Abdominal Solid Organ Transplant Recipients Research Articles

2107. Epidemiology and Outcomes Associated with Enterococcal Blood Stream Infection among Abdominal Solid Organ Transplant Recipients

Abstract Background Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus is an important cause of nosocomial BSI, accounting for up to 20% of BSIs in this population, with Vancomycin-resistant enterococcus (VRE) posing a particular risk. This study aims to characterize the epidemiology and outcomes of enterococcal BSIs in abdominal SOTs. Methods A retrospective, single-center, case-control study of adult abdominal organ transplant (kidney transplant (KT), liver transplant (LT), simultaneous liver-kidney transplant (SLK), pancreas transplant, or simultaneous pancreas-kidney transplant) recipients between 01/01/2016 - 07/30/2021 was conducted at Beth Israel Deaconess Medical Center. Subjects were identified and reviewed using the Organ Transplant Tracking Record, their online medical record, and Vigilanz. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. Results We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.2%). Cases were mostly LT recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14 - 43). Controls included 8 LT recipients (29%), 14 KT recipients (50%), and 6 SLK recipients (21.4%). Groups differed significantly (all p< 0.05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Most cases (n = 16; 62%) and 11 controls (39%) had received antibiotics within the month prior to transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < 0.0001) (Figure 1). There were no differences in 1-year mortality (Figure 2) between the groups. E. faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. The VRE rate was 80.8% among cases, 38.9% among all BSIs, and 4.0% among all transplants. Table 1:Demographic, Surgical, Hospitalization, and Antimicrobial Data. Baseline demographic and clinical characteristics of enterococcal BSI cases and non-enterococcal BSI controls are compared, along with transplant characteristics, transfusion requirements, surgical risk factors, hospitalization data, outcomes, and antibiotic exposures. Microbiological and resistance data are also presented. Enterococcal BSIs had lower odds of being a kidney transplant and having CKD or CKD on RRT; they had higher odds of being a liver transplant and having prior immunosuppression, steroid induction alone, reoperations, and macrolide exposure. Enterococcal BSIs had lower KDPIs, higher transfusion requirements, lower cold ischemia times, more procedures, and a shorter time to BSI (Chi-square and Fischer exact tests for categorical variables; Mann-Whitney tests for continuous variables). **Liver and simultaneous liver-kidney transplants; ***Kidney and simultaneous liver-kidney transplants; ****Reoperation within two weeks of primary closure; *****Biopsy proven acute antibody or cellular rejection within 6 months of transplant; ******ERCP stenting compared to IR stenting, among those with biliary complication. BSI – bloodstream infection; CKD – chronic kidney disease; HIV – human immunodeficiency virus; MELD – model of end stage liver disease; KDPI – kidney donor profile index; CMV – cytomegalovirus; pRBC – packed red blood cells; ERCP – endoscopic retrograde cholangiopancreatography; RRT – renal replacement therapy. Figure 1:Time to Bloodstream InfectionProbability of BSI-free survival illustrated, with enterococcal BSIs occurring significantly earlier than non-enterococcal BSIs post-transplantation (Kaplan-Meier survival analysis). BSI – bloodstream infection.Figure 2:MortalityProbability of survival, without significant difference between enterococcal and non-enterococcal BSIs. Data censored at one year of follow-up. BSI – bloodstream infection. Conclusion In our abdominal organ SOTs, enterococcal BSIs occurred early among LT recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period. Disclosures Carolyn D. Alonso, MD, Cidara Therapeutics: Advisor/Consultant|Merck: Advisor/Consultant.

Colistin (Polymyxin E) Use in Abdominal Solid Organ Transplant Recipients

Background: Patients undergoing solid organ transplantation are at a higher risk of multi-drug resistant (MDR) bacterial infections especially during the immediate post operative period. Objective: To audit the usage, dosage appropriateness and safety of colistin use in abdominal solid organ transplant recipients to treat immediate post-transplant bacterial infections. Methods: After completion of 1000 abdominal solid organ transplants at our institute, data of the transplant recipients who received colistin between October 2010 and December 2019 was extracted from the hospital health information system. Data of all microbiological culture isolates, the minimum inhibitory concentration (MIC) of colistin, appropriateness of colistin dosing and nephrotoxicity associated with colistin use was assessed. Results: Of the 1170 (732 liver and 438 renal) solid organ transplant recipients, 82 (66 liver and 16 renal) received colistin to treat posttransplant MDR bacterial infections. Nearly 60% received colistin as definitive therapy and 87.81% received colistin as combination. Mean duration of colistin therapy was found to be higher in renal than liver transplant recipients. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Colistin in combination with meropenem (36.4%) was the most commonly used dual therapy. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Overall in-hospital mortality of patients who received colistin was 43.9%. Renal impairment occurred in 28.8% of liver transplant recipients. Conclusion: Infection necessitating colistin use increases mortality by three folds in liver transplant recipients and by five percentage points in renal transplant recipients.

