#74: Development of a Solid-Organ Transplant-Specific Antibiogram in a Tertiary Pediatric Hospital in Canada

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
T Kitano ◽  
M Science ◽  
N Nalli ◽  
K Timberlake ◽  
U Allen ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lower Sensitivity ◽  
Solid Organ ◽  
Pediatric Hospital ◽  
Post Transplant ◽  
Significant Difference ◽  
Organ Specific ◽  
Wide Population

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 <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 < 0.001), cefotaxime (59% vs. 88%; P < 0.001), ciprofloxacin (71% vs. 87%; P = 0.007) and cotrimoxazole (41% vs. 69%; P < 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.

scholarly journals Does Post-Transplant Cytomegalovirus Increase the Risk of Invasive Aspergillosis in Solid Organ Transplant Recipients? A Systematic Review and Meta-Analysis

2021 ◽  
Vol 7 (5) ◽  
pp. 327
Author(s):  
Nipat Chuleerarux ◽  
Achitpol Thongkam ◽  
Kasama Manothummetha ◽  
Saman Nematollahi ◽  
Veronica Dioverti-Prono ◽  
...  
Keyword(s):  
Systematic Review ◽  
Invasive Aspergillosis ◽  
Meta Analysis ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Effect Estimate ◽  
Solid Organ ◽  
Post Transplant ◽  
Cmv Disease ◽  
The Impact

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.

Influenza B Virus Infection in Pediatric Solid Organ Transplant Recipients

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 225-229
Author(s):  
Teri Jo Mauch ◽  
Tim Myers ◽  
Clifford E. Kashtan ◽  
Susan Bratton ◽  
Elliot Krane ◽  
...  
Keyword(s):  
Virus Infection ◽  
Clinical Symptoms ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Influenza B Virus ◽  
Influenza B ◽  
Solid Organ ◽  
Normal Children ◽  
Post Transplant ◽  
B Virus

Objective. Influenza B virus causes epidemic infection in normal children, but only one case of infection in an immunocompromised solid organ transplant (SOT) recipient has been reported. Characterization of the clinical course of influenza B virus infection in pediatric SOT recipients may increase the utilization of preventive and therapeutic interventions by pediatricians caring for these immunocompromised children. Design. Retrospective chart review of patients whose respiratory viral cultures yielded influenza B from January 1989 through March 1992. Patients. Twelve pediatric SOT recipients with influenza B virus infection were identified. These included five renal, four hepatic, and three cardiac allograft recipients, ranging from 19 months to 17 years 9 months of age (median 6 years 2 months). The post-transplant interval ranged from 6 weeks to 4 years 6 months (average 26.7 months). No patient had been immunized against influenza. Exposure histories were documented for eight children; five of these occurred in the hospital. Results. Clinical symptoms included fever (12/12), respiratory (11/12), or gastrointestinal complaints (8/12). Five patients had neurologic involvement; one died of uncal herniation. Ten children were hospitalized (median duration, 3 days; range, 2 to 79 days). Two patients (post-transplant interval, 3 to 8 months) required mechanical ventilation, and one of these received aerosolized ribavirin. Three children had concurrent allograft rejection. Conclusions. Influenza B infection is potentially life-threatening in pediatric SOT recipients. We recommend annual immunization of pediatric SOT recipients, their household contacts, and health care workers. Prospective studies are needed to evaluate the efficacy of influenza vaccination in pediatric SOT recipients.

Cardiac Complications Following Allogeneic Bone Marrow Transplantation: Evaluation of Risk Factors, Outcomes and Enhanced Screening for At Risk Populations.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3070-3070
Author(s):  
Michael Henry ◽  
Rong Guo ◽  
Mala Parthasarathy ◽  
John Lopez ◽  
Patrick Stiff
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
High Risk ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Low Risk ◽  
Solid Organ ◽  
Cardiac Events ◽  
Post Transplant ◽  
Risk Patients

