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Taneja V, Anand RS, El-Dallal M, Dong J, Desai N, Taneja I, Feuerstein JD. Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2024; 30:585-593. [PMID: 37300512 DOI: 10.1093/ibd/izad108] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Indexed: 06/12/2023]
Abstract
BACKGROUND Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. METHODS Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. RESULTS Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. CONCLUSION Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.
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Affiliation(s)
- Vikas Taneja
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Rajsavi S Anand
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mohammed El-Dallal
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Cambridge Health Alliance, Harvard Medical School, Boston, MA, USA
| | - Jeffrey Dong
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nisa Desai
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Isha Taneja
- Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Yin Z, Yu GP, Xu N, Jiang L, Huang F, Fan ZP, Wang ZX, Xuan L, Liu QF, Sun J. [Clinical observation of cidofovir in salvage therapy for cytomegalovirus infection in patients with haploid hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2020; 41:326-330. [PMID: 32447939 PMCID: PMC7364930 DOI: 10.3760/cma.j.issn.0253-2727.2020.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Indexed: 11/05/2022]
Affiliation(s)
- Z Yin
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - G P Yu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - N Xu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - L Jiang
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - F Huang
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Z P Fan
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Z X Wang
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - L Xuan
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Q F Liu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - J Sun
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Kaviani A, Ince D, Axelrod DA. Management of Antimicrobial Agents in Abdominal Organ Transplant Patients in Intensive Care Unit. CURRENT TRANSPLANTATION REPORTS 2020; 7:1-11. [PMID: 32432022 PMCID: PMC7222087 DOI: 10.1007/s40472-020-00268-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW Early diagnosis of infections and immediate initiation of appropriate antimicrobials are crucial in the management of patients before and after organ transplantation. We reviewed the most recent literature and guidelines in this field and organized the current recommendations for healthcare professionals caring for critically ill organ transplant recipients. RECENT FINDINGS The incidence of multidrug-resistant organisms is increasing. Multidrug-resistant Gram-negative bacteria comprise about 14% of organisms. Vancomycin-resistant enterococci bloodstream infections are also on the rise, as 20.5% of nosocomial enterococci are now vancomycin-resistant, changing empiric antibiotic selection. Fluconazole-resistant Candida species comprise up to 46% of cases of candidemia in hospitalized patients. Consequently, new guidelines recommend primary use of echinocandins in patients with candidemia who have moderate-to-severe disease. Finally, the incidence of emergence of ganciclovir-resistant cytomegalovirus infection in patients is 5-12%, requiring early recognition and change to alternative regimens in the case of poor response to therapy. SUMMARY Bloodstream infections are a major cause of mortality and morbidity in solid organ transplantation. Mortality as high as 24% and 50% have been reported with sepsis and septic shock respectively. As such, bloodstream infections should be diagnosed rapidly and intravenous antibiotics should be started immediately. Appropriate resuscitation should be initiated and the number and/or dose of immunosuppressive drugs should be reduced. Proper source control must also be achieved with radiologic drainage or surgical intervention as appropriate. Initial antibiotic treatment of these patients should cover both Gram-positive organisms, especially in the presence of intravascular catheters, and Gram-negative bacteria. Echinocandins like caspofungin should also be considered especially in critically ill patients, particularly if a patient has been on total parenteral nutrition or broad-spectrum antibiotics.
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Affiliation(s)
- Aaron Kaviani
- Organ Transplant Center, Department of Surgery, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242 USA
| | - Dilek Ince
- Department of Internal Medicine, Division of Infectious Diseases, University of Iowa Hospitals & Clinics, Iowa City, USA
| | - David A. Axelrod
- Organ Transplant Center, Department of Surgery, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242 USA
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4
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L'Huillier AG, Ferreira VH, Ku T, Bahinskaya I, Kumar D, Humar A. Improving our mechanistic understanding of the indirect effects of CMV infection in transplant recipients. Am J Transplant 2019; 19:2495-2504. [PMID: 30916879 DOI: 10.1111/ajt.15371] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/17/2019] [Accepted: 03/18/2019] [Indexed: 01/25/2023]
Abstract
Cytomegalovirus (CMV) is an immunomodulatory virus that indirectly increases the risk for bacterial, fungal, and viral infections. However, the pathogenesis of this phenomenon is poorly understood. We determined whether inflammatory responses to different Toll-like receptor (TLR) ligands are blunted during CMV infection in solid-organ transplant (SOT) patients. Peripheral blood mononuclear cells from 38 SOT patients with and without CMV were incubated in the presence of various viral, fungal, and bacterial TLR ligands. Cytokines were measured in the supernatant by multiplex enzyme-linked immunosorbent assay. Patients had blunted cytokine responses to bacterial, fungal, and viral ligands during CMV infection when compared to the absence of CMV infection. This was independent of viral load, clinical presentation of CMV infection or immunosuppression, supporting the clinical observation in SOT recipients that CMV infection increases susceptibility to bacterial, fungal, and other viral infections. Moreover, in the absence of CMV infection, patients with subsequent CMV infection had lower cytokines in response to TLR ligands compared to those without subsequent CMV infection, suggesting that inherent differences in patients not directly related to CMV also contribute to this increased susceptibility. In summary, these data provide novel ex vivo evidence to support indirect effects of CMV.
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Affiliation(s)
- Arnaud G L'Huillier
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Victor H Ferreira
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Terrance Ku
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Ilona Bahinskaya
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Deepali Kumar
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Atul Humar
- Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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5
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Abbo LM, Grossi PA. Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13589. [PMID: 31077619 DOI: 10.1111/ctr.13589] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Accepted: 05/06/2019] [Indexed: 02/06/2023]
Abstract
These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post-operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%-53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end-stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug-resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri-operative antibiotic prophylaxis to minimize post-operative SSIs.
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Affiliation(s)
- Lilian M Abbo
- Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine and Jackson Health System, Miami, Florida
| | - Paolo Antonio Grossi
- Infectious Diseases Section, Department of Medicine and Surgery, University of Insubria, Varese, Italy
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6
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Perioperative Antibiotic Prophylaxis to Prevent Surgical Site Infections in Solid Organ Transplantation. Transplantation 2018; 102:21-34. [DOI: 10.1097/tp.0000000000001848] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Salim A, Brown C, Inaba K, Martin MJ. Care of the Patient with Liver Failure Requiring Transplantation. SURGICAL CRITICAL CARE THERAPY 2018. [PMCID: PMC7123773 DOI: 10.1007/978-3-319-71712-8_55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Patients undergo liver transplantation to address chronic liver failure, acute fulminant liver failure, or primary liver cancer. Depending on acuity, patients with decompensated chronic or acute fulminant liver failure generally require preoperative intensive care unit admission to manage organ dysfunction. Those with chronic liver failure are allocated an organ based on waiting list position determined by their local organ procurement organization (OPO). This position is dependent upon blood type and Model for End- Stage Liver Disease (MELD) score. These patients thus are critically ill and require preoperative ICU monitoring and care. Patients with hepatocellular carcinoma (HCC) who require liver transplantation are given a MELD exception and rarely require preoperative ICU care. The patient’s ability to undergo liver transplant in the setting of HCC is determined by the Milan criteria or the University of California, San Francisco (UCSF) criteria.