Letermovir conversion after valganciclovir treatment in cytomegalovirus high‐risk abdominal solid organ transplant recipients may promote development of cytomegalovirus‐specific cell mediated immunity

To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity. Adult patients were included if they received a kidney or liver transplant between 8/1/2018-12/31/20, developed symptomatic, high-level CMV viremia and were converted to letermovir 480mg daily as monotherapy after treatment with ganciclovir-derivatives for a minimum of 4weeks and had subsequent CMV cell-mediated immunity (CMI) testing via ICS assay by flow cytometry (Viracor Eurofins T Cell Immunity Panel). Seven patients met inclusion criteria; 87.5% were male and recipients of a kidney transplant. All patients were CMV high risk (D+/R-). Mean time from transplant to CMV disease was 200±91 days. Peak viral load (VL) during CMV treatment was 540,341±391,211 IU/mL. Patients received a mean of 30±24weeks (range: 4-78weeks) of therapy with ganciclovir-derivatives at induction doses prior to letermovir introduction. The median absolute lymphocyte count (ALC) at letermovir initiation was 400/μL (IQR 575) and the median VL was 51.6 (range: ND-490) IU/mL. Most patients (n=5/7, 71.4%) experienced an increase in VL 1 and/or 2weeks after conversion to letermovir. All patients had positive CMI per ICS assay after conversion. Patients received a mean of 10.3±6.9weeks of letermovir prior to having a positive result. Median ALC at positivity was 900/μL. Immunosuppression was not further reduced from initiation of letermovir to demonstration of CMV CMI. No patient had progressive replication or breakthrough disease while maintained on letermovir and three patients (42.9%) underwent antiviral withdrawal without recurrence at the last follow-up. In this case series of abdominal transplant recipients with severe or persistent CMV infection, patients developed CMV-specific CMI after conversion to letermovir monotherapy. These data suggest that using letermovir in place of valganciclovir for secondary prophylaxis may address the lack of efficacy previously seen with this approach, as well as the issues that plague antiviral withdrawal with systematic monitoring. Future prospective studies are needed to evaluate this effect in a more controlled research environment with serial CMI testing to elucidate the optimal duration of letermovir when used in this way.

Epidemiology, Susceptibility, and Risk Factors Associated with Mortality in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Abdominal Solid Organ Transplant Recipients: A Retrospective Cohort Study.

IntroductionCarbapenem-resistant gram-negative bacteria (CR-GNB) can cause life-threatening infections among abdominal solid organ transplantation (ASOT) recipients. This study aimed to investigate the epidemiology and drug susceptibility of CR-GNB pathogens and identity the risk factors associated with 90-day crude mortality of CR-GNB infections among ASOT recipients.MethodsWe retrospectively reviewed the clinical characteristics, drug resistance rate, and risk factors associated with mortality in CR-GNB infections among ASOT recipients between August 1, 2013, and August 1, 2020. The Cox regression model was performed to identify the independent risk factors for mortality.ResultsDuring the 8-year period, CR-GNB infections occurred in 153 of 1452 (10.5%) recipients, and 23 of 153 (15.0%) patients died. The most common pathogen was Acinetobacter baumannii (n = 47). The drug resistance rate of CR-GNB pathogens was relatively low to tigecycline (33.3%) and high to other categories (> 60%). There was a significant increasing trend in drug resistance to tigecycline as time went on (from 24 to 40%, P = 0.04). The independent risk factors for mortality were mechanical ventilation (hazard ratio 7.40, 95% confidence interval 2.69–20.38, P < 0.001), septic shock (hazard ratio 7.41, 95% confidence interval 2.86–19.23, P < 0.001), and platelet count < 50,000/mm3 (hazard ratio 4.00, 95% confidence interval 1.49–10.76, P = 0.006).ConclusionCR-GNB is widespread with high prevalence and mortality rates among ASOT recipients. Mechanical ventilation, septic shock, and low platelet count represent three independent risk factors related to the mortality of ASOT recipients with CR-GNB infection. We suggest that tigecycline may be used under rigorous management because of the significant increasing risk of drug resistance.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00411-z.

Impact and outcomes of primary cytomegalovirus disease in seronegative abdominal solid organ transplant recipients of cytomegalovirus unexposed donors (D-/R-).

