Andre C Kalil

University of Nebraska Medical Center, Omaha, Nebraska, United States

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Publications (142)861.59 Total impact

  • Kristina L Bailey · Andre C Kalil
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    ABSTRACT: Ventilator-associated pneumonia (VAP) due to multidrug-resistant bacteria (MDR) is an emerging problem worldwide. Both gram-negative and gram-positive microorganisms are associated with VAP. We first describe the magnitude of the problem of MDR VAP followed by its clinical impact on survival outcomes, with the primary aim to review the optimal antibiotic choices to treat patients with MDR VAP. We discuss the challenges of intravenous and inhaled antibiotic treatments, as well as of monotherapy and combination antimicrobial therapies.
    Current Infectious Disease Reports 08/2015; 17(8):494. DOI:10.1007/s11908-015-0494-5 · 1.68 Impact Factor
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    ABSTRACT: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease. Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital). Not applicable. Not applicable. Not applicable. In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.
    Critical care medicine 07/2015; DOI:10.1097/CCM.0000000000001197 · 6.31 Impact Factor
  • Andre C Kalil · Steven M Opal
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    ABSTRACT: The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients.
    Current Infectious Disease Reports 06/2015; 17(6):487. DOI:10.1007/s11908-015-0487-4 · 1.68 Impact Factor
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    ABSTRACT: From 2014 to early May 2015, >26,000 Ebola virus disease (EVD) cases were reported from West Africa. We present an EVD patient who received brincidofovir and convalescent plasma treatment. The relative contributions of supportive care, investigational therapies, or the patient's immune response upon the patient's survival could not be determined. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    Clinical Infectious Diseases 05/2015; 61(6). DOI:10.1093/cid/civ395 · 8.89 Impact Factor
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    Uriel Sandkovsky · Andre C. Kalil · Diana F. Florescu
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    ABSTRACT: Procalcitonin has been increasingly used as a biomarker of bacterial infection and as a tool to guide antimicrobial therapy, especially in lower respiratory tract and bloodstream infections. Despite its increased use, data in patients with solid organ transplants is limited. Even without the presence of infection, procalcitonin increases as a result of surgical procedures during transplantation, implantation of devices and use of induction immunosuppressive therapy. The risk of infection is also higher in solid organ transplant recipients when compared to the general population. Monitoring PCT in the early post-transplant period seems to be promising method for early detection of infectious complications. It has been shown that elevated PCT levels after 1 week of transplantation are correlated with infectious complications. PCT may be a useful adjunctive biomarker that may improve early identification and guide appropriate treatment of infection or rejection, with the potential to further improve clinical outcomes. The use of serial PCT measurements may be more reliable than single values. It is important to recognize which factors may lead to procalcitonin increases in the post-transplantation period, which in turn will help understand the kinetics of this useful biomarker in this important patient population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 05/2015; 29(8). DOI:10.1111/ctr.12568 · 1.52 Impact Factor
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    ABSTRACT: This report will describe the preparations for and the provision of care of two patients with Ebola virus disease in the biocontainment unit at the University of Nebraska Medical Center. Patient medical records. Not applicable. Not applicable. Not applicable. Safe and effective care of patients with Ebola virus disease requires significant communication and planning. Adherence to a predetermined isolation protocol is essential, including proper donning and doffing of personal protective equipment. Location of the patient care area and the logistics of laboratory testing, diagnostic imaging, and the removal of waste must be considered. Patients with Ebola virus disease are often dehydrated and need adequate vascular access for fluid resuscitation, nutrition, and phlebotomy for laboratory sampling. Advanced planning for acute life-threatening events and code status must be considered. Intensivist scheduling should account for the significant amount of time required for the care of patients with Ebola virus disease. With appropriate precautions and resources, designated hospitals in the United States can safely provide care for patients with Ebola virus disease.