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Affiliation(s)
- Ali Salim
- Brigham and Womens’s Hospital, Harvard Medical School, Boston, Massachusetts USA
| | - Carlos Brown
- Dell Medical School, University of Texas at Austin, Austin, Texas USA
| | - Kenji Inaba
- Division of Trauma Surgery, Rm C5L100, University of Southern California, Los Angeles, California USA
| | - Matthew J. Martin
- Trauma and Emergency Surgery Service, Legacy Emanuel Medical Center, Portland, Oregon USA
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8
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Vinuesa V, Solano C, Giménez E, Piñana JL, Boluda JCH, Amat P, Navarro D. Lack of evidence for a reciprocal interaction between bacterial and cytomegalovirus infection in the allogeneic stem cell transplantation setting. Transpl Int 2016; 29:1196-1204. [DOI: 10.1111/tri.12831] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 06/28/2016] [Accepted: 08/02/2016] [Indexed: 01/15/2023]
Affiliation(s)
- Víctor Vinuesa
- Microbiology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
| | - Carlos Solano
- Hematology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
- Department of Medicine; School of Medicine; University of Valencia; Valencia Spain
| | - Estela Giménez
- Microbiology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
| | - José L. Piñana
- Hematology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
| | | | - Paula Amat
- Hematology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
| | - David Navarro
- Microbiology Service; Fundación INCLIVA; Hospital Clínico Universitario; Valencia Spain
- Department of Microbiology; School of Medicine; University of Valencia; Valencia Spain
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9
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Impact of Cytomegalovirus Infection on Severe Hepatitis C Recurrence in Patients Undergoing Liver Transplantation. Transplantation 2016; 100:593-9. [PMID: 26371595 DOI: 10.1097/tp.0000000000000912] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation. METHODS An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence. RESULTS Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence. CONCLUSIONS Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease.
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10
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Abstract
Antiviral drug discovery has produced a series of drugs active against herpesviruses in vitro. Several of these are now licensed and/or have been used in clinical practice. This article reviews the mechanisms of action of acyclovir, ganciclovir, penciclovir, sorivudine and foscarnet, the development of resistance to these drugs and their pharmacokinetic and cellular toxicities. Based upon the natural histories of HSV, VZV and CMV, treatment objectives for each virus are discussed and the performance of each drug matched against these objectives. Overall, it is concluded that the perfect drug for treating herpesviruses does not exist, but that significant progress has been made towards controlling several herpesvirus diseases. It is suggested that further progress will require not just improved drug discovery programmes, but also an understanding of different pathogeneses and an appreciation by practising physicians that antiviral drugs must be given early in the infectious process to achieve the best results.
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Affiliation(s)
- P.D. Griffiths
- Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK
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11
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Abstract
OBJECTIVE To access the incidence of infectious problems after liver transplantation (LT). DESIGN A retrospective, single-center study. MATERIALS AND METHODS Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient's variables, graft variables, surgical data, post-LT clinical data. RESULTS Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 ± 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. CONCLUSION We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors' variables should be considered in future analyses.
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12
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Tsai KC, Danziger-Isakov LA, Banach DB. Cytomegalovirus Infection in Pediatric Solid Organ Transplant Recipients: a Focus on Prevention. Curr Infect Dis Rep 2016; 18:5. [DOI: 10.1007/s11908-015-0511-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Mezochow AK, Henry R, Blumberg EA, Kotton CN. Transfusion transmitted infections in solid organ transplantation. Am J Transplant 2015; 15:547-54. [PMID: 25612502 DOI: 10.1111/ajt.13006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 08/13/2014] [Accepted: 08/28/2014] [Indexed: 01/25/2023]
Abstract
While the risk of infectious disease transmission through blood transfusion has been greatly reduced as a result of improved screening methods, transfusion-transmissible infections remain a concern for transplant recipients, especially those receiving multiple transfusions. Although transfusion and transplant recipients are at risk for similar infections, the current reporting requirements for infections transmitted by transfusions and organ transplantation vary greatly and remain distinctly separate with no communication between reporting systems. This article reviews 23 past reports of transfusion-transmitted infections in organ recipients acquired through transfusions. While cytomegalovirus was a major focus of such reports in the 1980s, more recent reports have focused on West Nile virus transmission. Additionally, this article highlights challenges in determining transfusion-transmitted infection risk in transplant recipients related to the current reporting systems.
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Affiliation(s)
- A K Mezochow
- U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health, Division of Blood and Tissue Safety and Availability, Washington, DC
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Shields RK, Clancy CJ, Minces LR, Shigemura N, Kwak EJ, Silveira FP, Abdel-Massih RC, Bhama JK, Bermudez CA, Pilewski JM, Crespo M, Toyoda Y, Nguyen MH. Epidemiology and outcomes of deep surgical site infections following lung transplantation. Am J Transplant 2013; 13:2137-45. [PMID: 23710593 DOI: 10.1111/ajt.12292] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 03/18/2013] [Accepted: 04/04/2013] [Indexed: 01/25/2023]
Abstract
We conducted a retrospective study of deep surgical site infections (SSIs) among consecutive patients who underwent lung transplantation (LTx) at a single center from 2006 through 2010. Thirty-one patients (5%) developed SSIs at median 25 days after LTx. Empyema was most common (42%), followed by surgical wound infections (29%), mediastinitis (16%), sternal osteomyelitis (6%), and pericarditis (6%). Pathogens included Gram-positive bacteria (41%), Gram-negative bacteria (41%), fungi (10%) and Mycobacterium abscessus, Mycoplasma hominis and Lactobacillus sp. (one each). Twenty-three percent of SSIs were due to pathogens colonizing recipients' native lungs at time of LTx, suggesting surgical seeding as a source. Patient-related independent risk factors for SSIs were diabetes and prior cardiothoracic surgery; procedure-related independent risk factors were LTx from a female donor, prolonged ischemic time and number of perioperative red blood cell transfusions. Mediastinitis and sternal infections were not observed among patients undergoing minimally invasive LTx. SSIs were associated with 35% mortality at 1 year post-LTx. Lengths of stay and mortality in-hospital and at 6 months and 1 year were significantly greater for patients with SSIs other than empyema. In conclusion, deep SSIs were uncommon, but important complications in LTx recipients because of their diverse microbiology and association with increased mortality.
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Affiliation(s)
- R K Shields
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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15
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Katsolis JG, Bosch W, Heckman MG, Diehl NN, Shalev JA, Pungpapong S, Gonwa TA, Hellinger WC. Evaluation of risk factors for cytomegalovirus infection and disease occurring within 1 year of liver transplantation in high-risk patients. Transpl Infect Dis 2013; 15:171-80. [PMID: 23331429 DOI: 10.1111/tid.12050] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2012] [Revised: 08/28/2012] [Accepted: 09/05/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND Recent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high-risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined. METHODS A retrospective cohort study of 227 high-risk first LTR who received primary anti-CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post-transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P-values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant. RESULTS CMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end-stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance. CONCLUSION Our results suggest that interventions designed to prevent CMV infection and disease should be applied to all high-risk LTR until more definitive predictors of these complications are identified.
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Affiliation(s)
- J G Katsolis
- Division of Infectious Diseases, Mayo Clinic Florida, Jacksonville, Florida 32224, USA
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16
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Gredmark-Russ S, Söderberg-Nauclér C. Dendritic cell biology in human cytomegalovirus infection and the clinical consequences for host immunity and pathology. Virulence 2012; 3:621-34. [PMID: 23076329 PMCID: PMC3545944 DOI: 10.4161/viru.22239] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Human cytomegalovirus (HCMV), a member of the herpesvirus family, establishes life-long persistence and latency after primary infection and can be reactivated later in life. In immunosuppressed patients, it is an important pathogen that can cause severe disease. HCMV is also thought to play a causative role in inflammatory diseases and cancer. The virus can infect different immune cells, including dendritic cells (DCs) and can take advantage of host immune functions to avoid immune recognition. These characteristics have sparked major interest in understanding HCMV and its interaction with immune cells and their relevance to disease pathogenesis. In this review, we focus on the complex host-pathogen relationship between HCMV and DCs, including the persistence of the virus in these cells, their function in the immune response to HCMV infection and the potential clinical consequences of HCMV infection in DCs.