Abstract Abstract 3070 Life-threatening cardiac events following allogeneic bone marrow transplants (BMT) are not uncommon at 5–12.5% of patients. While BMT programs perform screening EKGs and ejection fraction measurements, solid organ transplant centers follow a risk stratification screening algorithm to assess for coronary artery disease (CAD) which includes stress tests and as indicated, angiography in those with 2 or more risk factors. It is currently unknown whether this algorithm should be applied in the BMT setting. Methods: We performed a retrospective review of 296 patients who underwent allogeneic BMT at Loyola University Medical Center 2007–2011, to assess cardiac events using the solid organ transplant advanced screening criteria: age over 60 or over 40 with peripheral vascular disease or diabetes and then divided patients into low risk (one CV risk factor) and high risk groups (greater than one CV risk factor). Risk factors included age, hypertension, diabetes, smoking, family history of CAD, and obesity according to the Framingham risk assessment score for CAD. Cardiac events during the first year post-transplant were recorded including CHF, myocardial infarction (MI), and symptomatic arrhythmias. One hundred day and 1-year Kaplan-Meier survival for high and low risk patients were determined and curves compared by log-rank tests. A multivariate analysis of the various prognostic factors was performed using the Cox regression model. Results: Of the 296 total allografts, 116 patients (39%) fit the solid organ transplant criteria for advanced screening; 62% were male (n = 72) and the mean age was 60.6 (range 40–72). Graft source was evenly distributed between siblings (42%), unrelated (39%) and cord blood (28%). Acute myeloid leukemia was the most common indication for BMT at 40%, followed by MDS (21%), non-Hodgkin lymphoma (16%), and CLL (10%). Of the 116, 21 were considered low risk (1 risk factor), while 95 were high risk (2+ risk factors). Low risk and high risk groups did not differ in disease type (p = 0.43), graft source (p = 0.81), or graft type (p = 0.54). Surprisingly, both high and low risk patients had a similar incidence of cardiac events of 36% and 48%, respectively. This correlated to comparable 100-day and 1 year survival rates. To determine the importance of cardiac complications on outcome and whether there were other risk factors for complications we analyzed those with a complication. Forty-four cardiac events occurred in the first year after transplant in 38 (33%) patients. Cardiac events included arrhythmias (n = 33), new onset CHF (n = 6), and MI (n = 5). Median time to event was 16 days post-transplant. Symptomatic arrhythmias included atrial fibrillation (n = 27, 82%), supraventricular tachycardia (n = 5, 15%) and sustained ventricular tachycardia (n =1, 3%). Median age for patients with cardiac events was 62.7 years, compared to 59.6 for patients who experienced no cardiac events (hazard ratio estimate: 1.076; p = 0.02). As compared to patients with no post-transplant cardiac events, both the 100 day and 1 year survival rates of patients with cardiac events were lower with one year survival of 21% vs. 63% (p < 0.0001). Evaluating risk factors, 3 were significant: donor source with MUD donors the highest hazard (p = 0.04); age, with cardiac events occurring at a rate twice as high in patients greater than age 60 (n = 27, 36.5% vs. n = 6, 19.4%), and with all five cases of myocardial infarction and 5/6 new CHF diagnoses occurring in patients aged 60 or greater; and patients with a history of atrial fibrillation demonstrated a higher probability of developing a cardiac event post-transplant (p = 0.02). Conclusions: In this analysis, we saw a much higher incidence of post-BMT cardiac events (33%) than previously reported, although we focused only on at risk patients using the solid organ screening algorithm (pts > 40 with significant risk factors or all pts > 60). As mortality rates at 100 day and 1 year are higher for patients who suffer a post-BMT cardiac event, and only graft source, age and prior atrial fibrillation marked patients at a very high risk, this data indicates that it is appropriate to investigate prospectively the solid organ transplant algorithm in all allogeneic BMT patients > age 40, with low cardiac risk or any patient > 60 with stress tests and as indicated, cardiac catheterization. Whether this will decrease events and thereby improve survival remains to be determined by prospective studies. Disclosures: No relevant conflicts of interest to declare.

