Antimicrobial stewardship programs in solid-organ transplant recipients in Switzerland.

INTRODUCTION: Antimicrobial stewardship programs (ASPs) are essential for minimizing the emergence of antimicrobial resistance, while improving patient outcomes. The current status of ASP in the field of organ transplantation in Switzerland has not been well characterized. METHODS: We describe in this article the current status of ASP and discuss challenges and opportunities of implementing ASP dedicated to solid-organ transplant (SOT) recipients in Switzerland. RESULTS: ASP have been implemented in the Swiss healthcare system over the last years, although specific strategies for SOT recipients are mostly based on transplant infectious diseases (TID) consultations rather than structured institutional interventions. Even so, there is a unique opportunity for developing a successful ASP in Switzerland that also specifically addresses areas of practice relevant to SOT recipients. This is due to the existent network of TID specialists in close collaboration with transplant physicians, the small number of centers involved in the care of transplant recipients, and the development of the Swiss Transplant Cohort Study (STCS), a prospective nationwide cohort of SOT recipients in Switzerland. The STCS can identify actual challenges through the updated reports on the epidemiology on transplant infections, accurately monitor the impact of potential antimicrobial stewardship interventions, and represent an opportunity for nesting of pragmatic randomized controlled trials to address key questions about optimized antibiotic use for SOT recipients. CONCLUSIONS: Although ASP in SOT recipients rely more on specific TID consultations than in general antimicrobial stewardship teams, we identified several opportunities for the implementation of a successful ASP in Switzerland

Employment 12 months after kidney transplantation: an in-depth bio-psycho-social analysis of the Swiss Transplant Cohort

Return to work with or after a chronic disease is a dynamic process influenced by a variety of interactions between personal, work, societal and medical resources or constraints. The aim of this study was to identify predictors for employment 12 months after transplantation in kidney patients, applying a bio-psycho-social model. All kidney patients followed in the Swiss Transplant Cohort between May 2008 and December 2012, aged 18 to 65 were assessed before, 6 and 12 months after transplantation. Of the 689 included patients, 56.2% worked 12 months post- transplantation compared to 58.9% pre-transplantation. Age, education, self-perceived health (6 months post- transplantation), pre- transplantation employment and receiving an organ from a living donor are significant predictors of employment post- transplantation. Moreover, while self-perceived health increased post- transplantation, depression score decreased only among those employed 12 months post- transplantation. Pre- transplantation employment status was the main predictor for post- transplantation employment (OR = 18.6) and was associated with sex, age, education, depression and duration of dialysis. An organ from a living donor (42.1%) was more frequent in younger patients, with higher education, no diabetes and shorter waiting time to surgery. Transplantation did not increase employment in end-stage kidney disease patients but helped maintaining employment. Pre-transplantation employment has been confirmed to be the most important predictor of post-transplantation employment. Furthermore, socio-demographic and individual factors predicted directly and indirectly the post-transplantation employment status. With living donor, an additional predictor linked to social factors and the medical procedure has been identified

Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.

In cystic fibrosis (CF) patients, chronic airway infection by Pseudomonas leads to progressive lung destruction ultimately requiring lung transplantation (LT). Following LT, CF-adapted Pseudomonas strains, potentially originating from the sinuses, may seed the allograft leading to infections and reduced allograft survival. We investigated whether CF-adapted Pseudomonas populations invade the donor microbiota and adapt to the non-CF allograft. We collected sequential Pseudomonas isolates and airway samples from a CF-lung transplant recipient during two years, and followed the dynamics of the microbiota and Pseudomonas populations. We show that Pseudomonas invaded the host microbiota within three days post-LT, in association with a reduction in richness and diversity. A dominant mucoid and hypermutator mutL lineage was replaced after 11 days by non-mucoid strains. Despite antibiotic therapy, Pseudomonas dominated the allograft microbiota until day 95. We observed positive selection of pre-LT variants and the appearance of novel mutations. Phenotypic adaptation resulted in increased biofilm formation and swimming motility capacities. Pseudomonas was replaced after 95 days by a microbiota dominated by Actinobacillus. In conclusion, mucoid Pseudomonas adapted to the CF-lung remained able to invade the allograft. Selection of both pre-existing non-mucoid subpopulations and of novel phenotypic traits suggests rapid adaptation of Pseudomonas to the non-CF allograft

Use of statins after liver transplantation is associated with improved survival: results of a nationwide study.

BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated

The impact of perceived donor liver quality on post-transplant outcome.