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Affiliation(s)
- Sara Gredmark-Russ
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
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17
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Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case. Surg Today 2012; 43:424-8. [PMID: 22797959 DOI: 10.1007/s00595-012-0209-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2011] [Accepted: 12/15/2011] [Indexed: 02/07/2023]
Abstract
Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.
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Bansal N, Arora A, Kumaran V, Mehta N, Varma V, Sharma P, Tyagi P, Sachdeva M, Kumar A. Atypical presentation of cytomegalovirus infection in a liver transplant patient. J Clin Exp Hepatol 2011; 1:207-9. [PMID: 25755388 PMCID: PMC3940243 DOI: 10.1016/s0973-6883(11)60236-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Accepted: 11/29/2011] [Indexed: 12/12/2022] Open
Abstract
Cytomegalovirus (CMV) is the most common viral infection in solid organ transplant recipients. Symptomatic infection usually presents with fever, pneumonia, colitis, or cytopenia. We describe a case of symptomatic CMV infection in a liver transplant recipient presenting with atypical symptoms of only persistent nausea and vomiting, in the absence of classical symptoms and signs; thus, highlighting the importance of high index of suspicion of CMV in immunocompromised patients, keeping in mind the high morbidity and mortality associated with this disease.
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Key Words
- ALT, alanine aminotransferase
- ANA, anti-nuclear antibody
- ASMA, antibody smooth muscle antigen
- AST, aspartate aminotransferase
- Atypical presentation
- CMV, cytomegalovirus
- EBV, Epstein-Barr virus
- HBsAg, hepatitis B surface antigen
- HEV, hepatitis E virus
- INR, international normalized ratio
- anti-HBc, antibody-hepatitis B core
- anti-HCV, antibody-hepatitis C virus
- anti-LKM, antibody-liver–kidney-microsomal antigen
- cytomegalovirus
- i.v., intravenous
- immunosuppressed
- liver transplant
- transplantation
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Affiliation(s)
- Naresh Bansal
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Vinay Kumaran
- Department of Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Naimish Mehta
- Department of Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Vibha Varma
- Department of Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
| | - Praveen Sharma
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Pankaj Tyagi
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Munish Sachdeva
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India
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Hellinger WC, Heckman MG, Crook JE, Taner CB, Willingham DL, Diehl NN, Zubair AC, Shalev JA, Nguyen JH. Association of surgeon with surgical site infection after liver transplantation. Am J Transplant 2011; 11:1877-84. [PMID: 21827617 DOI: 10.1111/j.1600-6143.2011.03644.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Surgical site infection (SSI) after liver transplantation has been associated with increased risk of allograft loss and death. Identification of modifiable risk factors for these infections is imperative. To our knowledge, intraoperative practices associated with transplant surgeons have not been assessed as a risk factor. A retrospective cohort study of risk factors for SSI after 1036 first liver transplantations completed by seven surgeons at a single center between 2003 and 2008 was undertaken. Cox proportional hazards models were used to evaluate the association between surgeons and SSIs. SSIs were identified in 166 of 1036 patients (16%). Single variable analysis showed strong evidence of an association between surgeon and SSI (p = 0.0007); the estimated cumulative incidence of SSI ranged from 7% to 24%. This result was consistent in multivariable analysis adjusting for potentially confounding variables (p = 0.002). The occurrence of organ-space or deep SSI varied significantly among surgeons in both single variable analysis (p = 0.005) and multivariable analysis (p = 0.006). These findings provide evidence that differences in the surgical practices of individual surgeons are associated with risk for SSI after liver transplantation. Identification of specific surgical practices associated with risk of SSI is warranted.
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Affiliation(s)
- W C Hellinger
- Division of Infectious Diseases Biostatistics Unit Division of Transplant Surgery, Mayo Clinic, Jacksonville, FL, USA.
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20
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Grim SA, Clark NM. Management of Infectious Complications in Solid-Organ Transplant Recipients. Clin Pharmacol Ther 2011; 90:333-42. [DOI: 10.1038/clpt.2011.90] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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21
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Benson AB, Burton JR, Austin GL, Biggins SW, Zimmerman MA, Kam I, Mandell S, Silliman CC, Rosen H, Moss M. Differential effects of plasma and red blood cell transfusions on acute lung injury and infection risk following liver transplantation. Liver Transpl 2011; 17:149-58. [PMID: 21280188 PMCID: PMC3399914 DOI: 10.1002/lt.22212] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Patients with chronic liver disease have an increased risk of developing transfusion-related acute lung injury (TRALI) from plasma-containing blood products. Similarly, red blood cell transfusions have been associated with postoperative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive large amounts of cellular and plasma-containing blood components, but it is presently unclear which blood components are associated with these postoperative complications. A retrospective cohort study of 525 consecutive liver transplant patients revealed a perioperative TRALI rate of 1.3% (7/525, 95% confidence interval = 0.6%-2.7%), which was associated with increases in the hospital mortality rate [28.6% (2/7) versus 2.9% (15/518), P = 0.02] and the intensive care unit length of stay [2 (1-11 days) versus 0 days (0-2 days), P = 0.03]. Only high-plasma-containing blood products (plasma and platelets) were associated with the development of TRALI. Seventy-four of 525 patients (14.1%) developed a postoperative infection, and this was also associated with increased in-hospital mortality [10.8% (8/74) versus 2.0% (9/451), P < 0.01] and a prolonged length of stay. Multivariate logistic regression determined that the number of transfused red blood cell units (adjusted odds ratio = 1.08, 95% confidence interval = 1.02-1.14, P < 0.01), the presence of perioperative renal dysfunction, and reoperation were significantly associated with postoperative infection. In conclusion, patients undergoing liver transplantation have a high risk of developing postoperative complications from blood transfusion. Plasma-containing blood products were associated with the development of TRALI, whereas red blood cells were associated with the development of postoperative infections in a dose-dependent manner.
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Affiliation(s)
- Alexander B. Benson
- Division of Pulmonary Sciences and Critical Care, University of Colorado, Aurora, CO
| | - James R. Burton
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| | - Gregory L. Austin
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| | - Scott W. Biggins
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| | | | - Igal Kam
- Department of Transplant Surgery, University of Colorado, Aurora, CO
| | - Susan Mandell
- Department of Anesthesia, University of Colorado, Aurora, CO
| | | | - Hugo Rosen
- Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO
| | - Marc Moss
- Division of Pulmonary Sciences and Critical Care, University of Colorado, Aurora, CO
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22
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Chow JK, Werner BG, Ruthazer R, Snydman DR. Increased serum iron levels and infectious complications after liver transplantation. Clin Infect Dis 2010; 51:e16-23. [PMID: 20578876 DOI: 10.1086/654802] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Elevated serum iron levels have been associated with infectious outcomes in various patient populations but, to our knowledge, have never been studied after liver transplantation. METHODS The relationship between serum iron levels and infectious outcomes after liver transplantation was evaluated in a nested case-control study using prospectively collected data and serum samples. Unadjusted and adjusted hazard ratios were calculated for each iron marker predictor variable (iron level, unsaturated iron-binding capacity, total iron-binding capacity, transferrin saturation, and ferritin level) and time to development of each of 6 outcomes (cytomegalovirus [CMV] disease, invasive fungal infection, bacteremia, invasive fungal infection or bacteremia, any infection, and 1-year mortality rate). RESULTS Serum measurements (n = 109) corresponding to increased levels of serum iron were independently associated with an increased risk of any infection and death. After adjusting for the number of red blood cell transfusions, donor CMV-seropositive status, and fungal colonization, ferritin level was independently associated with the development of any infection (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14). After adjusting for the number of red blood cell transfusions, development of CMV disease, and administration of intravenous steroids for treatment of rejection, ferritin level was also was independently associated with death (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18). Similar results were found for unsaturated iron binding capacity for the same 2 outcomes. CONCLUSIONS A better understanding of iron metabolism and its relationship to infection could help guide future infection prognosis, prevention, and management efforts in this high-risk population.
