Andre C Kalil

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

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Publications (110)661 Total impact

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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; · 1.63 Impact Factor
  • Andre C Kalil
    08/2014; 14(8):674–675.
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    ABSTRACT: 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.
    Transplantation 07/2014; · 3.78 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; · 4.57 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; · 2.07 Impact Factor
  • Michael Klompas, Andre C Kalil
    Critical care medicine 03/2014; 42(3):722-3. · 6.37 Impact Factor
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    ABSTRACT: Aims: The aims of this study were to determine a mechanism and general timeline forstatin related anti-inflammatory activity. Methods: Healthy male subjects received rosuvastatin (20 mg daily) for 3 weeks. Blood samples before and after treatment were collected forclinical laboratories and research procedures.Toll-like receptor-4 (tlr-4) expression on blood monocytes was measured using flow cytometry before and after rosuvastatin treatment. Inflammatory molecules were measured before and after rosuvastatin and after blood samples were incubated for 3 hours with or without lipopolysaccharide. Plasma was collected and analyzed for IL-6, TNF, IL-8, IGF-1, and sCD14. Comparisons were made using Mann-Whitney rank sum test and paired Student's t-test with significance defined as p.
    Current pharmaceutical design 01/2014; · 4.41 Impact Factor
  • Andre C Kalil, Trevor C Schooneveld
    The Lancet 01/2014; 383(9911):29-30. · 39.06 Impact Factor
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    ABSTRACT: Background. Prophylactic and preemptive strategies are used to prevent cytomegalovirus infections after solid organ transplantation. We assessed the safety and efficacy of both strategies for CMV prevention. Methods. DerSimonian and Laird random-effects model was used for pooling the data and Q statistic and I-squared methods were used to assess statistical heterogeneity. Results. Twenty studies (2744 patients) were selected for the direct analysis and 20 studies (2544 patients) for the indirect analysis. The odds of CMV syndrome (OR=1.10;95%CI:0.60-2.03;p=0.757;Q=18.55;I(2)=51.49%) and disease (OR=0.77;95%CI:0.41-1.47;p=0.432;Q=32.71;I(2)=44.97%.) were not significantly different between strategies. The odds of developing late-onset CMV infections were higher for the prophylactic compared to the preemptive strategy (OR=6.21;95%CI:2.55-15.20;p<0.0001;Q=9.66;I(2)=37.9%). The odds of CMV viremia were lower for prophylaxis (OR=0.42;95%CI:0.24-0.74;p=0.003;Q=48.10;I(2)=75.1%) than preemptive therapy. No differences between strategies were noted for: graft loss (OR=0.88;95%CI:0.37-2.13;p=0.779;Q=13.03,I(2)=38.62%), graft loss censored for death (OR=0.73;95%CI:0.17-3.21;p=0.679;Q=4.48;I(2)=55.32%), acute rejection (OR=0.93;95%CI:0.70-1.24;p=0.637;Q=12.99;I(2)=7.61%) and mortality (OR=0.80;95%CI:0.56-1.14;p=0.220;Q=8.76;I(2)=0%). Other infections (HSV, VZV, bacterial and fungal infections) were not significantly different between strategies. Leukopenia (OR=1.97;95%CI:1.39-2.79;p=0.0001;Q=7.10;I(2)=0%) and neutropenia (OR=2.07;95%CI:1.13-3.78;p=0.018;Q=6.77;I(2)=11.40%) were more frequent with prophylaxis than preemptive strategy. The results of direct and indirect comparisons were consistent. Conclusions. Prophylaxis was associated with less early post-transplant viremia, but with significantly more late-onset CMV infections and side effects - leukopenia and neutropenia, than the preemptive strategy. Both preventive strategies showed similar efficacy in preventing CMV syndrome and disease, with no differences regarding rejection, graft loss, death and opportunistic infections.
    Clinical Infectious Diseases 01/2014; · 9.37 Impact Factor
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    Diana F Florescu, Andre C Kalil
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    ABSTRACT: Severe sepsis is traditionally associated with bacterial diseases. While fungi and parasites can also cause sepsis, they are significantly less common than bacterial causes. However, viruses are becoming a growing cause of severe sepsis worldwide. Among these viruses, influenza is crossing all geographic boundaries and is causing larger epidemics and pandemics. As a consequence, more critically ill patients with severe sepsis caused directly by influenza viruses, or indirectly by influenza-induced secondary bacterial infections are being admitted to hospitals worldwide. This manuscript aims to provide a pathophysiological and clinical update on the link between influenza and severe sepsis.