DA-R-EPOCH in Post Transplant Lymphoproliferative Disorders (PTLD) and EBV-Positive High Grade B-Cell Lymphomas with Rearrangements of MYC and BCL2 (HGBL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1875-1875
Author(s):  
Patrick D. Ford ◽  
Alexandra E. Kovach ◽  
John P. Greer ◽  
David S. Morgan ◽  
Mahsa Sharifi Talbott ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Organ Transplant ◽  
B Cell Lymphoma ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Advisory Committees ◽  
Free Survival ◽  
Post Transplant ◽  
Number Of Patients

Abstract Introduction: Immunotherapy with rituximab alone or in combination with sequential chemotherapy such as CHOP, in addition to a reduction in immunosuppression (IST), has been shown to be effective in achieving long-term, disease-free survival in patients with B-cell PTLD. We have recently observed an increased incidence of HGBL in patients receiving IST following solid-organ transplant. Intensive induction regimens (ex: DA-R-EPOCH) in non-transplant HGBL has been associated with improved complete responses. Intensive regimens have not been previously evaluated in patients with PTLD. The aim of this study is to compare the tolerability of DA-R-EPOCH to R-CHOP in post-transplant patients with HGBL. Methods: Patients treated with either DA-R-EPOCH or R-CHOP were included in this study following IRB approval. Eligible patients were ≥18 years, had biopsy-confirmed B-cell PTLD, and were treated with at least one cycle of DA-R-EPOCH or R-CHOP. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), toxicities, and hospitalizations due to treatment-related toxicities. Statistical analysis was performed using SPSS.22 software Results: Sixty-three patients had biopsy-confirmed PTLD. Of these, 26 met inclusion criteria. Among these 26 patients, 19 (73.1%) were men; median age was 57 years (18-75 years); and transplants included 3 (11.5%) lung, 4 (15.4%) heart, 9 (34.6%) kidney, 8 (30.8%) liver, 2 (7.7%) pancreas, and 1 (3.8%) stem cell. All patients were receiving IST at the time of diagnosis of PTLD. Pathology reports found that 24 (92.3%) had diffuse large B-cell lymphoma (DLBCL)-like PTLD, and 11 (57.9%) had EBV-positive disease. HGBL was observed in 10 (38.5%) patients. Seven patients received DA-R-EPOCH, and 19 received R-CHOP. Baseline characteristics were similar between treatment groups. There was a significantly higher number of patients with HGBL in the DA-R-EPOCH arm compared with the R-CHOP arm (100% [7/7] vs. 15.8% [3/19]; 95% CI, -0.01-1.00; p=0.001). The median number of cycles administered was not significantly different between the groups (4.6 cycles vs. 5 cycles; 95% CI, 4.33-6.07; p=0.645). Dose intensification occurred in 8 of 32 cycles for patients who received DA-R-EPOCH. The median follow-up time for patients treated with DA-R-EPOCH was shorter (10 months) than for patients treated with R-CHOP (29 months). PFS was not found to be significantly different between the DA-R-EPOCH and R-CHOP arms (10.4 months vs. 61.4 months; 95% CI, 1.80-18.99; p=0.31). Patients with EBV-positive disease had inferior PFS compared with EBV-negative disease (7.37 months vs. NR; 95% CI, 1.02-10.2; p=0.046). In addition, OS, neutropenia, thrombocytopenia, hospitalizations, and hospitalizations due to febrile neutropenia were not significantly different between groups, though trends toward higher rates of grade 3 or 4 neutropenia, thrombocytopenia, and hospitalizations was observed in the DA-R-EPOCH group. Conclusion: To our knowledge, this is the first study evaluating the role of intensive induction therapy in patients with HGBL with MYC and BCL2 rearrangements observed in solid organ transplant recipients. In patients with PTLD, DA-R-EPOCH is a well-tolerated regimen with concurrent taper in IST. However, this strategy may not overcome the poor prognosis of HGBL. Dose adjustments beyond level 2 were limited by cytopenias. Figure Figure. Disclosures Reddy: KITE: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees; INFINITY: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Incidence and Outcomes of Post-Transplant Lymphoproliferative Disease after 5365 Solid Organ Transplants over a 20 Year Period at 2 UK Transplant Centres

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 888-888
Author(s):  
Anna Santarsieri ◽  
Andrew Butler ◽  
William Gelson ◽  
Stephen Pettit ◽  
John F Rudge ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Lymphoproliferative Disease ◽  
First Year ◽  
Solid Organ ◽  
Line Treatment ◽  
First Line ◽  
Post Transplant