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Affiliation(s)
- Jennifer K Chow
- Division of Geographic Medicine and Infectious Disease, Tufts University School of Medicine, Boston, MA, USA.
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23
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Influence of alemtuzumab on the intestinal Paneth cells and microflora in macaques. Clin Immunol 2010; 136:375-86. [PMID: 20605528 DOI: 10.1016/j.clim.2010.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2009] [Revised: 05/10/2010] [Accepted: 05/10/2010] [Indexed: 01/09/2023]
Abstract
Alemtuzumab has been recently introduced for induction therapy in organ transplantation. However, the pathogenesis and molecular mechanism of the impact of such induction therapy on bacterial infections remain to be clarified. We found the alterations of Paneth cells including abnormal Paneth cell granules and expression of lysozyme and defensin 5 in response to lymphocyte depletion by alemtuzumab. Lymphocyte depletion resulted in decreased expression of TNF-alpha, IFN-gamma, IL-10 and TGF-beta in the intestine. The diversity of gut bacteria varied significantly between different times of alemtuzumab treatment. Abnormal expression of granule peptides might result in impairment of host gut microflora. The alterations in bacterial microflora had almost reversed 56days after alemtuzumab treatment, which was consistent with our results that Paneth cells were recovered to secrete antimicrobial peptides to govern gut microflora. These findings indicated the associations between changes of Paneth cell function and gut microflora and supported the important role of Paneth cells to barrier impairment with the use of alemtuzumab in organ transplantation.
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24
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Kimura T, Lauro A, Cescon M, Zanfi C, Dazzi A, Ercolani G, Grazi GL, Vivarelli M, Ravaioli M, Del Gaudio M, Cucchetti A, Zanello M, LaBarba G, Pironi L, Lazzarotto T, Pinna AD. Impact of induction therapy on bacterial infections and long-term outcome in adult intestinal and multivisceral transplantation: a comparison of two different induction protocols: daclizumab vs. alemtuzumab. Clin Transplant 2009; 23:420-425. [PMID: 19537304 DOI: 10.1111/j.1399-0012.2008.00922.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Induction therapy with daclizumab or alemtuzumab has been recently introduced for intestinal transplantation; however, the impact of such induction therapy on bacterial infections remains to be clarified. The purpose of this study was to evaluate the impact of induction therapy on the incidence of bacterial infections and long-term patient survival. PATIENTS AND METHODS Over the past seven yr, we performed 39 intestinal (ITx) and multivisceral (MTVx) transplants in 38 adult patients. In the early period, daclizumab was used for induction, and tacrolimus and steroids were administered for maintenance [daclizumab and tacrolimus (DT) group; n = 11]. From 2002, we used alemtuzumab for induction, with low-dose tacrolimus maintenance [alemtuzumab and tacrolimus (AT) group; n = 23]. The incidence of bacterial infections and patient outcome were compared between the two groups. RESULTS There were no significant differences in recipient and donor demographics, procedure (ITx vs. MTVx), and cold and warm ischemic time between the two groups. Within 30 d after ITx, bacterial infections were observed in seven patients (64%) in the DT and in 14 patients (64%) in the AT group. Between 30 and 180 d after ITx, a total of 17 episodes of bacterial infections were observed in the DT and 26 episodes in the AT group. Three patients in the DT and eight in the AT group died, and all of the deaths were related to infectious complications except one each in DT and AT. CONCLUSION There was no difference in incidence of bacterial infections and long-term patient survival between the two groups.
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Affiliation(s)
- Takuya Kimura
- Division of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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25
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Seeking beyond rejection: an update on the differential diagnosis and a practical approach to liver allograft biopsy interpretation. Adv Anat Pathol 2009; 16:97-117. [PMID: 19550371 DOI: 10.1097/pap.0b013e31819946aa] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Pathologic evaluation of liver allograft biopsies plays an integral role in the management of patients after liver transplantation. This review summarizes the clinical context and classical histology of different types of allograft rejection and also the common entities that enter the differential diagnosis of allograft rejection, and provides practical approaches to liver allograft biopsy interpretation. In addition, some of the new developments in the field of liver transplant pathology are updated. The purpose of this review is to provide guidance for pathologists interpreting liver allograft biopsies, particularly those interested in developing expertise in the field of liver transplant pathology.
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26
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Snyder JJ, Israni AK, Peng Y, Zhang L, Simon TA, Kasiske BL. Rates of first infection following kidney transplant in the United States. Kidney Int 2008; 75:317-26. [PMID: 19020531 DOI: 10.1038/ki.2008.580] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
We studied the incidence, trends and clinical correlates of infections following kidney transplantation in the United States Renal Data System over the years 1995-2003 in 46,471 adults with Medicare primary coverage at the time of their first kidney transplant. The incidence of most infections has declined only slightly since 1995 but infection with cytomegalovirus significantly declined while that with hepatitis C significantly increased. Relative frequencies of different types of infections (bacterial, viral, fungal and parasitic) were relatively constant, both during early and late periods following transplant. Using the Cox proportional hazards analysis we found that the clinical correlates for post-transplant bacterial and viral infections included older age, female gender, diabetes as the cause of end-stage renal disease, deceased (vs. living) donor source, time on dialysis before transplant, hepatitis B and C viral pre-transplant serologic status and pre-transplant donor-recipient cytomegalovirus serology. Our study shows that despite identifiable risk factors, the incidence of most post-transplant infections has changed little since 1995.
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Affiliation(s)
- Jon J Snyder
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota 55404, USA.
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27
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Snydman D. Editorial Commentary:Persistent Clinical Impact of Cytomegalovirus in Organ Transplantation. Clin Infect Dis 2008; 47:883-4. [DOI: 10.1086/591533] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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28
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Egli A, Bergamin O, Müllhaupt B, Seebach J, Mueller N, Hirsch H. Cytomegalovirus-associated chorioretinitis after liver transplantation: case report and review of the literature. Transpl Infect Dis 2008; 10:27-43. [DOI: 10.1111/j.1399-3062.2007.00285.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Souza MVD, Barth AL, Álvares-da-Silva MR, Machado ARL. Infections after liver transplantation in adults: data from a university hospital in southern Brazil (1996-2000). ARQUIVOS DE GASTROENTEROLOGIA 2007; 44:128-32. [DOI: 10.1590/s0004-28032007000200008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2005] [Accepted: 12/05/2006] [Indexed: 11/22/2022]
Abstract
BACKGROUND: Infections after liver transplantations are the most important cause of morbi-mortality. In this study, we assessed the main characteristics of these infections in a southern Brazilian university hospital. METHODS: We conducted a retrospective cohort with 55 patients who underwent orthotopic liver transplantation between 1996 and 2000 in the "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, to characterize the infections that occurred in the group. RESULTS: One or more infections (average 2.10) were diagnosed in 47 patients, especially during the first month after transplantation. The most common were bacteremia, intra-abdominal infections and pneumonia, predominantly with bacteria, especially Staphylococcus sp (and particularly S. aureus) and E. coli. The mortality rate attributed to infections was high: 17 cases of all deaths (total 27 deaths). Significant risk factors for infections included reoperation, diabetes, biliary stenosis and higher Child-Pugh scores. CONCLUSION: Infections remain a severe threat in liver transplant patients, and special efforts should be made to prevent and manage them correctly.