    Virulence 11/2013; 5(1). · 2.79 Impact Factor
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    ABSTRACT: Practice variation regarding cytomegalovirus (CMV) prevention and treatment across intestinal transplantation (IT) programs is unknown. An electronic survey was sent to IT programs registered with the Intestinal Transplant Association. Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. Seventy-seven percent of IT programs responded to the survey. For CMV D+/R- recipients, 39.1% programs used universal prophylaxis (UP), 8.7% preemptive strategy (PE), and 52.2% hybrid strategy. For CMV R+ recipients, 45.8% programs used UP, 12.5% PE, 37.1% hybrid strategy, and 4.2% none. For CMV D-/R- recipients, 39.1% programs used UP, 21.7% PE, 26.1% hybrid strategy, and 13% none. Frequency of monitoring for PE was weekly 71.4% of programs, every 2 weeks 21.4%, and monthly 7.1%. For CMV viremia, syndrome and disease, the most common first-line agents used were ganciclovir (100% and 96.2%) and valganciclovir (23.1%) and the second-line agent was foscarnet (73.1% and 84.6%). Immunoglobulins were administered in 65.4% of the programs for pneumonia (69.2%), meningoencephalitis (50%), enteritis (46.2%), colitis (38.5%), syndrome (42.3%), viremia (30.8%), and resistant/refractory infections (11.5%). Prophylaxis and hybrid strategy were the most commonly used. Treatment practices were consistent and mainly involved ganciclovir as first-line agent and foscarnet as second-line agent. The use of immunoglobulins appeared to be more common than in other allografts.
    Transplantation 10/2013; · 3.78 Impact Factor
  • Andre C Kalil
    Critical care medicine 10/2013; 41(10):2458-60. · 6.37 Impact Factor
  • Andre C Kalil
    Critical care medicine 09/2013; 41(9):2232-3. · 6.37 Impact Factor
  • Andre C Kalil, Marius C Florescu
    Critical care medicine 09/2013; 41(9):2244-5. · 6.37 Impact Factor
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    ABSTRACT: Hypogammaglobulinemia has been described after solid organ transplantation and has been associated with increased risk of infections. The aim of the study was to evaluate the rate of severe hypogammaglobulinemia and its relationship with the risk of infections during the first year posttransplantation. Eighteen studies (1756 patients) that evaluated hypogammaglobulinemia and posttransplant infections were included. The data were pooled using the DerSimonian and Laird random-effects model. Q statistic method was used to assess statistical heterogeneity. Within the first year posttransplantation, the rate of hypogammaglobulinemia (IgG < 700 mg/dL) was 45% (95% CI: 0.34-0.55; Q = 330.1, p < 0.0001), the rate of mild hypogammaglobulinemia (IgG = 400-700 mg/dL) was 39% (95% CI: 0.22-0.56; Q = 210.09, p < 0.0001) and the rate of severe hypogammaglobulinemia (IgG < 400 mg/dL) was 15% (95% CI: 0.08-0.22; Q = 50.15, p < 0.0001). The rate of hypogammaglobulinemia by allograft type: heart 49% (21%-78%; Q = 131.16, p < 0.0001); kidney 40% (30%-49%; Q = 24.55, p = 0.0002); liver 16% (0.001%-35%; Q = 14.31, p = 0.0002) and lung 63% (53%-74%; Q = 6.85, p = 0.08). The odds of respiratory infection (OR = 4.83; 95% CI: 1.66-14.05; p = 0.004; I(2) = 0%), CMV (OR = 2.40; 95% CI: 1.16-4.96; p = 0.02; I(2) = 26.66%), Aspergillus (OR = 8.19; 95% CI: 2.38-28.21; p = 0.0009; I(2) = 17.02%) and other fungal infections (OR = 3.69; 95% CI: 1.11-12.33; p = 0.03; I(2) = 0%) for patients with IgG <400 mg/dL were higher than the odds for patients with IgG >400 mg/dL. The odds for 1-year all-cause mortality for severe hypogammaglobulinemia group was 21.91 times higher than those for IgG >400 mg/dL group (95% CI: 2.49-192.55; p = 0.005; I(2) = 0%). Severe hypogammaglobulinemia during the first year posttransplantation significantly increased the risk of CMV, fungal and respiratory infections, and was associated with higher 1-year all-cause mortality.
    American Journal of Transplantation 08/2013; · 6.19 Impact Factor
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    Andre C Kalil, Diana F Florescu
