D pts (p=0.003) and persisted during treatment (p=0.002). Conclusion: Combination therapy for SAB and SAIE with SSP or V plus GENT is nephrotoxic. Given the limited existing data supporting the benefit of GENT in native valve SAIE, consideration should be given to severely limiting use of GENT for these infections.
    Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
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    ABSTRACT: The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation.
    The American Journal of Cardiology 10/2005; 96(7):976-81. · 3.21 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2004; 43(5).
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    ABSTRACT: Previous studies give conflicting results regarding the effect of age on outcomes in Staphylococcus aureus bacteremia (SAB). These studies have been limited by retrospective design or small sample size. We conducted a prospective cohort study of 385 patients with SAB aged 18 to 90 years. The setting was a large academic medical center. We observed patients from diagnosis of SAB to discharge or death. Discharged patients were contacted 12 weeks after their first positive culture findings. Data were collected on demographics, comorbid conditions, focus of infection, length of stay, and outcome. Primary outcomes were total mortality and death due to SAB. Comparisons were made between 145 patients, aged 66 to 90 years, and 240 patients, aged 18 to 60 years. Forty-three (29.7%) of the elderly patients and 36 (15%) of the younger patients died. Death directly attributable to SAB occurred in 21 (14.5%) older and 15 (6.3%) younger patients. After adjusting for confounding variables, older patients continued to have higher total mortality (odds ratio, 2.21; 95% confidence interval, 1.32-3.70), and higher mortality from SAB (odds ratio, 2.30; 95% confidence interval, 1.13-4.69). Infection with methicillin-resistant S aureus was associated with higher total mortality in the elderly (odds ratio, 2.59; 95% confidence interval, 1.23-5.43). Staphylococcus aureus bacteremia among the elderly is associated with high mortality. Both total mortality and mortality directly attributable to SAB are more than twice as likely in older patients. Infection with methicillin-resistant S aureus carries a worse prognosis than infection with methicillin-sensitive S aureus in the elderly.
    Archives of Internal Medicine 07/1999; 159(11):1244-7. · 11.46 Impact Factor
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Publication Stats

217 Citations
38.90 Total Impact Points

Institutions

  • 1999–2014
    • Duke University Medical Center
      • • Division of Infectious Diseases
      • • Department of Biostatistics and Bioinformatics
      • • Duke Clinical Research Institute
      • • Department of Medicine
      Durham, North Carolina, United States
  • 2008
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 2005
    • Corporació Sanitària Parc Taulí
      • Hospital de Sabadell
      Catalonia, Spain