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Saito T, Egawa H, Kudo T, Takakura S, Fujihara N, Iinuma Y, Ichiyama S. Pre-transplant risk factors predicting post-transplant cytomegalovirus infection in liver transplant recipients. Transpl Int 2007; 20:419-24. [PMID: 17313448 DOI: 10.1111/j.1432-2277.2007.00459.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cytomegalovirus (CMV) infection causes significant morbidity and mortality among transplant recipients. Although it is still not clear if a preemptive strategy is superior to a prophylactic strategy, many transplant programs elect for preemptive treatment for post-transplant CMV infection. In order to improve the preemptive strategy, we analyzed a series of liver recipients by means of quantitative real-time polymerase chain reaction (PCR). Ninety-one liver transplant recipients were monitored by real-time PCR for CMV, and the results were analyzed in terms of preoperative conditions. Multivariate analysis revealed fulminant hepatic failure as an underlying disease (odds ratio, 6.8; 95% CI, 1.2-39.2), while an ABO-incompatible graft (odds ratio, 5.0; 95% CI, 1.3-19.1), and a serological combination of the donor (D) being positive with the recipient (R) being negative for CMV (D+/R-) (odds ratio, 5.8; 95% CI, 1.3-26.0) were independently associated with the development of significant CMV infection. Patients with risk factors had higher peak CMV DNA concentrations than those without, and developed CMV infections faster (P = 0.0002). Screening of recipients according to risk factors and PCR monitoring may result in an optimization of the preemptive strategy.
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Affiliation(s)
- Takashi Saito
- Department of Clinical Laboratory Medicine, Kyoto University Hospital, Shogoin, Kyoto, Japan.
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31
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Hellinger WC, Bonatti H, Machicao VI, Yao JD, Brumble LM, Alvarez S, Weigand SD, Dickson RC, Harnois DM, Spivey JR, Stapelfeldt WH, Hughes CB, Nguyen JH, Steers JL. Effect of antiviral chemoprophylaxis on adverse clinical outcomes associated with cytomegalovirus after liver transplantation. Mayo Clin Proc 2006; 81:1029-33. [PMID: 16901025 DOI: 10.4065/81.8.1029] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To assess t he association be tweencytomegalovirus (CMV) serology of donor and recipient and adverse outcomes afterliver transplantation in the era of effective antiviral chemoprophylaxis. PATIENTS AND METHODS We performed a retrospective cohort study of 193 consecutive patients undergoing their first liver transplantation between February 1998 and July 2000 with targeted and preemptive ganciclovir chemoprophylaxis. Patients were divided into 4 groups by CMV serology of donor and recipient: donor-/recipient-; donor-/recipient+; donor+/recipient+; and donor+/recipient-. Survival to the end points of retransplantation, death, or survival to 1 year after transplantation (whichever occurred first) was assessed. Rates of bacterial, fungal, and CMV Infection and of CMV disease were recorded and compared. RESULTS No significant differences were observed in the rates of retransplantation, death, or survival to 1 year among the 4 groups of patients. Despite significantly higher rates of CMV infection in the donor+ groups, there were no differences in the rates of bacterial or fungal Infection or of CMV disease. Rejection occurred least frequently in the donor-/recipient- group. CONCLUSION The adverse effects of CMV on outcomes after liver transplantation have been diminished in the era of effective antiviral chemoprophylaxis.
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Affiliation(s)
- Walter C Hellinger
- Division of Infectious Diseases, Mayo Clinic College of Medicine, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.
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32
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Silveira FP, Marcos A, Kwak EJ, Husain S, Shapiro R, Thai N, McCurry KR, Abu-Elmagd K, Paterson DL. Bloodstream infections in organ transplant recipients receiving alemtuzumab: no evidence of occurrence of organisms typically associated with profound T cell depletion. J Infect 2006; 53:241-7. [PMID: 16403576 DOI: 10.1016/j.jinf.2005.11.017] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2005] [Revised: 11/16/2005] [Accepted: 11/17/2005] [Indexed: 11/29/2022]
Abstract
BACKGROUND Alemtuzumab is a humanized monoclonal antibody directed against CD52, a cell surface antigen expressed on B and T lymphocytes, monocytes and NK cells. Its use results in a profound decrease in CD4 positive T lymphocytes. Alemtuzumab is used as induction immunosuppression and therapy for rejection in organ transplant recipients in some centers. We followed a cohort of 449 consecutive transplant recipients who received alemtuzumab to determine the occurrence of bloodstream infections, particularly those previously associated with decrease in CD4 positive T lymphocytes. PATIENTS AND METHODS Fifteen percent (69/449) patients had at least one episode of bloodstream infection. However, no patient had bacteremia with Streptococcus pneumoniae, Listeria monocytogenes, non-typhoidal Salmonella or Mycobacterium avium complex. Fungaemia was rare, occurring in 1.5% of patients. The most common organisms isolated from the blood were Staphylococcus aureus (21 episodes), coagulase negative Staphylococcus (14 episodes), Klebsiella pneumoniae (12 episodes), Enterococcus faecium (11 episodes), Pseudomonas aeruginosa (10 episodes), Enterococcus faecalis (9 episodes) and Escherichia coli (7 episodes). DISCUSSION We conclude that although alemtuzumab use is associated with profound CD4 positive T lymphocyte depletion, alemtuzumab does not seem to be associated with an increased risk of bloodstream infection with pathogens typically seen in other disorders of CD4 cell depletion, such as acquired immunodeficiency syndrome.
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Affiliation(s)
- Fernanda P Silveira
- Division of Infectious Diseases, University of Pittsburgh Medical Center, 3601 Fifth Avenue Suite 3A, Falk Medical Building, Pittsburgh, PA 15213, USA
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Abstract
Cytomegalovirus prevention strategies have been debated for the past decade. This review argues in favour of the prophylaxis strategy. Clinical trials comparing prophylaxis to pre-emptive therapy have, thus far, had insufficient power to differentiate strategies, especially with regard to the indirect effects of CMV. From meta-analyses, prospective trials, observational studies, and case control studies, there is evidence that prophylaxis prevents cytomegalovirus infection and disease, reduces the indirect effects of cytomegalovirus, including organ rejection and transplant associated, all cause mortality as well as opportunistic infection, and even bacteremia as well as post transplant lymphoproliferative disease. Prophylaxis has also been shown to be cost effective. One must recognise that with the current prophylaxis regimens employed for 3 months post-transplantation, late onset cases of cytomegalovirus disease may occur. Cytomegalovirus replication monitoring may be necessary after cessation of prophylaxis, especially in the high risk cytomegalovirus seropositive donor to cytomegalovirus seronegative recipient. Future trials with longer periods of prophylaxis are being undertaken.
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Affiliation(s)
- David R Snydman
- Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, MA, USA.