    Critical Care Medicine 03/2015; 43(6). DOI:10.1097/CCM.0000000000000935 · 6.31 Impact Factor
  • Andre C Kalil · Mark E Rupp · Diana F Florescu
  • Andre C Kalil
    Critical Care Medicine 03/2015; 43(3):694-695. DOI:10.1097/CCM.0000000000000838 · 6.31 Impact Factor
  • Andre C Kalil · Uriel S Sandkovsky
    Annals of internal medicine 02/2015; 162(4):JC7. DOI:10.7326/ACPJC-2015-162-4-007 · 17.81 Impact Factor
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    ABSTRACT: Importance Staphylococcus aureus bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health.Data Sources PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014.Study Selection Studies reporting mortality and vancomycin MIC in patients with SAB were included.Data Extraction and Synthesis Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses.Main Outcomes and Measures All-cause mortality.Findings Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (<1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, −2.3% to 5.6%]; P = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, −2.9% to 4.6%]; P = .65). In studies that included only methicillin-resistant S aureus infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, −2.3% to 5.5%]; P = .41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin.Conclusions and Relevance In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.
    JAMA The Journal of the American Medical Association 10/2014; 312(15):1552-1564. DOI:10.1001/jama.2014.6364 · 35.29 Impact Factor
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    ABSTRACT: Background: Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. Methods: This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. Results: Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). Conclusions: The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.
    Clinical Infectious Diseases 10/2014; 60(2). DOI:10.1093/cid/ciu789 · 8.89 Impact Factor
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    Antimicrobial Agents and Chemotherapy 10/2014; 58(10):6342. DOI:10.1128/AAC.04097-14 · 4.48 Impact Factor
  • Andre C Kalil · Junfeng Sun
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    ABSTRACT: Objectives: To review Bayesian methodology and its utility to clinical decision making and research in the critical care field. Data source and study selection: Clinical, epidemiological, and biostatistical studies on Bayesian methods in PubMed and Embase from their inception to December 2013. Data synthesis: Bayesian methods have been extensively used by a wide range of scientific fields, including astronomy, engineering, chemistry, genetics, physics, geology, paleontology, climatology, cryptography, linguistics, ecology, and computational sciences. The application of medical knowledge in clinical research is analogous to the application of medical knowledge in clinical practice. Bedside physicians have to make most diagnostic and treatment decisions on critically ill patients every day without clear-cut evidence-based medicine (more subjective than objective evidence). Similarly, clinical researchers have to make most decisions about trial design with limited available data. Bayesian methodology allows both subjective and objective aspects of knowledge to be formally measured and transparently incorporated into the design, execution, and interpretation of clinical trials. In addition, various degrees of knowledge and several hypotheses can be tested at the same time in a single clinical trial without the risk of multiplicity. Notably, the Bayesian technology is naturally suited for the interpretation of clinical trial findings for the individualized care of critically ill patients and for the optimization of public health policies. Conclusions: We propose that the application of the versatile Bayesian methodology in conjunction with the conventional statistical methods is not only ripe for actual use in critical care clinical research but it is also a necessary step to maximize the performance of clinical trials and its translation to the practice of critical care medicine.
    Critical Care Medicine 10/2014; 42(10):2267-2277. DOI:10.1097/CCM.0000000000000576 · 6.31 Impact Factor
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    ABSTRACT: Background Severe hypogammaglobulinemia (IgG<400 mg/dL) has adverse impact on mortality during the first year post-transplantation. The aim of the study was to determine whether increasing IgG levels to >400mg/dl improved outcomes.Methods Kaplan-Meier analyses were performed to estimate survival, log-rank test to compare survival distributions between groups and Fisher's exact test to determine the association between hypogammaglobulinemia and rejection or graft loss.Results37 solid organ transplant (SOT) recipients were included. Hypogammaglobulinemia was diagnosed at median of 5.6months (range:0-291.8months) post-transplantation. Types of transplants: liver-small bowel (17); liver-small bowel-kidney (2); liver (5); small bowel (4); liver-kidney (1); kidney/kidney-pancreas (3); heart (3); heart-kidney (1); heart-lung (1). The 3-year survival after the diagnosis of hypogammaglobulinemia was 49.5% (95%CI:32.2-64.6%). Patients were dichotomized based upon IgG level at last follow-up: IgG>400mg/dL (23patients) and IgG<400mg/dL (14patients). There was no evidence of a difference in survival (p=0.44), rejection rate (p=0.44) and graft loss censored for death (p=0.99) at one year between these 2 groups. There was no difference in survival between patients receiving or not immunoglobulin (p=0.99) or cytomegalovirus hyperimmunoglobulin (p=0.14).Conclusion Severe hypogammaglobulinemia after SOT is associated with high mortality rates, but increasing IgG levels to >400mg/dL did not seem to translate in better patient or graft survival in this cohort.This article is protected by copyright. All rights reserved.
