The Impact ofClostridium difficileInfection on Future Outcomes of Solid Organ Transplant Recipients

2018 ◽  
Vol 39 (5) ◽  
pp. 563-570 ◽  
Author(s):  
Ruihong Luo ◽  
Janice M. Weinberg ◽  
Tamar F. Barlam

OBJECTIVEClostridium difficileinfection (CDI) is common in solid organ transplant (SOT) recipients, but few studies have examined long-term outcomes. We studied the impact of CDI after SOT on mortality and transplant organ complication-related hospitalizations (TOH).METHODSSOT recipients ≥18 years of age with at least 1 year of posttransplant data were analyzed using the MarketScan database for 2007–2014. Patients who died within one year of transplant were followed until death. Patients were grouped as early CDI (ie, first occurrence ≤90 days posttransplant), late CDI (ie, first occurrence >90 days posttransplant) and controls (ie, no CDI occurrence during follow-up). The risk of mortality or TOH after CDI was evaluated using Cox and logistic regressions, respectively.RESULTSOverall, 96 patients had early CDI, 97 patients had late CDI, and 5,913 patients were used as controls. The risk for death was significantly higher in the early CDI group than the control group (hazard ratio [HR],1.92; 95% confidence interval [CI], 1.12–3.29;P=.018); there was no significant difference between the late CDI group and the control group (HR, 0.86; 95% CI, 0.38–1.94;P=.717). Both the early CDI group (odds ratio [OR], 2.19; 95% CI, 1.45–3.31;P<.001) and the late CDI group (OR, 4.36; 95% CI, 2.84–6.71;P<.001) had higher risk for TOH than the control group. For those patients who survived >90 days posttransplant, both the early CDI group (n=89) and the late CDI group (n=97) had increased risk for death or TOH during follow-up than the control group (n=5,734).CONCLUSIONThough our study could not prove causality, both early and late CDI occurrence in SOT recipients were associated with worse future outcomes than for SOT recipients without CDI.Infect Control Hosp Epidemiol2018;39:563–570

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S834-S835
Author(s):  
Toni A Campanella ◽  
Amanda Roy ◽  
Thomas J Gintjee ◽  
Monica Donnelley ◽  
Conan MacDougall ◽  
...  

Abstract Background Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), is 60% bioavailable. Manufacturer-recommended doses are adjusted for creatinine clearance (CrCl), but not weight (wt), while GCV doses are adjusted for CrCl and wt. Patients exposed to excess GCV by not wt-adjusting VGC doses may be at risk of hematologic toxicity. The purpose of this study was to investigate the impact of body weight on VGC toxicity in solid organ transplant (SOT) recipients. Methods This was a multicenter retrospective study at three academic medical centers of adult SOT recipients who received VGC for CMV prophylaxis between January 2016 and August 2019. The primary outcome was first occurrence of leukopenia within six months post-transplant. The primary predictor was the ratio between the patient’s estimated GCV exposure based on the initial VGC dose prescribed and the equivalent prophylactic GCV dose accounting for the patient’s CrCl and wt (rVGC:GCV). Results The study included 231 patients, mostly lung (59%) and kidney (KT, 28%) transplants (Table 1). The rVGCV:GCV was 4.4 (range, 0.6-25.1, SD 4.5), and was significantly higher in KT (7.7 vs 3.0, p &lt; 0.001). Leukopenia occurred in 133 patients (57.5%). After adjustment for type of transplant, rVGC:GCV ratio was not associated with increased odds (OR 0.97, 95% CI 0.91-1.04) or hazard of (HR 0.99, 95% CI 0.95-1.04) leukopenia. Exploratory analysis suggested threshold effects and interaction with transplant type: a rVGCV:VGC of &gt; 3 was associated with time to leukopenia (HR 2.02, 95% CI 1.09-3.74) among non-KT patients but not KT patients (HR 0.99, 95% CI 0.56-1.76) (Figure 1). Table 1 Figure 1 Conclusion Initial doses of VGC used for SOT CMV prophylaxis are estimated to result in significantly higher GCV exposures than IV GCV doses. A relationship with risk of leukopenia was only seen in non-KT patients, possibly because of rapid recovery of renal function and dose adjustment in KT patients. Disclosures Jason C. Gallagher, PharmD, FIDP, FCCP, FIDSA, BCPS, Allergan (Consultant)Astellas (Consultant)Merck (Consultant, Grant/Research Support)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant)


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S925-S926
Author(s):  
Sara Belga ◽  
Cristina Hernandez ◽  
Dima Kabbani ◽  
Carlos Cervera