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34
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Slifkin M, Ruthazer R, Freeman R, Bloom J, Fitzmaurice S, Fairchild R, Angelis M, Cooper J, Barefoot L, Rohrer R, Snydman DR. Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation. Liver Transpl 2005; 11:1597-602. [PMID: 16315314 DOI: 10.1002/lt.20523] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.
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Affiliation(s)
- Michelle Slifkin
- Divisions of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, and Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
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35
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Seehofer D, Rayes N, Neumann UP, Meisel H, Oettle H, Nüssler NC, Jonas S, Langrehr JM, Neuhaus P. Changing impact of cytomegalovirus in liver transplantation - a single centre experience of more than 1000 transplantations without ganciclovir prophylaxis. Transpl Int 2005; 18:941-8. [PMID: 16008744 DOI: 10.1111/j.1432-2277.2005.00162.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
As cytomegalovirus (CMV) disease was a leading cause of death following liver transplantation in earlier reports, general CMV prophylaxis is widely used. We re-evaluated the impact of CMV in a recent time period under balanced immunosuppression and effective CMV diagnostics and therapy. A retrospective analysis of 1200 liver transplantations between 1988 and 2000 was performed comparing the incidence of CMV infection and disease and patient survival rates in two different time periods (before and after availability of the pp65-antigenaemia assay). In addition, risk factors for CMV in the recent time period were analysed. No ganciclovir prophylaxis was administered during the whole study period. The incidence of CMV tissue invasive disease decreased from 9.4% in period I to 2.7% in period II, whereas the incidence of viral syndrome was about 6% in both periods. Especially CMV pneumonia and generalized disease were almost abandoned in period II. Patients with tissue invasive disease, but not with infection or viral syndrome had reduced survival rates in both periods. However, the disease-specific mortality was 10% and 0% respectively. The overall rate of CMV infection in period II was low (25.9%). Risk factors for CMV infection in the univariate analysis were: Initial nonfunction, D+R- seroconstellation, acute liver failure, triple or quadruple immunosuppression, OKT3 or ATG treatment, transfusion of >10 packed red cells, steroid boluses, postoperative mechanical ventilation and retransplantation. In the multivariate analysis only quadruple or triple immunosuppression, OKT3-treatment, transplantation for acute liver failure and initial nonfunction. The incidence of CMV tissue invasive disease as well as the disease-specific mortality has markedly decreased during the last years. Using routine surveillance with the pp65-antigenaemia assay, CMV infection and disease rates compare well to data with long-term ganciclovir prophylaxis. As D+R- patients still more often develop symptomatic disease, pre-emptive therapy could be useful in this patient group.
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Affiliation(s)
- Daniel Seehofer
- Department of General, Visceral and Transplant Surgery, Humboldt University of Berlin, Berlin, Germany.
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Affiliation(s)
- Jørgen Slots
- School of Dentistry, University of Southern California, Los Angeles, CA, USA
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Verma A, Wade JJ, Cheeseman P, Samaroo B, Rela M, Heaton ND, Mieli-Vergani G, Dhawan A. Risk factors for fungal infection in paediatric liver transplant recipients. Pediatr Transplant 2005; 9:220-5. [PMID: 15787797 DOI: 10.1111/j.1399-3046.2005.00295.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Fungal infection (FI) is a major and potentially fatal complication in liver transplantation (LT). Published experience of FI in paediatric LT is limited. We therefore reviewed case records of 79 children, aged between 0.16 and 16 yr, who underwent LT between 1997 and 1998 to document the incidence of, and identify risk factors for, FI. Sixty-eight pre-, peri- and post-LT variables were assessed in relation to FI by univariate and multivariate analyses. The major indications for LT were biliary atresia in 26 (33%) patients, fulminant hepatic failure in 16 (20%) and intrahepatic cholestasis in 11 (14%); eight patients required re-LT. Thirty-two (40.5%) children developed a FI within 1 yr of LT. The median time to FI was 42 days (range 1-342 days). Candida spp. caused 29 (90.7%) FIs; 21 (66%) of these were Candida albicans. Although FI was associated with increased mortality, most patients responded well to antifungal treatment. The variables independently associated with FI were pre-LT fungal colonization and pyrexia and, post-LT, bacterial infection, Epstein-Barr virus (EBV) infection and tacrolimus administration. Identifying risk factors for FI should contribute to the development of strategies for prophylaxis or preemptive therapy.
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Affiliation(s)
- Anita Verma
- Health Protection Agency London, Department of Medical Microbiology, King's College Hospital, London, UK.
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Freeman RB, Paya C, Pescovitz MD, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Heaton N. Risk Factors for Cytomegalovirus Viremia and Disease Developing after Prophylaxis in High-Risk Solid-Organ Transplant Recipients. Transplantation 2004; 78:1765-73. [PMID: 15614149 DOI: 10.1097/01.tp.0000142619.01510.a5] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) D+/R- solid-organ transplant (SOT) recipients carry increased risk of developing CMV disease; however, other risk factors in these patients have not been delineated. METHODS We examined 20 demographic and clinical variables for their association with the development of CMV disease, as defined by an independent endpoint committee (IEC) and also by the investigator (investigator treated [IT]), or CMV viremia within 12 months of transplant in D+/R- transplant recipients who received prophylaxis with valganciclovir or oral ganciclovir for 100 days. RESULTS Recipients with low creatinine clearance (Ccr,<40 mL/min) at screening had a significantly increased hazard of developing IEC-defined CMV disease (hazards ratio [HR]=4.28, confidence interval [CI] 1.69, 10.83). Females were twice as likely (HR=2.19, CI .21, 3.99) to develop IEC-defined CMV disease than males. These variables were associated with an increased risk of IEC-defined CMV disease in time-dependent models. Recipients with blood group A were also more likely to develop IEC-defined CMV disease than those with group O (HR=2.36 CI 1.24, 4.51) in the logistic regression model only. Prophylactic drug, organ type, recipient age, rejection episodes, and maintenance immunosuppression regimen were not associated with IEC-defined CMV disease. Female sex was the only variable associated with the development of CMV viremia (odds ratio [OR]=1.65; CI 1.03, 2.65) and IT CMV disease (OR=1.78; CI 1.08, 2.93). CONCLUSIONS Low Ccr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC- and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.
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Affiliation(s)
- Richard B Freeman
- New England Medical Center of Transplant Surgery, Boston, MA. 2 Mayo Clinic, Rochester, MN 02111, USA.
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Gredmark S, Britt WB, Xie X, Lindbom L, Söderberg-Nauclér C. Human cytomegalovirus induces inhibition of macrophage differentiation by binding to human aminopeptidase N/CD13. THE JOURNAL OF IMMUNOLOGY 2004; 173:4897-907. [PMID: 15470031 DOI: 10.4049/jimmunol.173.8.4897] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Human CMV (HCMV) infection in immunocompromised patients is frequently associated with impaired immunological functions. We have recently found that HCMV inhibits cytokine-induced differentiation of monocytes into macrophages. In this study, we demonstrate that HCMV-induced inhibition of macrophage differentiation was dependent on binding of virus particles to the cell surface molecule CD13/aminopeptidase N, which involved Ca2+ -dependent intracellular signaling pathways. We found that treatment of cells with the CD13-specific mAbs My7 and WM15 inhibited macrophage differentiation, and that My7 and WM15 induced a rise in intracellular Ca2+ in similar ways as HCMV. In contrast, binding of the CD13-specific Ab clone SJ1D1 blocked the ability of HCMV to inhibit macrophage differentiation, and blocked the HCMV-induced intracellular Ca2+ response. In addition, the Ca2+ modulator thapsigargin partially blocked the ability of HCMV to inhibit cellular differentiation. Furthermore, we demonstrate that recombinant viral glycoprotein gB was able to inhibit macrophage differentiation in similar ways as the virus. Thus, these results suggest that binding of HCMV to monocytes induces an intracellular rise of Ca2+, of which one result is a block in the ability of the cells to differentiate into macrophages. These observations suggest an efficient viral strategy to interfere with cellular differentiation pathways, and may also in part explain the generalized immunosuppression that is often observed in HCMV-infected patients.
