Infections In Solid Organ Transplantation Research Articles

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants.

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV-specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2(neg) γδ T cells in controlling CMV infection. Here, we assessed if Vδ2(neg) γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high-risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R-) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2(neg) γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2(neg) γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2(neg) γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2(neg) γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral-resistant mutant CMV strains was associated with delayed Vδ2(neg) γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2(neg) γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

BackgroundBacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Methods and FindingsBetween 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients’ mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.ConclusionThe isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

Solid organ transplantation: hypogammaglobulinaemia and infectious complications after solid organ transplantation.

Solid organ transplantation: hypogammaglobulinaemia and infectious complications after solid organ transplantation.

A patient self-collection method for longitudinal monitoring of respiratory virus infection in solid organ transplant recipients

BackgroundMethods for the longitudinal study of respiratory virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (SOT) recipients. ObjectivesTo assess the feasibility and patient acceptability of self-collected foam nasal swabs for detection of respiratory viruses in SOT recipients and to define the virologic and clinical course. Study designWe prospectively monitored the course of symptomatic respiratory virus infection in 18 SOT patients (14 lung, 3 liver, and 1 kidney) using patient self-collected swabs. ResultsThe initial study sample was positive in 15 patients with the following respiratory viruses: rhinovirus (6), metapneumovirus (1), coronavirus (2), respiratory syncytial virus (2), parainfluenza virus (2), and influenza A virus (2). One hundred four weekly self-collected nasal swabs were obtained, with a median of 4 samples per patient (range 1–17). Median duration of viral detection was 21 days (range 4–77 days). Additional new respiratory viruses detected during follow-up of these 15 patients included rhinovirus (3), metapneumovirus (2), coronavirus (1), respiratory syncytial virus (1), parainfluenza virus (1), and adenovirus (1). Specimen collection compliance was good; 16/18 (89%) patients collected all required specimens and 79/86 (92%) follow-up specimens were obtained within the 7±3 day protocol-defined window. All participants agreed or strongly agreed that the procedure was comfortable, simple, and 13/14 (93%) were willing to participate in future studies using this procedure. ConclusionSelf-collected nasal swabs provide a convenient, feasible, and patient-acceptable methodology for longitudinal monitoring of upper respiratory virus infection in SOT recipients.

Dynamics of gd T Cell Expansion Can Predict the Resolution of CMV Infection and the Emergence of a Mutant Viral Strain in Kidney Transplant Recipients.

Cytomegalovirus (CMV) infection in solid organ transplantation is associated with increased morbidity and mortality, particularly in the case of the emergence of a CMV mutant strain with anti-viral drug resistance. In this situation, immune monitoring assays should provide relevant clinical information on efficient CMV-specific T cells response. For many years, we have shown that gd T lymphocytes (gd-TL) are involved in the control of CMV infection. The purpose of this study was to assess if gd-TL kinetics can predict the resolution of CMV infection in high risk patients: D+ R- and R+ with anti-thymocyte globulin - ATG, or the emergence of a mutant strain. Methods gd-TL kinetics has been described in D+ R- or R+/ATG kidney transplant recipients between 2003 and 2011. This kinetics was compared between infected and non infected patients and between patients with and without mutation. gd-TL expansion was estimated by a linear mixed model, the time of expansion was defined as the date of occurrence of this expansion from the beginning of infection. Results 167 patients D+ R- (93 infected and 74 non-infected) and 104 R+/ATG (74 infected and 30 non-infected) patients were included. The gd-TL expansion following CMV infection was comparable in D+R- and R+/ATG patients. Time of gd-TL expansion was highly correlated with the duration of DNAemia (r=0.91, p < 0.0001). The delay of gd-TL expansion was closely associated with the presence of a mutant strain (p < 0.0007). This mutation was predicted by persistent DNAemia after 39 days of gd-TL expansion (AUC= 0.76). Conclusion In high risk patients, gd-TL expansion is related to the resolution of CMV infection. Conversely, the delay of expansion and the persistence of DNAemia after expansion are predictive of the occurrence of a mutant strain. Monitoring gd-TL could be useful during CMV infection in order to predict the resolution of the infection and the emergence of a mutant viral strain.

Diarrhea caused by viruses in transplant recipients.

Diarrhea is a common complication after solid organ transplantation, and viruses are emerging as important but underestimated causative agents. Viral infections in solid organ transplant (SOT) recipients can result in severe and prolonged diarrhea with significant patient morbidity and graft complications. Cytomegalovirus remains the most common of the viruses to cause diarrhea, but other viruses are being increasingly recognized, including norovirus, rotavirus, and adenovirus. This article reviews the epidemiology, clinical presentation, diagnosis, management, and outcomes of these viral causes of diarrhea in SOT patients.

Decreased immunoglobulin G levels after living‐donor liver transplantation is a risk factor for bacterial infection and sepsis

Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

Multidrug-Resistant Bacteria in Organ Transplantation: An Emerging Threat with Limited Therapeutic Options

Multidrug-resistant organisms (MDROs) are an emerging threat in solid organ transplantation (SOT). The changing epidemiology of these MDROs is reviewed along with the growing evidence regarding risk factors and outcomes associated with both colonization and infection in SOT. The management of these infections is complicated by the lack of antimicrobial agents available to treat these infections, and only a handful of new agents, especially for the treatment of MDR GNR infections, are being evaluated in clinical trials. Due to the increased prevalence of MDROs and limited treatment options, as well as organ shortages, transplant candidacy and use of organs from donors with evidence of MDRO colonization and/or infection remain controversial. Increasing collaboration between transplant programs, individual practitioners, infection control programs, and researchers in antimicrobial development will be needed to face this challenge.

Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented.

Role of Primary Structure Variation in Structure and Function of Calcineurin

A. fumigatus is one of the leading causes of invasive fungal infections in solid organ transplant and adult stem cell transplant recipients. It is estimated that over 20% of Americans are infected with T. gondii. T. gondii is life threatening in immunocompromised patients. Here, we study the enzyme calcineurin that is critical for the virulence and pathogenicity of these organisms. CaN is activated when calcium‐loaded calmodulin (CaM) binds the regulatory domain (RD) of the A subunit. Upon binding to CaM, the RD of human calcineurin transitions from a disordered state to an ordered state, gaining alpha helical structure. Research done in our lab has determined that the C‐terminus of the RD forms a helix (distal helix) that is necessary for the normal function of human CaN. In A. fumigatus and T. gondii, the sequence for this helix is deleted. A. fumigatus and T. gondii CaN contain modular insertions and deletions in the RD. A Ser/Pro rich region (SPRR) found in the RD that is unique to A. fumigatus is critical for the function of CaN and survival. The phosphorylation of this SPRR has also been shown to be critical in the pathogenicity of the organism. Investigations into the protein sequence of CaN of T. gondii show a unique insertion in the same area as the SPRR in A. fumigatus, but the function of this insertion is unknown. Thus, we are probing into how structure affects function through evolutionary variations.

Aspergillosis in Solid Organ Transplantation

Invasive aspergillosis (IA) occurs in 1–15% of the solid organ transplant (SOT) recipients. Mortality rate in transplant recipients with IA historically has ranged from 65% to 92% (1–4). However, currently reported mortality rate in IA among SOT recipients is 22% (5). An estimated 9.3– 16.9% of all deaths in transplant recipients in the first year have been considered attributable to IA (6). Although the outcomes have improved in the current era, IA remains a significant posttransplant complication in SOT recipients. The review herein discusses the epidemiologic characteristics, risk factors, diagnostic laboratory assays and the approach to antifungal prophylaxis and treatment of IA in SOT recipients.

Emerging Fungal Infections in Solid Organ Transplantation

Emerging Fungal Infections in Solid Organ Transplantation

Multidrug-Resistant Gram-Negative Bacteria Infections in Solid Organ Transplantation

Multidrug-Resistant Gram-Negative Bacteria Infections in Solid Organ Transplantation

Introduction: Infections in Solid Organ Transplantation

Introduction: Infections in Solid Organ Transplantation

Candida Infections in Solid Organ Transplantation

Abbreviations: ABCD, amphotericin B colloidal dispersion; ABLC, amphotericin B lipid complex; AmB, amphotericin B; AmB-d, deoxycholate amphotericin; BDG, 1–3 b glucan; CNI, calcineurin inhibitor; CSF, cerebrospinal fluid; 5-FC, flucytosine; GI, gastrointestinal; IFI, invasive fungal infection; LAmB, liposomal amphotericin B; LFAmB, lipid formulation of amphotericin B; PCR, polymerase chain reaction; PNA-FISH, peptide nucleic acid fluorescent in situ hybridization assay; TDM, therapeutic drug monitoring.

Nontuberculous Mycobacterial Infections in Solid Organ Transplantation

Nontuberculous Mycobacterial Infections in Solid Organ Transplantation

Vancomycin-Resistant Enterococcus Infections in Solid Organ Transplantation

Vancomycin-Resistant Enterococcus Infections in Solid Organ Transplantation

Urinary Tract Infections in Solid Organ Transplantation

Urinary Tract Infections in Solid Organ Transplantation

Nocardia Infections in Solid Organ Transplantation

Nocardia Infections in Solid Organ Transplantation

Donor-Derived Infections in Solid Organ Transplantation

Summary of potential donor-derived infectious diseasetransmissions reported to the United States organ procurementand transplantation network 2005–2011 (2)Number of Number ofNumber recipients with DDI-attributableInfection of donor confirmed recipienttype reports transmission deathsViruses 1 166 48 16Bacteria 2 118 34 9Fungi 3 75 31 10Mycobacteria 4 53 10 3Parasites 5 35 22 7 1 Viruses: adenovirus, HBV, HCV, HEV, HIV, HTLV, herpes simplex,influenza, LCMV, parainfluenza (PIV)-3, parvovirus B19, rabies,West Nile virus. 2 Bacteria: Acinetobacter, Brucella, Enterococcus (including VRE),Ehrlichiaspp,E.coli,Gram-positivebacteria,Klebsiella,Legionella,Listeria, Borrelia burgdorferi, Nocardia, Pseudomonas, RockyMountain Spotted Fever, Serratia, S. aureus (MRSA), Streptococ-cus spp, Treponema pallidum, Veillonella;bacterialmeningitis&bacterial emboli. 3 Fungi: Aspergillus spp, Candida spp, Coccidioides imitis, Cryp-tococcus neoformans, Histoplasma capsulatum, Scopulariopsis,zygomyces. 4 Mycobacteria: tuberculosis, non-TB mycobacteria.