Abstract Background Valganciclovir (VGCV) prophylaxis in solid-organ transplant patients (SOT) is limited by myelotoxicity. We aimed to analyze the impact of VGCV prophylaxis on myelotoxicity and risk factors for its occurrence. Methods Retrospective single-center cohort study of adult CMV-seronegative recipients transplanted between July 2005 and November 2017. CMV D+/R− recipients received 3 to 6 months of VGCV prophylaxis whereas CMV D-/R- received no VGCV. Definitions: leukopenia < 3.5 × 109/L, significant neutropenia < 1.0 × 109/L and significant thrombocytopenia < 50 × 109/L. Results A total of 363 SOT recipients were included, 169 (47%) CMV D+/R− and 194 (53%) CMV D−/R−, with a mean age of 49.5 years and 275 (76%) males; types of organ transplant: 133 (37%) liver, 181 (50%) kidney, 37 (10%) simultaneous kidney-pancreas and 12 (3%) other. Although there was no difference in the incidence of significant neutropenia or thrombocytopenia per transplant type, leukopenia in the first year was more common in liver transplant patients (P < 0.001). New onset leukopenia post-SOT, significant neutropenia (Figure 1) and significant thrombocytopenia in the first year were more common in patients receiving VGCV: 116 D+/R− (69%) vs. 52 D−/R− (31%), P < 0.001; 86 (91%) vs. 9 (9%), P < 0.001; 8 (80%) vs. 2 (20%), P = 0.050; respectively. G-CSF was used more frequently in patients receiving prophylaxis (60% CMV D+/R− vs. 10% CMV D−/R−, P < 0.001). Significant neutropenia had no impact on long-term mortality adjusted by age and transplant type (HR 1.1, 95% CI 0.6–2.1, P = 0.709). Significant neutropenia led to decrease immunosuppression in 90% of patients (vs. 46%, P < 0.001) and was associated with increased risk of rejection (HR 8.5, P < 0.001). In multivariate analysis for significant neutropenia in the first year, VGCV prophylaxis was the only predictor of this outcome after adjusting for confounders (HR 15.1, 95% CI 7.5–30.1, P < 0.001). Conclusion VGCV prophylaxis increased the risk of significant neutropenia by 15-fold post-SOT. No other clinical variables were useful to predict this complication. Therefore, complete blood count monitoring is still needed for all SOT recipients receiving VGCV prophylaxis. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S558-S558
Author(s):  
Jesus Sotelo ◽  
Esra Akkoyun ◽  
Giselle S Chery ◽  
Amal Aqul ◽  
Dev M Desai ◽  
...  

Abstract Background The impact of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection among pediatric solid organ transplant (SOT) recipients remains unclear. We sought to characterize the clinical epidemiology and outcomes following SARS-CoV-2 infection among pediatric SOT recipients in Dallas, TX. Methods Retrospective review of all SOT recipients with laboratory confirmed COVID-19 infection from March 1, 2020 –March 31, 2021. Demographic, clinical, and outcome data were stratified by transplant type and disease severity. Fischer’s exact test and Kruskall-Wallis test were used to evaluate risk factors for more severe disease among hospitalized children. Results Twenty-six SOT recipients with a median age of 14 years were included in the study. Fifteen (58%) were female, eighteen (69%) were Hispanic and thirteen (50%) were overweight/obese. Median time post-transplant was 3.6 years (1311 days, interquartile range (IQR) 394-2881). Fourteen patients were liver recipients, seven kidney, three heart, and two multiorgan. The majority of patients (65%) had a known community exposure and presented with fever (50%), cough (38%) and GI symptoms (19%). Half of all cases were hospitalized (n=13), with 2 requiring intensive care unit (ICU) admission, but no patients required positive pressure ventilation. Median hospital stay was 3 days. Five of the thirteen hospitalized patients were categorized as having moderate disease. No patients developed severe disease and there were no deaths. Older children, as well as children with multiple co-morbidities were noted on univariate analysis to be at higher risk for moderate, as compared to mild, disease. Conclusion SARS-CoV-2 infection among pediatric SOT recipients are at increased risk for hospital admission but demonstrate an overall mild /moderate disease course. Larger studies are required to elucidate the risk of morbidity between pediatric SOT recipients and immunocompetent children with SARS-CoV-2. Disclosures Amal Aqul, MD, Albireo pharma Inc. (Consultant)


2021 ◽  
pp. 152692482110246
Author(s):  
Aileen C. Scheibner ◽  
Crystal Franco-Martinez ◽  
Elisabeth Kincaide ◽  
Reed Hall ◽  
Christina Long

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. Transplanted organs included kidney (n = 22), lung (n = 18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.