BACKGROUND We analysed the impact of perceived liver donor quality on transplant recipient outcomes. METHODS this prospective cohort study included all deceased liver donors during 2008-2018 in the Swiss Transplant Cohort Study. Perceived low-quality liver donors were defined when refused for ≥5 top listed recipients or for all recipients in at least one centre before being transplanted. The effect of liver donor quality on relisting or recipient death at 1 week and 1 year after transplantation was analysed using Kaplan-Meier and Cox proportional hazard models. A 1:3 matching was also performed using a recipient score. RESULTS Of 973 liver donors, 187 (19.2%) had perceived poor-quality. Males, obesity, donation after circulatory death and alanine aminotransferase values were significantly associated with perceived poor-quality, with no significant effect of the perceived quality on re-listing or death within the first week and first year post-transplant [(aHR) = 1.45, 95% CI: (0.6, 3.5), P = 0.41 and aHR = 1.52 (95% CI 0.98-2.35), P = 0.06], adjusting by recipient age and gender, obesity, diabetes, prior liver transplantation and model for end-stage liver disease (MELD) score. At 1 year, prior liver transplantation and higher MELD score associated with higher risk of re-listing or death. CONCLUSION Comparable post-transplant outcomes with different perceived quality liver donors stresses the need to improve donor selection in liver transplantation

A National Survey Comparing Patients' and Transplant Professionals' Research Priorities in the Swiss Transplant Cohort Study.

We aimed to identify, assess, compare and map research priorities of patients and professionals in the Swiss Transplant Cohort Study. The project followed 3 steps. 1) Focus group interviews identified patients' (n = 22) research priorities. 2) A nationwide survey assessed and compared the priorities in 292 patients and 175 professionals. 3) Priorities were mapped to the 4 levels of Bronfenbrenner's ecological framework. The 13 research priorities (financial pressure, medication taking, continuity of care, emotional well-being, return to work, trustful relationships, person-centredness, organization of care, exercise and physical fitness, graft functioning, pregnancy, peer contact and public knowledge of transplantation), addressed all framework levels: patient (n = 7), micro (n = 3), meso (n = 2), and macro (n = 1). Comparing each group's top 10 priorities revealed that continuity of care received highest importance rating from both (92.2% patients, 92.5% professionals), with 3 more agreements between the groups. Otherwise, perspectives were more diverse than congruent: Patients emphasized patient level priorities (emotional well-being, graft functioning, return to work), professionals those on the meso level (continuity of care, organization of care). Patients' research priorities highlighted a need to expand research to the micro, meso and macro level. Discrepancies should be recognized to avoid understudying topics that are more important to professionals than to patients

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification

Bacteremia During the First Year After Solid Organ Transplantation: An Epidemiological Update.

BACKGROUND There are limited contemporary data on the epidemiology and outcomes of bacteremia in solid organ transplant recipients (SOTr). METHODS Using the Swiss Transplant Cohort Study registry from 2008 to 2019, we performed a retrospective nested multicenter cohort study to describe the epidemiology of bacteremia in SOTr during the first year post-transplant. RESULTS Of 4383 patients, 415 (9.5%) with 557 cases of bacteremia due to 627 pathogens were identified. One-year incidence was 9.5%, 12.8%, 11.4%, 9.8%, 8.3%, and 5.9% for all, heart, liver, lung, kidney, and kidney-pancreas SOTr, respectively (P = .003). Incidence decreased during the study period (hazard ratio, 0.66; P < .001). One-year incidence due to gram-negative bacilli (GNB), gram-positive cocci (GPC), and gram-positive bacilli (GPB) was 5.62%, 2.81%, and 0.23%, respectively. Seven (of 28, 25%) Staphylococcus aureus isolates were methicillin-resistant, 2/67 (3%) enterococci were vancomycin-resistant, and 32/250 (12.8%) GNB produced extended-spectrum beta-lactamases. Risk factors for bacteremia within 1 year post-transplant included age, diabetes, cardiopulmonary diseases, surgical/medical post-transplant complications, rejection, and fungal infections. Predictors for bacteremia during the first 30 days post-transplant included surgical post-transplant complications, rejection, deceased donor, and liver and lung transplantation. Transplantation in 2014-2019, CMV donor-negative/recipient-negative serology, and cotrimoxazole Pneumocystis prophylaxis were protective against bacteremia. Thirty-day mortality in SOTr with bacteremia was 3% and did not differ by SOT type. CONCLUSIONS Almost 1/10 SOTr may develop bacteremia during the first year post-transplant associated with low mortality. Lower bacteremia rates have been observed since 2014 and in patients receiving cotrimoxazole prophylaxis. Variabilities in incidence, timing, and pathogen of bacteremia across different SOT types may be used to tailor prophylactic and clinical approaches

Donor-derived fulminant herpes simplex virus hepatitis after liver transplantation: Two cases and review of literature

BACKGROUND Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor-derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients. The fatal outcome is mostly due to delayed diagnosis and treatment, which is explained by the lack of clinical specificity of HSV hepatitis. METHODS We report two cases of fatal donor-derived HSV hepatitis in liver-transplanted recipients. We reviewed all published cases of donor-derived HSV infections after SOT with an evaluation of the presence of prophylaxis and outcome. RESULTS In both liver recipients, the retrospective determination of HSV serostatus was negative, and both cases occurred in the absence of cytomegalovirus or HSV prophylaxis. A review of the literature showed a significant series of cases of severe hepatitis, mostly fatal, as well as the absence of specific preventive therapy guidelines in cases of HSV serology mismatch. CONCLUSIONS The occurrence of two fatal donor-derived hepatitis made the Swiss Transplant Infectious Diseases working group modify its national recommendations regarding pretransplant serostatus determination and HSV prophylaxis after liver transplantation. Further studies are needed to assess this approach