    Clinical Transplantation 09/2014; 28(11). DOI:10.1111/ctr.12458 · 1.52 Impact Factor
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    ABSTRACT: Background Acute flaccid paralysis surveillance (AFP) is an essential strategy of the WHO’s Polio Eradication Initiative. This is the first study conducted to estimate the incidence, etiology, distribution, and surveillance performance of AFP in Iraq. Methods Surveillance data about the AFP cases under the age of 15 years reported from Iraq during January 1997 to December 2011 were depended in the current study. Results A total of 4974 cases of AFP were reported from Iraq during the study period, with an annual incidence of 2.5/100,000 population. Guillain-Barré syndrome represented more than half of the reported cases (N = 2611, 52.5%), followed by traumatic neuritis (N = 715, 14.4%), and other CNS infections (N = 292, 5.9%). Poliomyelitis accounted for 166 (3.3%) of cases, the last reported case being in January 2000. Surveillance performance showed that all, but two, indicators were below the required WHO recommended levels. Conclusions AFP surveillance remains the gold standard method for poliomyelitis detection. It witnessed dramatic changes over the last two decades. This has raised people’s and clinicians’ awareness to the importance of promptness in notifying suspected cases and timely transportation of stool specimens to the National Poliovirus Laboratory in Baghdad, or alternatively having more than one laboratory for poliovirus detection in the country, all of which are very useful measures to increase the surveillance performance in the country.
    BMC Infectious Diseases 08/2014; 14(1):448. DOI:10.1186/1471-2334-14-448 · 2.61 Impact Factor
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    Andre C Kalil
    The Lancet Infectious Diseases 08/2014; 14(8):674–675. DOI:10.1016/S1473-3099(14)70836-9 · 22.43 Impact Factor
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    ABSTRACT: The lungs are a major target for infection and a key battleground in the fight against the development of antimicrobial drug-resistant pathogens. Ventilator-associated pneumonia (VAP) is associated with mortality rates of 24-50%. The optimal duration of antibiotic therapy against VAP is unknown, but prolonged courses are associated with the emergence of bacterial resistance. De-escalation strategies in which treatment is discontinued based on signs of clinical resolution, fixed durations of therapy (generally 7-8 d), or serum procalcitonin responses have been shown to decrease antibiotic consumption. Outcomes are comparable to longer treatment courses, with the possible exception of VAP due to nonfermenting, gram-negative bacilli such as Pseudomonas aeruginosa. Staphylococcus aureus is a leading cause of VAP and other infections. Outcomes after S. aureus infection are shaped by the interplay between environmental, bacterial, and host genetic factors. It is increasingly clear that mechanisms of pathogenesis vary in different types of S. aureus infections. Genome-scale studies of S. aureus strains, host responses, and host genetics are redefining our understanding of the pathogenic mechanisms underlying VAP. Genome-sequencing technologies are also revolutionizing our understanding of the molecular epidemiology, evolution, and transmission of influenza. Deep sequencing using next-generation technology platforms is defining the remarkable genetic diversity of influenza strains within infected hosts. Investigators have demonstrated that antiviral drug-resistant influenza may be present prior to the initiation of treatment. Moreover, drug-resistant minor variant influenza strains can be transmitted from person to person in the absence of selection pressure. Studies of lung infections and the causative pathogens will remain at the cutting edge of clinical and basic medical research.