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Affiliation(s)
- Sara Gredmark
- Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
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Godard B, Gazagne A, Gey A, Baptiste M, Vingert B, Pegaz-Fiornet B, Strompf L, Fridman WH, Glotz D, Tartour E. Optimization of an elispot assay to detect cytomegalovirus-specific CD8+ T lymphocytes. Hum Immunol 2004; 65:1307-18. [PMID: 15556681 DOI: 10.1016/j.humimm.2004.06.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2004] [Revised: 06/08/2004] [Accepted: 06/09/2004] [Indexed: 01/08/2023]
Abstract
Various arguments suggest that CD8+ T lymphocytes play a major role in the control of cytomegalovirus (CMV) infection. The detection of CMV-specific CD8+ T cells may therefore provide additional information about CMV virus detection to predict the risk of development of CMV disease, especially in immunodepressed transplant recipients. We compared and tested various experimental conditions to optimize an enzyme-linked immunospot assay (Elispot) assay for the detection of CMV-specific CD8+ T lymphocytes. The indirect Elispot assay with one six-day in vitro sensitization step was found to be the most sensitive method to detect CMV-specific CD8+ T cells compared to direct Elispot with unfractionated peripheral blood mononuclear cells or purified CD8+ T cells. We showed that low doses of interleukin-2 during the in vitro culture enhanced the sensitivity of this test, and tetramer staining was performed to verify the high efficiency of this in vitro stimulation step. We directly loaded the specific CMV peptide during the Elispot assay and demonstrated that the use of T2 cells did not improve its sensitivity. Elispot for the detection of interferon-gamma appears to be more sensitive and reliable than measurement of tumor necrosis factor alpha or granzyme B. This technique was successfully applied to detect CMV-specific CD8+ T cells in human leukocyte antigen A2 (HLA-A2) and HLA-B7 healthy patients and in one lymphopenic post-transplant patient with positive CMV serology. This highly sensitive test may be a useful tool to assess T-cell immunity directed against CMV in immunodepressed patients.
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Affiliation(s)
- Brigitte Godard
- Unité d'Immunologie Biologique, Hopital Européen Georges Pompidou, AP-HP, Paris, France
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Munoz-Price LS, Slifkin M, Ruthazer R, Poutsiaka DD, Hadley S, Freeman R, Rohrer R, Angelis M, Cooper J, Fairchild R, Barefoot L, Bloom J, Fitzmaurice S, Snydman DR. The Clinical Impact of Ganciclovir Prophylaxis on the Occurrence of Bacteremia in Orthotopic Liver Transplant Recipients. Clin Infect Dis 2004; 39:1293-9. [PMID: 15494905 DOI: 10.1086/425002] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2004] [Accepted: 06/15/2004] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection or receipt of a CMV-seropositive donor liver has been shown to be an independent predictor of bacteremia in orthotopic liver transplant (OLT) recipients. However, prevention of CMV infection through use of intense CMV prophylaxis has not been examined to assess the impact on bacteremia in liver transplant recipients. METHODS We analyzed the impact of CMV prophylaxis on rates of bacteremia by examining 192 consecutive OLT recipients during a 2-year follow-up period. RESULTS There were 29 episodes of bacteremia. Univariate analysis of risk factors for bacteremia showed that invasive fungal disease, initial anti-lymphocyte immunosuppression, treatment for rejection, and use of solumedrol were significantly associated with increased risk. Receipt of >or=14 days of ganciclovir prophylaxis (hazard ratio [HR], 0.40; 95% CI [confidence interval], 0.18-0.87; P=.02), end-to-end biliary anastomosis, and receipt of <10 units of red blood cells (RBCs) were significantly associated with a decreased risk. Three-variable analysis controlling for end-to-end anastomosis and use of <10 units of RBCs, showed that use of >or=14 days of ganciclovir was still associated with a reduced risk of bacteremia (HR, 0.44; 95% CI, 0.20-0.98; P=.0437). CONCLUSIONS Among factors associated with bacteremia, use of prophylactic ganciclovir is independently associated with a significant reduction of bacteremia in OLT recipients.
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Affiliation(s)
- L Silvia Munoz-Price
- Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University, Boston, Massachusetts 02111, USA
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Gredmark S, Tilburgs T, Söderberg-Nauclér C. Human cytomegalovirus inhibits cytokine-induced macrophage differentiation. J Virol 2004; 78:10378-89. [PMID: 15367604 PMCID: PMC516431 DOI: 10.1128/jvi.78.19.10378-10389.2004] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Human cytomegalovirus (HCMV) infection in immunocompromised patients is associated with impaired immunological function. Blood monocytes, which differentiate into macrophage effector cells, are of central importance for immune reactivity. Here, we demonstrate that HCMV transiently blocks cytokine-induced differentiation of monocytes into functionally active phagocytic macrophages. In HCMV-treated cultures, the cells had classical macrophage markers but lacked the classical morphological appearance of macrophages and had impairments in migration and phagocytosis. Even at very low multiplicities of infection, macrophage differentiation was almost completely inhibited. The inhibition appeared to be mediated by a soluble factor released upon viral treatment of monocytes. Human immunodeficiency virus or measles virus had no such effects. These findings suggest that HCMV impairs immune function by blocking certain aspects of cytokine-induced differentiation of monocytes and demonstrate an efficient pathway for this virus to evade immune recognition that may have clinical implications for the generalized immunosuppression often observed in HCMV-infected patients.
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Affiliation(s)
- Sara Gredmark
- Karolinska Systems Biomedicine Center, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden
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Hafiz MM, Poggioli R, Caulfield A, Messinger S, Geiger MC, Baidal DA, Froud T, Ferreira JV, Tzakis AG, Ricordi C, Alejandro R. Cytomegalovirus prevalence and transmission after islet allograft transplant in patients with type 1 diabetes mellitus. Am J Transplant 2004; 4:1697-702. [PMID: 15367227 DOI: 10.1111/j.1600-6143.2004.00557.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch.
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Affiliation(s)
- Muhammad M Hafiz
- Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA
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Abstract
AIM Human cytomegalovirus (HCMV), a herpesvirus, is discussed in this review as it relates to destructive periodontal disease in humans. RESULTS HCMV genomic sequences, detected by polymerase chain reaction identification, occur with elevated frequency in severe adult periodontitis, localized and generalized aggressive (juvenile) periodontitis, Papillon-Lefèvre syndrome periodontitis, acute necrotizing ulcerative gingivitis, and periodontal abscesses. DISCUSSION Herpesviruses establish lifelong persistent infections. HCMV infection involves an asymptomatic latent phase interrupted by periods of recrudescence where viral replication and possibly clinical disease become manifest. HCMV reactivation is triggered by a number of immunosuppressive factors, some of which have been shown also to be risk factors/indicators of periodontitis. HCMV periodontal infection may cause release of tissue-destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathologic events. CONCLUSIONS A growing body of data supports the concept that HCMV contributes to severe types of periodontal disease. HCMV infection of the periodontium may alter the immune control of resident microorganisms and be important in a multistage pathogenesis of periodontitis involving viral activation, periodontopathic bacteria, and host immune responses. Understanding the significance of HCMV and other herpesviruses in the development of periodontal disease may have important therapeutic implications. Vaccines against HCMV, which are in various stages of development, need to be evaluated for their ability to decrease the incidence of destructive periodontal disease.
