Bacteria are the leading cause of infections after solid organ transplantation. In recent years, a progressive growth in the incidence of multidrug-resistant (MDR) and extensively-drug-reistant (XDR) ...strains has been observed. While methicillin-resistant Staphylococcus aureus (MRSA) infection is declining in non-transplant and SOT patients worldwide, vancomycin-resistant enterococci, MDR/XDR Enterobacteriaceae and MDR/XDR non-fermenters are progressively growing as a cause of infection in solid organ transplant (SOT) patients and represent a global threat. Some SOT patients develop recurrent infections, related to anatomical defects in many cases, which are difficult to treat and predispose patients to the acquisition of MDR pathogens. As the antibiotics active against MDR bacteria have several limitations for their use, which include less clinical experience, higher incidence of adverse effects and less knowledge of the pharmacokinetics of the drug, and, in most cases, are only available for parenteral administration, it is mandatory to know the main characteristics of these drugs to safely treat SOT patients with MDR bacterial infections. Nonetheless, preventive measures are the cornerstone of controlling the spread of these pathogens. Thus, applying the Center for Disease Control and Prevention’s and the European Society of Clinical Microbiology and Infectious Diseases’s recommended antibiotic policies and strategies to control the transmission of MDR strains in the hospital setting is essential for the management of SOT patients.
Solid organ transplantation (SOT) candidates and recipients are highly vulnerable to invasive pneumococcal diseases (IPD). Data on which to base optimal immunization recommendations for this ...population is scant. The national distribution of IPD serotypes led the Swiss Health Authorities to recommend in 2014 one dose of pneumococcal-13-valent-conjugate-vaccine (PCV13), without any subsequent dose of the 23-valent-polysaccharide-pneumococcal-vaccine (PPV23).
This is a retrospective analysis of pneumococcal immunity using a multiplex binding assay, to assess seroprotection rates against a selection of seven PCV13- and seven PPV23-serotypes in SOT-candidates and recipients evaluated and/or transplanted in 2014/2015 in the University Hospitals of Geneva. Seroprotection was defined as serotype-specific antibody concentration greater than 0.5 mg/l and overall seroprotection when this was achieved for ≥ 6/7 serotypes.
Pre-vaccination and at time of transplant sera were available for 35/43 (81%), and 43/43 (100%) SOT-candidates respectively. At listing, 17/35 (49%) SOT-candidates were seroprotected against PCV13 and 21/35 (60%) against PPV23 serotypes. Following one systematic dose of PCV13 at listing, 35/43 (81%) SOT-recipients were seroprotected at day of transplant against PCV13-serotypes and 34/43 (79%) against PPV23 serotypes, compared to 21/41 (51%) and 28/41 (68%) respectively in the controls transplanted in 2013, before the systematic PCV13-vaccination.
The systematic vaccination with PCV13 of all SOT candidates without additional PPV23 is a good strategy as it confers seroprotection against a wide range of pneumococcal serotypes. Indeed, one of five PCV13-vaccinated SOT-candidates was nevertheless not seroprotected at time of transplant, reflecting their partial immune competence, and indicating the need for additional dose of pneumococcal vaccines before transplant.
Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease ...(GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses.
Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; Anelloviridae (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1).
Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection. Video abstract.
In solid organ transplanted patients, annual influenza immunization is strongly recommended because of morbidity and mortality of influenza infections. In 2009, the rapid spread of a novel H1N1 ...influenza A virus led to the accelerated development of novel pandemic influenza vaccines. In Switzerland, the recipients received one dose of seasonal influenza and two doses of AS03‐adjuvanted H1N1 vaccines. This situation provided a unique opportunity to analyze the influence of novel adjuvanted influenza vaccines on the production of de novo anti‐HLA antibodies. We prospectively followed two independent cohorts including 92 and 59 kidney‐transplanted patients, assessing their anti‐HLA antibodies before, 6 weeks and 6 months after vaccination. Sixteen of 92 (17.3%) and 7 of 59 (11.9%) patients developed anti‐HLA antibodies. These antibodies, detected using the single antigen beads technology, were mostly at low levels and included both donor‐specific and non‐donor‐specific antibodies. In 2 of the 20 patients who were followed at 6 months, clinical events possibly related to de novo anti‐HLA antibodies were observed. In conclusion, multiple doses of influenza vaccine may lead to the production of anti‐HLA antibodies in a significant proportion of kidney transplant recipients. The long‐term clinical significance of these results remains to be addressed.
