Andre C Kalil's research while affiliated with University of Nebraska Medical Center and other places

Publications (291)

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OBJECTIVES:. Pneumonia remains a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of coinfection. Further investigation into the impact of bronchoalveolar lavage (BAL) sampling methodology and efficient clinical utilization of microbiological analyses is needed to guide the management...
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Background Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. Methods In this random...
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Solid organ transplant (SOT) recipients carry a lifelong high risk of developing severe infections, including opportunistic, community, and hospital acquired infections. While major progress has been made in immunosuppressive drugs to prevent allograft rejection, the risk of infections remains always present because the continuing necessity of immu...
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Background Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. Methods We did a double-blind,...
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Sepsis is a complex disease stemming from a dysregulated immune response toward an infectious agent. In transplantation, sepsis remains one of the leading causes of morbidity and mortality. Solid organ transplant recipients have impaired adaptive immunity due to immunosuppression required to prevent rejection. Immunosuppression has unintended conse...
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Purpose of review: Janus Kinase (JAK) inhibitors have been successfully utilized in the clinical treatment of several rheumatologic (e.g. rheumatoid arthritis) and inflammatory diseases (e.g. hemophagocytic lymphohistiocytosis). Based on the growing evidence that moderate and severe COVID-19 infections are associated with a dysregulated inflammato...
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We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. Design: We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected...
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Background While rheumatoid arthritis (RA) and its treatments are associated with an increased infection risk, it remains unclear whether these factors impact the risk or severity of COVID‐19. Methods We conducted a matched cohort study using national Veterans Affairs data. Among non‐deceased individuals on January 1, 2020 who received VA care in...
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BACKGROUND Angiotensin receptor blockers (ARBs) and/or angiotensin converting enzyme (ACE) inhibitors could alter mortality of COVID-19, but existing meta-analyses which combined crude and adjusted results may be confounded by comorbidities being more common in ARBs/ACE inhibitors users. METHODS We searched PubMed/MEDLINE/Embase for cohort studies...
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Background Grading of Recommendations Assessment, Development, and Evaluation (GRADE) is a systematic approach to grading strength of recommendation (SOR) and quality of evidence (QOE) for guideline recommendations. We aimed to assess the relationship between SOR and QOE in current Infectious Diseases Society of America (IDSA) guidelines. Methods...
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Background Pneumonia is a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of co-infection. However, the impact of methodology to obtain lower respiratory samples along with the utility of various microbiological diagnostic testing remains unclear. Methods A single-center retrospecti...
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BACKGROUND Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults w...
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BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults...
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Objective To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID‐19) pandemic. Methods A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report w...
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Introduction Intensive Care Units (ICU) are among the hospital wards exhibiting the highest prevalence of antimicrobial resistance (AMR), and resulting impact on patient outcomes. Antimicrobial resistance surveillance and antimicrobial stewardship (AMS) programs play a pivotal role in promoting interventions tailored to optimize infection diagnosis...
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Background Prior meta-analyses suggested that treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) with empiric carbapenems was associated with lower mortality rates but with higher rates of clinical failure for Pseudomonal pneumonia. We undertook an updated meta-analysis with sensitivity analyses and meta-reg...
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Objectives Coronavirus disease 19 (COVID-19) is a major cause of hospital admission and represents a challenge for patient management during intensive care unit (ICU) stay. We aimed to describe the clinical course and outcomes of COVID-19 pneumonia in critically ill patients. Methods We performed a systematic search of peer-reviewed publications i...
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Background: Antibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney...
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In Reply A total of 14 studies (8 randomized trials and 6 observational studies) have already evaluated the effects of high-dose vitamin C, thiamine, and steroids in more than 2000 patients with sepsis in 10 different countries, and the overall results have been disappointing.¹ In addition, 12 other trials are now completed according to ClinicalTri...
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Objective To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID ‐19) pandemic. Methods A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report...
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Sepsis remains among the most common complications from infectious diseases worldwide. The morbidity and mortality rates associated with sepsis range from 20% to 50%. The advances in care for patients with an immunocompromised status have been remarkable over the last 2 decades, but sepsis continues to be a major cause of death in this population I...