Primary cytomegalovirus (CMV) disease in high-risk (D+/R-) abdominal solid organ transplant recipients (aSOTRs) is well described, however, little is known of primary CMV disease in low-risk (D-/R-) patients. Observational study of adult aSOTRs between 1/1/2009 and 9/1/2019 screened based on serostatus at transplant; D-/R- and D+/R- patients were included. Describe epidemiology of primary CMV in D-/R- aSOTRs. Compare infectious and transplant-related outcomes of primary CMV disease in the first 90days (early CMV) between D-/R- and D+/R-. Of 782 D-/R- aSOTRs in the study period, 13 developed CMV at any time after transplant to last follow-up. Of 671 D+/R- patients, 186 developed CMV. Early CMV disease was significantly more common in the D-/R- group (54% vs 15.6%, P=.0005) despite populations being similar demographically, including allograft subtype. D-/R- patients with early CMV disease had median viral load >100000IU/mL and 42.9% had end-organ manifestations; 71.4% required hospital admission. Immunosuppressive therapy was adjusted in 100% of patients, there was an approximately 14.3% rate of antiviral resistance and 28.6% had concomitant opportunistic infection. These findings were similar to D+/R- patients. There was no difference in risk of rejection or all-cause mortality associated with early CMV disease, however, graft loss was significantly higher in D-/R-. D-/R- aSOTRs infrequently develop CMV, however, when it occurs, they present with disease manifestations similar to and graft outcomes inferior to D+/R- with CMV. Additionally, the majority of CMV disease in D-/R- occurs in the first 90days after transplant, suggesting possible donor subclinical infection or transfusion source. The complicated course in D-/R- is likely caused by low clinical suspicion. Awareness of disease severity and aggressive upfront management may promote positive outcomes.

Safety and efficacy of catheter ablation for atrial fibrillation in abdominal solid organ (renal and hepatic) transplant recipients: A single‐center pilot experience

Atrial fibrillation (AF) is common in abdominal solid organ transplant recipients and a cause of morbidity and mortality in this population. However, the outcomes of catheter ablation (CA) in transplant recipients with AF remain unclear. This study aimed to elucidate the outcomes of CA in renal and hepatic transplant recipients. Between 2015 and 2019, 14 transplant recipients (nine with kidney transplantation and five with liver transplantation) were enrolled from among 10,741 AF patients and underwent CA at Anzhen Hospital. Another 56 patients matched by age, sex, and AF type were selected as the control group (four controls for each transplant recipient). During a mean follow-up of 30.0 ± 13.3 months after the initial procedure, 10 (71.4%) of the transplant patients, compared to 41 (73.2%) of the control patients, remained free from AF recurrence (p = 1.000). A repeated procedure was performed in one transplant patient and in six control subjects. Consequently, 11 (78.6%) of the transplant patients, compared to 46 (82.1%) of controls, were in sinus rhythm after the repeated ablation (p = .715). Notably, Kaplan-Meier analysis did not demonstrate any significant differences in the atrial arrhythmia-free rate after the initial and repeated procedure between the two groups. Vascular complications were identified in one transplant patient and two control subjects, while no life-threatening complications were observed in either group. There was no transient allograft dysfunction in transplant recipients after CA. CA is safe and effective in abdominal solid transplant recipients, and maybe an optimal therapeutic strategy for this group.

Risk Factors for Acquisition of Carbapenem-Resistant Klebsiella pneumoniae and Mortality Among Abdominal Solid Organ Transplant Recipients with K. pneumoniae Infections

BackgroundFor abdominal solid organ transplant (ASOT) recipients, infection with Klebsiella pneumoniae, particularly carbapenem-resistant K. pneumoniae (CRKP), can be life-threatening. The aims of this study were to characterize the risk factors associated with acquisition of CRKP and 90-day crude mortality among patients.Material/MethodsIn our cohort study, we retrospectively reviewed 68 K. pneumoniae-infected transplant recipients, studied their demographics, clinical manifestations, microbiology, and outcomes, and determined the risk factors associated with the occurrence of CRKP and crude mortality due to K. pneumoniae infections.ResultsSixty-eight ASOT recipients (5.4%) experienced 78 episodes of K. pneumoniae infection. Among these, 20 patients (29.4%) died. The independent risk factors associated with mortality were multiple infected organs or sites (odds ratio=22.034, 95% confidence intervals=4.348–111.653, P=0.001) and septic shock (odds ratio=27.090, 95% confidence intervals=1.841–398.512, P=0.016). Risk factors associated with acquisition of CRKP were multiple infected organs or sites (odds ratio=3.056, 95% confidence intervals=1.091–8.556, P=0.033).ConclusionsK. pneumoniae infections, especially CRKP, frequently occurred among ASOT recipients, with a high mortality rate. Multiple infected organs or sites and septic shock were predictors of crude mortality caused by K. pneumoniae infections, while CRKP infections were associated with multiple infected organs or sites. Greater efforts are needed towards improved antibiotic administration, early diagnosis and precise treatment, recognition of septic shock, and reduced length of hospitalization.