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    ABSTRACT: Despite the same manufacturer, the same drotrecogin alfa activated dose, and the same placebo-controlled design, the negative result from the PROWESS-SHOCK trial contradicted the survival benefit observed in the PROWESS trial. We hypothesize that the different results were due to factors other than the experimental therapy and performed an analysis of the clinical heterogeneity (differences related to the trials' clinical aspects) and the statistical heterogeneity (differences related to the trials' statistical aspects) between these trials. Baseline characteristics and co-interventions were analyzed by chi-square testing and mortality was analyzed by random-effects modeling and I2. Our findings show that clinical variables presented significant heterogeneity, and that up to 90% of the mortality differences between both trials were not due to chance. These results demonstrate that PROWESS and PROWESS-SHOCK are not comparable trials due to the highly significant clinical and statistical heterogeneity. We propose a new and pragmatic solution.
    Critical care (London, England) 07/2013; 17(4):167. · 4.72 Impact Factor
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    ABSTRACT: To the Editor: Van Nood et al. (Jan. 31 issue)(1) found fecal microbiota therapy to be superior to vancomycin for the treatment of recurrent Clostridium difficile infection, but the results of their study should be interpreted with caution. Small, index trials such as this one are vulnerable to exaggerated treatment effects, and subsequent trials typically show decreased effects.(2) Even though the trial was randomized, the results may have been influenced by inequalities among the three treatment groups in terms of either the number of pretreatment recurrences of C. difficile infection or post-treatment exposure to an antimicrobial agent or proton-pump inhibitor . . .
    New England Journal of Medicine 05/2013; 368(22):2143-2145. · 51.66 Impact Factor
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    ABSTRACT: Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response. To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality. We performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo, with n = 1304 and n = 657 patients, respectively. The primary end point was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months after beginning treatment. Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = .59; hazard ratio, 1.05; 95% CI, 0.88-1.26; difference in mortality rate, -1.1; 95% CI, -5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = .79 (hazard ratio, 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Among patients with severe sepsis, the use of eritoran, compared with placebo, did not result in reduced 28-day mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00334828.
    JAMA The Journal of the American Medical Association 03/2013; 309(11):1154-62. · 29.98 Impact Factor
  • Andre C Kalil, Steven P Larosa
    The Lancet Infectious Diseases 02/2013; 13(2):110-1. · 19.97 Impact Factor
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    ABSTRACT: We describe two patients who developed gastrointestinal bleeding due to cytomegalovirus (CMV) colitis after placement of a HeartMate II left ventricular assist device (LVAD). We aim to raise awareness of CMV colitis as a possible cause of gastrointestinal bleeding after LVAD placement and discuss potential mechanisms for CMV reactivation and areas for future research.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 01/2013; · 2.17 Impact Factor

Publication Stats

2k Citations
661.00 Total Impact Points

Institutions

  • 2007–2014
    • University of Nebraska Medical Center
      • Division of Infectious Diseases
      Omaha, Nebraska, United States
    • Northwestern University
      • Division of General Internal Medicine and Geriatrics
      Evanston, IL, United States
  • 2005–2013
    • University of Nebraska at Omaha
      • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 2012
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
  • 2010
    • State University of New York
      New York City, New York, United States
  • 2005–2009
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2008
    • University of Houston
      Houston, Texas, United States
  • 2006
    • National Institutes of Health
      • Critical Care Medicine Department
      Bethesda, MD, United States
  • 2004
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States