This study demonstrates an unexpectedly high rate of transient de novo anti‐HLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. See editorial by Kumar and Danziger‐Izakov on page 1561.
Because commensal viruses are defined by the immunologic tolerance afforded to them, any immunomodulation, such as is received during haematopoietic stem-cell transplantation, may shift the ...demarcation between innocuous viral resident and disease-causing pathogen.
We analysed by deep-sequencing the plasma virome of 40 allogeneic haematopoietic stem-cell transplantation patients 1 month after transplantation. Because human pegivirus (HPgV) was highly prevalent, we performed a 1-year screening of 122 plasma samples by specific real-time reverse transcription PCR assay. We used the log-rank test and the Gray test to assess association with outcomes, and the Mann-Whitney test and multivariable linear regression model to assess association with T-cell reconstitution.
Polyomaviruses (PyV) (20/40 patients), anelloviruses (16/40), pegiviruses (14/40) and herpesviruses (14/40) were most frequently identified, including ten cytomegalovirus; three Epstein-Barr virus; two herpes simplex virus type 1; one human herpesvirus 6b and one human herpesvirus 7; 18 Merkel cell–PyV; two BK-PyV; three PyV-6; and one JC-PyV. Papillomavirus and adenovirus were identified in 11 and two patients, respectively. The HPgV specific real-time reverse transcription PCR screening identified 51 of 122 positive samples, high virus loads and persistent infections up to 1 year after transplantation. Comparison between patients with or without HPgV infection at time of transplantation did not reveal a significant difference in infections, engraftment, survival, graft vs. host disease, relapse or immune reconstitution.
The blood virome after allogeneic haematopoietic stem-cell transplantation includes several DNA viruses, notably herpesviruses and PyV. Among RNA viruses, HPgV is highly prevalent and persists for several months, and it thus may deserve special attention in further research on immune reconstitution.
Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether ...KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n=57), kidney (n=223), liver (n=165) or lung (n=72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes-which in contrast to A haplotypes may contain multiple activating KIR genes-to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression) (hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29-0.75, P=0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26-0.77, P=0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22-1.53, P=0.28). These data indicate a prominent role for KIR-and presumably natural killer (NK) cells-in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression.
We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant ...recipients. Risk factors associated with CMV disease and graft failure‐free survival were analyzed using Cox regression models. One thousand two hundred thirty‐nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R− vs. R+, hazard ratio HR 5.36 95% CI 3.14–9.14, p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 95% CI 0.63–2.17, p = 0.63). CMV disease was not associated with a lower graft failure‐free survival (HR 1.27 95% CI 0.64–2.53, p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure‐free survival after a median of 1.05 years of follow‐up (HR 1.63 95% CI 1.01–2.64, p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.
In this nationwide cohort of solid organ transplant recipients, the authors find that the incidence of cytomegalovirus disease is similar irrespective of the antiviral preventive strategy used (preemptive vs. prophylaxis), although patients who received antiviral prophylaxis have better graft failure‐free survival.
Background
The burden of enterococcal infections has increased over the last decades with vancomycin‐resistant enterococci (VRE) being a major health problem. Solid organ transplantation is ...considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence.
Methods
We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome.
Results
Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 47.2% infections, 205 52.3% colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person‐year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person‐year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events.
Conclusions
Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.
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