2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
T Kitano ◽  
M Science ◽  
N Nalli ◽  
K Timberlake ◽  
U Allen ◽  
...  

Abstract Background Solid-organ transplant (SOT) patients are more vulnerable to infections by antimicrobial-resistant organisms (AROs) because of their hospital exposure, compromised immune systems, and antimicrobial exposure. Therefore, it may be useful for transplant facilities to create transplant-specific antibiograms to direct empirical antimicrobial regimens and monitor trends in antimicrobial resistance. Methods SOT (i.e., lung, liver, renal, and heart) antibiograms were created using antimicrobial susceptibility data on isolates from 2012 to 2018 at The Hospital for Sick Children, a tertiary pediatric hospital and transplant center in Toronto, Ontario. The Clinical Laboratory Standards Institute (CLSI) guidelines were followed to generate the antibiograms. The first clinical isolate of a species from a patient in each year was included irrespective of body site; duplicates were eliminated and surveillance cultures were excluded. Results from 2 years of data were pooled on a rolling basis to achieve an adequate sample size in both SOT and hospital-wide antibiogram. The SOT antibiogram was then compared with the hospital-wide antibiogram of the compatible 2 pooled years from 2012 to 2018. For subgroup analyses in the SOT population, organ-specific antibiograms and transplant timing-specific antibiograms (pretransplant, post-transplant &lt;1 year, and post-transplant ≥1 year) between transplant and sample collection dates were analyzed. All proportions were compared using the χ 2 test. Results The top 5 organisms in one (2 year) analysis period of the SOT antibiogram were Escherichia coli (n = 29), Staphylococcus aureus (n = 28), Pseudomonas aeruginosa (n = 20), Enterobacter cloacae complex (n = 18), and Klebsiella pneumoniae (n = 17). For E.coli, susceptibility in the SOT antibiogram was significantly lower than those in the hospital-wide antibiogram in 2017/2018 for ampicillin (27% vs. 48%; P = 0.015), piperacillin/tazobactam (55% vs. 87%; P &lt; 0.001), cefotaxime (59% vs. 88%; P &lt; 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P &lt; 0.001), but not significantly different for gentamicin (94% vs. 91%; P = 0.490), tobramycin (88% vs. 90%; P = 0.701) and amikacin (100% vs. 99%; P = 0.558). These findings were consistent throughout the study period in E.coli. There was no statistically significant difference between the SOT and hospital-wide antibiograms for other organisms. There were no significant differences in susceptibility between organ-specific antibiograms or transplant timing-specific antibiograms in 2012–2018. Conclusions We found that E.coli from the SOT population had a significantly lower sensitivity to all antimicrobials, except aminoglycosides, compared with those from the hospital-wide population. Other organisms had similar susceptibility to the hospital-wide population. Developing a SOT antibiogram will assist in revising and improving empiric treatment guidelines for this population.


Author(s):  
D. Kiessling ◽  
C. Rennings ◽  
M. Hild ◽  
A. Lappas ◽  
T. S. Dietlein ◽  
...  

Abstract Purpose To determine the impact of failed ab-interno trabeculectomy on the postoperative outcome of subsequent XEN45 gel stent (Allergan, CA, USA) implantation in pseudophakic eyes. Methods In this retrospective single-center study, we included 60 pseudophakic eyes from 60 participants who underwent XEN45 gel stent implantation. Thirty eyes each underwent primary stent implantation (control group) or had previously undergone a failed ab-interno trabeculectomy (trabectome group). The groups were matched at a 1:1 ratio based on the following criteria: preoperative and maximum Intraocular pressure (IOP), preoperative medication score, cup/disk-ratio, follow-up time, best-corrected visual acuity at baseline, age, and the proportion of patients classified as primary open angle glaucoma or exfoliation glaucoma. We defined a successful surgery by the following three scores: an IOP reduction > 20% and IOP at the longest follow-up < 21 mmHg (Score A) or < 18 mmHg (Score B) or IOP ≤ 15 mmHg and an IOP reduction ≥ 40% (Score C). One open conjunctival revision was allowed in all scores, and a repeat surgery was considered a failure. Results Following an average follow-up period of 22 ± 12 months, we observed a mean IOP reduction of 38%, from 23.5 ± 5.2–14.5 ± 5.0 mmHg. Comparative analyses between the groups did not reveal a significant difference in the postoperative IOP, postoperative medication score, side effects, revision rate, repeat surgery rate, or success rate. Conclusions Trabectome is a viable first-line procedure for medically uncontrolled glaucoma before filtering ab-interno microstent surgery is considered.


BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043731
Author(s):  
Adnan Sharif ◽  
Javeria Peracha ◽  
David Winter ◽  
Raoul Reulen ◽  
Mike Hawkins

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.


2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  

Background: Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause high morbidity and mortality in solid organ transplant (SOT) recipients. There are conflicting data with respect to the impact of CMV on IA development in SOT recipients. Methods: A literature search was conducted from existence through to 2 April 2021 using MEDLINE, Embase, and ISI Web of Science databases. This review contained observational studies including cross-sectional, prospective cohort, retrospective cohort, and case-control studies that reported SOT recipients with post-transplant CMV (exposure) and without post-transplant CMV (non-exposure) who developed or did not develop subsequent IA. A random-effects model was used to calculate the pooled effect estimate. Results: A total of 16 studies were included for systematic review and meta-analysis. There were 5437 SOT patients included in the study, with 449 SOT recipients developing post-transplant IA. Post-transplant CMV significantly increased the risk of subsequent IA with pORs of 3.31 (2.34, 4.69), I2 = 30%. Subgroup analyses showed that CMV increased the risk of IA development regardless of the study period (before and after 2003), types of organ transplantation (intra-thoracic and intra-abdominal transplantation), and timing after transplant (early vs. late IA development). Further analyses by CMV definitions showed CMV disease/syndrome increased the risk of IA development, but asymptomatic CMV viremia/infection did not increase the risk of IA. Conclusions: Post-transplant CMV, particularly CMV disease/syndrome, significantly increased the risks of IA, which highlights the importance of CMV prevention strategies in SOT recipients. Further studies are needed to understand the impact of programmatic fungal surveillance or antifungal prophylaxis to prevent this fungal-after-viral phenomenon.


2018 ◽  
Vol 25 (5) ◽  
pp. 104-110
Author(s):  
V. S. Uchaeva ◽  
Yu. A. Vasiliev ◽  
A. S. Gracheva ◽  
O. V. Gulenko ◽  
I. G. Udina

Aim. This research was designed to conduct an associative population genetic study for the consideration of the impact of SNP C677T of the gene MTHFR in the congenital maxillofacial developmental anomalies (CMDA): congenital cleft lip (CCL), congenital cleft palate (CCP), congenital cleft lip and palate (CCLP) in the Krasnodar territory. The aim of the study is to establish the associations between SNP C677T of the gene MTHFR and the development of congenital cleft lip and/ or palate.Materials and methods. In this research, the peculiarities of distribution of SNP C667T of the gene MTHFR in children with congenital cleft lip and/or palate (n=223) and their mothers (n=78) in comparison with the control group (n=124) were studied in the Krasnodar territory. The genetic demographic questionnaires were gathered for children with CMDA, the information about diagnosis was obtained from the medical records. The biological samples, including blood or scrapings of oral mucosa, were collected from children with the pathology and their mothers. The DNA was extracted from the samples by the standard method. The study of the peculiarities of distribution of alleles of SNP C677T of the gene MTHFR was performed by PCR-PFLP with endonuclease Hinf I or by tetra-primer ARMS-PCR method in children with CCL, CCP, CCLP, their mothers and the control group. Statistical processing of the obtained data was performed by the algorithms of the “Statistica” program.Results. While comparing the profiles of frequencies of SNP C677T in children with CCL, CCP and CCLP with the control group, there were identified no significant differences in the frequency of this SNP and no peculiarities of genotypes distribution. There was identified a significant difference in the peculiarities of genotypes distribution with the control group (G=19,5232, d.f.=1, p<0,001) as well as united genotypes (С/C и С/T) in accordance to T/T (G=10,4657, d.f.=1; p<0,001) and united genotypes (C/T и T/T) in accordance to C/C (G=15,1896, d.f.=1, p<0,001) for the mothers of children with CCL, CCP and CCLP.Conclusion. As a result of the study, we established the association of SNP C677T of the MTHFR gene with the development of congenital cleft lip and/or palate: mothers’ T/T genotype is associated with the increased risk of giving birth to a child with CCL, CCP and CCLP (in comparison with mothers with C/C+C/T genotype): odds ratio [OR]=16,63, 95% CI: 3,86-71,71; p=0,0003 and also for mothers with genotypes (C/T+T/T) in comparison with mothers with genotypes C/C: OR=3,22, CI:1,71-6,08; p=0,0002. The amount of risk is not significant in children with CMDA for T/T genotype. So it is possible to make a conclusion about the impact of C677T of the gene MTHFR in the development of CCL, CCP and CCLP only in mother’s genotype. 


Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2019
Author(s):  
Anum Abbas ◽  
Andrea J. Zimmer ◽  
Diana Florescu

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.


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