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Affiliation(s)
- J Slots
- University of Southern California, School of Dentistry, Los Angeles, CA 90089-0641, USA.
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Leong RWL, Smith DW, Garas G, Beaman JM, Mitchell AW, Heath DI, House AK, Jeffrey GP. Aciclovir or ganciclovir universal prophylaxis of cytomegalovirus infection in liver transplantation: an economic analysis. Intern Med J 2004; 34:410-5. [PMID: 15271175 DOI: 10.1111/j.1445-5994.2004.00567.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) following orthotopic liver transplantation can result in significant morbidity and mortality. Prophylaxis with oral aciclovir (ACV) or ganciclovir (GCV) for all transplant recipients (universal prophylaxis) may be beneficial, but which agent is more cost-effective is unknown. METHODS A single centre, retrospective study of all patients who had OLT at the Western Australian Liver Transplantation Service was performed. Patients received ACV from 1992 to 1998, and GCV from 1999 to 2001. A comparative cost-effectiveness analysis for the two groups was performed based on the mean total cost of the number of cases of CMV infection and disease as the clinical end-point. RESULTS The ACV group comprised of 55 patients and there were 24 in the GCV group. The incidence of CMV disease was 7% and 4% for the ACV and GCV groups, respectively (P > 0.05). For CMV infection it was 16% and 8%, respectively (P > 0.05). GCV prevented more cases of CMV infection and disease than ACV but at an incremental cost of dollars A20,000 (dollars US10,172) per case prevented. Overall, ACV was more cost-effective than GCV by dollars A2200 (dollars US1119) per person. The cost benefit of ACV was derived principally through a reduced pharmaceutical cost. Both agents were well tolerated without development of antiviral resistance. CONCLUSIONS Universal prophylaxis of CMV infection-following liver transplantation with aciclovir is more cost-effective than with ganciclovir.
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Affiliation(s)
- R W L Leong
- Western Australian Liver Transplantation Service, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
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Abstract
Cytomegalovirus (CMV) remains one of the most frequent viral infections and the most common cause of death after liver transplantation (LT). Chronic allograft liver rejection remains the major obstacle to long-term allograft survival and CMV infection is one of the suggested risk factors for chronic allograft rejection. The precise relationship between cytomegalovirus and chronic rejection remains uncertain. This review addresses the morbidity of cytomegalovirus infection and the risk factors associated with it, the relationship between cytomegalovirus and chronic allograft liver rejection and the potential mechanisms of it.
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Affiliation(s)
- Liang-Hui Gao
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University, PO Box 4193, Hubin Campus, 353 Yan'an Road, Hangzhou 310031, Zhejiang Province, China.
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Abstract
PURPOSE This study presents a series of organ transplant patients who developed problems that affected their upper extremities, related to the organ transplant operation itself, to the patient's underlying systemic disease, to long-term immunosuppression, or to subsequent hand injury after the organ transplant surgery. METHODS A retrospective chart review of 40 organ transplant patients with upper extremity problems at 3 major organ transplant centers was performed. RESULTS Six general problems were identified that affected the hand and upper extremity in these transplant patients: inflammatory conditions (16), nerve compression syndromes (18), infections (6), neoplasms (6), vascular problems (4), and trauma (14). Thirty-eight patients had 72 separate hand procedures. No problems were encountered with postoperative infections, and skin and bony healing occurred uneventfully. CONCLUSIONS Organ transplant patients are prone to developing atypical infections, skin malignancies, ischemia, and various nerve compression syndromes that affect the hand. These patients with upper-extremity problems should be treated in a manner similar to any patient without prior organ transplant.
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Affiliation(s)
- Neil F Jones
- Department of Orthopedic Surgery, Division of Plastic and Reconstructive Surgery, University of California-Los Angeles, 200 UCLA Medical Plaza #140, Los Angeles, CA 90095, USA
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Gredmark S, Söderberg-Nauclér C. Human cytomegalovirus inhibits differentiation of monocytes into dendritic cells with the consequence of depressed immunological functions. J Virol 2003; 77:10943-56. [PMID: 14512544 PMCID: PMC224957 DOI: 10.1128/jvi.77.20.10943-10956.2003] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Human cytomegalovirus (HCMV) infections in immunocompromised patients are associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity and are believed to carry latent HCMV. We demonstrate here that HCMV infection of monocytes results in a block in the cytokine-induced differentiation of monocytes into functionally active CD1a-positive dendritic cells, which exhibited severely depressed immunological functions in vitro. The HCMV-infected cells exhibited a significantly reduced ability to endocytose fluorescein isothiocyanate-labeled dextran particles as well as a more than 90% reduced ability to migrate in response to the chemoattractant factors RANTES, MIP-1alpha, and MIP-3beta. Interestingly, HCMV-infected cells expressed high levels of the costimulatory molecule CD86, in contrast to the low levels of expression that was observed on uninfected monocytes and uninfected immature dendritic cells. Furthermore, HCMV-infected CD1a-negative cells were unable to induce a T-cell response. Thus, these observations suggest that HCMV infection of monocytes in vitro blocks cytokine-induced dendritic cell differentiation, and since dendritic cells play a central role in initiating immune responses, these findings suggest a powerful tactic to avoid immune recognition and to blunt the immune response at early phases of infection.
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Singhal S, Khan OA, Bramble RA, Mutimer DJ. Cytomegalovirus disease following liver transplantation: an analysis of prophylaxis strategies. J Infect 2003; 47:104-9. [PMID: 12860142 DOI: 10.1016/s0163-4453(03)00018-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality following liver transplantation. Though oral ganciclovir may be used as a prophylactic agent, there is some debate as to whether prophylaxis should be given universally or to targeted 'high risk' sub-groups. We, therefore, analysed the cost-effectiveness of both prophylactic strategies. METHODS We performed a retrospective cross-sectional study of adult liver transplant (LT) recipients who developed CMV disease in 1997 and estimated the morbidity and costs associated with disease in these patients. These costs were compared with the estimated cost (based on a previous multi-centre study) of using oral ganciclovir prophylaxis in order to assess the potential cost-effectiveness of introducing different prophylactic regimes. RESULTS Universal and targeted prophylaxis would both have prevented all the likely mortality (2 deaths) from CMV disease in that year. The net cost of applying a targeted prophylaxis strategy would have been 206,275 pounds, (i.e. 103,137 pounds per death avoided). The cost per life year saved would have been 15,674 pounds. CONCLUSION We suggest that LT units should identify patients at high risk for the development of CMV disease and adopt a targeted prophylactic strategy.
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Affiliation(s)
- S Singhal
- Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
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Shi LW, Stewart GJ, Verran D, Maley M, McCaughan G. Cytomegalovirus serology status and early hepatic artery thrombosis following adult liver transplantation. Transplant Proc 2003; 35:421-2. [PMID: 12591469 DOI: 10.1016/s0041-1345(02)03929-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- L W Shi
- Australian National Liver Transplant Unit, Department of Microbiology, Royal Prince Alfred Hospital, Camperdown, Australia
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