Abstract Background: Post-transplant lymphoproliferative disease (PTLD) confers a high morbidity and mortality in a vulnerable population. We present the epidemiology and outcomes of PTLD in a large UK cohort of solid organ transplant (SOT) recipients who were transplanted over a 20-year period. Methods: This is a retrospective study of 5365 SOT recipients who had their first transplant between 2000 and 2021 at two UK transplant centres (Addenbrooke's Hospital and Papworth Hospital). We reviewed the records of all patients and found 142 who subsequently developed PTLD. For each type of transplant, we calculated the incidence rate of PTLD and cumulative incidence using a competing risk of death model. Survival was compared with the age-adjusted life expectancy of the UK population using the National life tables and a landmark analysis was performed to compare overall survival (OS) of PTLD patients from the date of diagnosis with the background survival of the transplant population. To compare treatment outcomes, a subset of 90 cases of monomorphic PTLD, DLBCL subtype were identified. 66 were treated with first-line Rituximab monotherapy and 24 received first-line R-Chemotherapy. Demographics, treatment response, and survival data were analysed with univariate and multivariate analysis to identify covariates associated with death in the first year post diagnosis of PTLD. Results: With a median follow-up time of 5.3 years, 142 of 5365 solid organ transplant recipients have developed PTLD (56/1965 kidney, 22/1428 liver, 12/327 simultaneous kidney-pancreas (SPK), 21/113 multivisceral (MVT), 10/778 heart, 15/503 bilateral lung, 3/148 single lung and 3/85 heart and lung). The incidence rate of PTLD was highest in the first year post-transplant in lung and MVT recipients. Cumulative incidence (shown in Figure 1) was 18% at 5 years post-MVT and 1-3% at 5 years following the other SOT types. Cumulative incidence was lowest for liver and heart transplants and was 10% at 20 years post-kidney transplantation. Median OS following SOT was 16 years which is significantly reduced compared with the age-adjusted UK population. There is a relatively high early mortality rate following diagnosis of PTLD and only patients surviving two years post diagnosis regained a similar longer-term survival to the non-PTLD SOT cohort. Treatment with rituximab monotherapy (RM) is now a standard of care for monomorphic PTLD 1. Outcomes for monomorphic patients were compared between those treated with RM (n=66, median follow-up 2.2 y) and R-Chemotherapy (n=24, median follow-up 5.2 y). The two groups were well matched for age and IPI. Of the 66 RM patients, 22 (33%) achieved complete remission with RM and required no further treatment. A further 18 (27%) patients achieved remission following further treatment with chemotherapy/surgery/CTL. 6/66 (9%) patients died of progressive disease (PD), 9/66 (14%) died pre-remission of non-PTLD causes and 11/66 (17%) died in remission of unrelated causes. In the R-Chemotherapy group, 22 patients received R-CHOP and 2 received R-CVP (n=24). 8 (33%) patients are alive and in remission after first line treatment and a further 3 patients (13%) after second line treatment. 2/24 (8%) patients died of PD, 4/24 (17%) died pre-remission of non-PTLD causes and 7/24 (30%) died post-remission of unrelated causes. There is no significant difference in OS between the two groups. Only a minority of deaths were due to PD and death from non-lymphoma causes pre and post remission remain considerably higher than non-PTLD SOT patients up to 2 years post treatment (Figure 1). Multivariate analysis of all 90 monomorphic PTLD patients identified IPI3+ as the strongest pre-treatment variable associating with inferior 1 year OS. Interestingly IPI3+ did not retain this significance when R-chemo patients were analysed alone. Conclusion: With this large SOT dataset we have mapped the cumulative incidence of PTLD over a 20 year period and highlight transplanted organ-specific differences in PTLD incidence over time. Treating monomorphic DLBL patients first-line with RM rather than R-chemotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes pre- and post-treatment remains high with both treatment approaches, with poor OS compared with age-matched non-PTLD SOT recipients. 1Trappe et al. Lancet Oncol; 2012 13(2):196-206 Figure 1 Figure 1. Disclosures Santarsieri: Janssen: Honoraria. Uttenthal: Roche: Other; Takeda: Other; Jazz: Other. Follows: Janssen, Abvie, Roche, AZ: Other.

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