    08/2014; 11(Supplement 4):S193-S200. DOI:10.1513/AnnalsATS.201402-069PL
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    ABSTRACT: Background We conducted a randomized and unblinded 2×2 sequential-factorial trial, composed of an induction arm (part 1) comparing single-dose (SD) versus divided-dose rabbit antithymocyte globulin (rATG), and a maintenance arm (part 2) comparing tacrolimus minimization versus withdrawal. We report the long-term safety and efficacy of SD-rATG induction in the context of early steroid withdrawal and tacrolimus minimization or withdrawal. Methods Patients (n=180) received 6 mg/kg rATG, SD or four alternate-day doses (1.5 mg/kg/dose), with early steroid withdrawal and tacrolimus or sirolimus maintenance. After 6 months targeted maintenance levels were tacrolimus, 2 to 4 ng/mL and sirolimus, 4 to 6 ng/mL or, if calcineurin inhibitor–withdrawn, sirolimus 8 to 12 ng/mL with mycophenolate mofetil 2 g two times per day. Primary endpoints were renal function (abbreviated modification of diet in renal disease) and chronic graft histopathology (Banff). Secondary endpoints included patient survival, graft survival, biopsy-proven rejection, and infectious or noninfectious complications. Results Follow-up averaged longer than 4 years. Tacrolimus or sirolimus and mycophenolate mofetil exposure was identical between groups. The SD-rATG associated with improved renal function (2-36 months; P<0.001) in deceased donor recipients. The SD-rATG associated with quicker lymphocyte, CD4 T cell, and CD4-CD8 recovery and fewer infections. Cox multivariate hazard modeling showed divided-dose–rATG (P=0.019), deceased donor (P=0.003), serious infection (P=0.0.018), and lower lymphocyte count (P=0.001) associated with increased mortality. Patients with all four covariates showed a 27-fold increased likelihood of death (P=0.00002). Chronic graft histopathology, rejection rates, and death-censored graft survival were not significantly different between groups. Conclusion The SD-rATG induction improves the 3-year renal function in recipients of deceased donor kidneys. This benefit, along with possibly improved patient survival and fewer infections suggest that how rATG is administered may impact its efficacy and safety.
    Transplantation 07/2014; 99(1). DOI:10.1097/TP.0000000000000250 · 3.83 Impact Factor
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    ABSTRACT: There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired (CAP) and healthcare-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from 1/2010-12/2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate if HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score adjusted multivariate analyses were performed. 521 patients (50.5% CAP, 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDRO were isolated in 20 (3.8%) patients overall, and MDRO occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. MDRO was not associated with HCAP classification (OR=1.95;95%CI 0.66-5.80;P=0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48h hospitalization in last 90 days). Independent predictors of MDRO included: P. aeruginosa colonization/infection in the previous year (OR=7.43;95%CI 2.24-24.61;P<0.001), antimicrobial use in the previous 90 days (OR=2.90;95%CI 1.13-7.45;P=0.027), admission from nursing home (OR=4.19;95%CI 1.55-11.31;P=0.005), and duration of hospitalization in the previous 90 or 180 days (P=0.013 and P=0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community-onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empiric overprescribing of antibiotics for MRSA and P. aeruginosa.
    Antimicrobial Agents and Chemotherapy 06/2014; 58(9). DOI:10.1128/AAC.02582-14 · 4.48 Impact Factor
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    ABSTRACT: Background: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. Methods: PRISMA guidelines were followed and random-effects models were performed. Results: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34-2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00-2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts.Conclusion The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.
    Expert Review of Anti-infective Therapy 05/2014; 12(7):1-16. DOI:10.1586/14787210.2014.917046 · 2.25 Impact Factor

Publication Stats

3k Citations
861.59 Total Impact Points


  • 2005–2015
    • University of Nebraska Medical Center
      • • Division of Infectious Diseases
      • • Department of Internal Medicine
      Omaha, Nebraska, United States
    • Baylor University
      Waco, Texas, United States
  • 2011–2014
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
  • 2006–2014
    • University of Nebraska at Omaha
      • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 2009
    • Georgetown University
      Washington, Washington, D.C., United States
    • University of Illinois, Urbana-Champaign
      • Department of Food Science and Human Nutrition
      Urbana, Illinois, United States
  • 2007–2008
    • University of Pittsburgh
      • Division of Infectious Diseases
      Pittsburgh, Pennsylvania, United States
  • 2005–2006
    • National Institutes of Health
      • Critical Care Medicine Department
      Bethesda, MD, United States