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Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract in...
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The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because...
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Objective To provide guidance to rheumatology providers on the management of adult rheumatic disease patients in the context of the COVID‐19 pandemic. Methods A task force, including 10 rheumatologists and 4 infectious diseases specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly genera...
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The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good govern...
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Patients with cystic fibrosis (CF) experience multiple pulmonary exacerbations throughout their lifetime, resulting in repeated antibiotic exposure and hospital admissions. Reliable diagnostic markers to guide antibiotic treatment in patients with CF, however, are lacking. Given that the CF airway is characterized by persistent and frequent bacteri...
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The use of vitamin C for treatment of patients with sepsis has generated substantial interest and controversy. In 2017, a single-center observational study suggested that the combination of high-dose vitamin C, thiamine, and hydrocortisone in conjunction with usual care was associated with reduced mortality (8.5% for combination treatment vs 40.4%...
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Abstract Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual’s contac...
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Background The understanding of pneumonia epidemiology has been evolving in recent years with an increased awareness of viral respiratory pathogens since the introduction of respiratory pathogen panels. However, epidemiological and clinical data on pneumonia due to co-infection are lacking. Methods A single-center retrospective analysis of mechani...
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Background Pneumonia epidemiology is increasingly showing the presence of co-infection due to the utilization of emerging diagnostic testing modalities such as multiplex polymerase chain reaction (PCR) panels. However, the prevalence and clinical significance of co-infection with respect to host immune status remain unclear. Methods A single-cente...
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Objectives To identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD). Methods Patients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous...
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Background: The increasing prevalence of ventilator-associated pneumonia (VAP) due to either multidrug-resistant (MDR) organisms or infections with limited treatment options (i.e. susceptible to only aminoglycosides or colisitin) coupled with a dearth of new antimicrobials has led clinicians to pursue alternative management strategies including th...
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The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.
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The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.
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Purpose Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality. Methods Narrative revie...
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Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked...
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Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures...
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Background Cytomegalovirus (CMV) resistance is an emerging problem in solid organ transplant recipients. Risk factors are not well defined. Methods Recipients with CMV viremia of solid organ transplants who underwent CMV resistance testing between January 2010 and March 2016 were divided in 2 groups: proven CMV resistance and refractory CMV infect...
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Background The importance of adenoviruses (AdV) in the immunocompromised population has been more recognized in recent decades. We aimed to assess the risk factors and outcomes associated with AdV in solid organ transplant recipients. Methods This was a retrospective cohort study of solid organ transplant recipients who tested positive for AdV bet...
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Background: Severe infections are among the most common causes of death in immunocompromised patients admitted to the intensive care unit. The epidemiology, diagnosis, and treatment of these infections has evolved in the last decade. Aims: We aim to provide a comprehensive review of these severe infections in this population. Sources: Review o...
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Background: C. difficile is the most common cause of healthcare-associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well defined. The aim of our study was to assess specific risk factors for CDI in ITR. Methods: This is a 1:3 case-control study that included 29 ITR who...
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IDSA did not endorse the 2016 Surviving Sepsis Campaign Guidelines despite being represented in the working group that drafted the guidelines document. Leadership from IDSA, the Surviving Sepsis Campaign Guidelines, and the Society of Critical Care Medicine had numerous amicable discussions primarily regarding the bolded, rated guidelines recommend...
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The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated fro...
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Background Cytomegalovirus (CMV) infections have a significant impact on morbidity and mortality of solid organ transplant (SOT) recipients. Acquisition of CMV resistance is an emerging problem. Risk factors associated for CMV resistance are not well defined. Methods We selected SOT recipients who underwent CMV resistance testing between January 2...
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Background Infections represent the major cause of morbidity and mortality among solid organ transplant recipients. In renal transplantation, infections are the second leading cause of death after cardiovascular disease. The aim of our study was to describe the incidence of bloodstream infections after kidney transplantation and to describe the eti...