Factors Associated With Neurobehavioral Complications in Pediatric Abdominal Organ Transplant Recipients Identified Using Computable Composite Definitions.

Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels. The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created. Quaternary children's hospital with an active transplant program. Pediatric abdominal solid organ transplant recipients. None. Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52-2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41-6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49-17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication. Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.

Cardiac surgery outcomes in patients with antecedent kidney, liver, and pancreas transplantation: a meta-analysis.

Cardiovascular events are among the most common causes of late death in the transplant recipient (Tx) population. Moreover, major cardiac surgical procedures are more challenging and risky due to immunosuppression and the potential impact on the transplanted organ's functional capacity. We aimed to assess open cardiac surgery safety in abdominal solid organ transplant recipients, comparing the postoperative outcomes with those of nontransplant (N-Tx) patients. Electronic databases of PubMed, EMBASE, and SCOPUS were searched. The endpoints were: overall rate of infectious complications (wound infection, septicemia, pneumonia), cardiovascular and renal events (stroke, cardiac tamponade, acute kidney failure), 30-days, 5-years, and 10-years mortality post-cardiac surgery interventions in patients with and without prior solid organ transplantation. This meta-analysis included five studies. Higher rates of wound infection (Tx vs. N-Tx: OR: 2.03, 95% CI: 1.54 to 2.67, I2 = 0%), septicemia (OR: 3.91, 95% CI: 1.40 to 10.92, I2 = 0%), cardiac tamponade (OR: 1.83, 95% CI: 1.28 to 2.62, I2 = 0%) and kidney failure (OR: 1.70, 95 %CI: 1.44 to 2.02, I2 = 89%) in transplant recipients were reported. No significant differences in pneumonia occurrence (OR: 0.95, 95% CI: 0.71 to 1.27, I2 = 0%) stroke (OR: 0.89, 95% CI: 0.54 to 1.48, I2 = 78%) and 30-day mortality (OR: 1.92, 95% CI: 0.97 to 3.80, I2 = 0%) were observed. Surprisingly, 5-years (OR: 3.74, 95% CI: 2.54 to 5.49, I2 = 0%) and 10-years mortality rates were significantly lower in the N-Tx group (OR: 3.32, 95% CI: 2.35 to 4.69, I2 = 0%). Our study reveals that open cardiac surgery in transplant recipients is associated with worse postoperative outcomes and higher long-term mortality rates.

Clinical Manifestation, Distribution, and Drug Resistance of Pathogens Among Abdominal Solid Organ Transplant Recipients With Klebsiella pneumoniae Infections

BackgroundA Klebsiella pneumoniae infection is a life-threatening disease among abdominal solid organ transplant (ASOT) recipients. The objectives of our present work are to investigate the distribution and drug resistance of pathogens, and clinical manifestation among ASOT recipients suffering from K pneumoniae infections. MethodsThe medical records of 53 ASOT recipients with 63 episodes of K pneumoniae infections from October 1, 2013 to June 1, 2019 were reviewed according to the Declaration of Helsinki and the Declaration of Istanbul. There were no grafts from prisoners used in these 53 patients and the donors were not coerced or paid. The distribution and drug resistance of each pathogen and clinical manifestation among ASOT recipients with K pneumoniae infections were retrospectively reviewed and summarized. ResultsPrevalence and mortality of K pneumoniae infections among ASOT recipients were 4.5% and 32.1%, respectively. The origins of K pneumoniae infections were the blood (n = 21), deep wound and skin (n = 10), urinary tract (n = 9), abdomen (n = 6), and lung (n = 7). The numbers of organs from donors after cardiac death and living-related donors were 52 and 1, respectively. Twenty-nine patients had a serum creatinine level >1.5 mg/dL at the onset of K pneumoniae infections. Fifty-eight percent of K pneumoniae strains were carbapenem resistant. The resistance rate of K pneumoniae to 5 of 12 antibiotics investigated was more than 60%. The strains were relatively susceptible to meropenem, tigecycline, sulfamethoxazole, and amikacin; while there were distinctly increasing trends of resistance to meropenem and amikacin as time went on. ConclusionsThe clinical manifestation of K pneumoniae infections included elevated serum creatinine level, high carbapenem-resistant rate, and mortality. The drug-resistance rates of K pneumoniae to the most commonly used antibiotics were high with an increasing trend of resistance in recent years. Tigecycline, meropenem, sulfamethoxazole, and amikacin are recommended to treat K pneumoniae infections among ASOT recipients.

Impact of High-Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients.

To evaluate the clinical course and long-term impact of high-dose acyclovir (HD-A, 800 mg 4 times/day) cytomegalovirus (CMV) prophylaxis failure in a CMV-seropositive abdominal solid organ transplant population. Retrospective cohort study. Tertiary academic medical center. A total of 691 adults who received solid organ transplants between January 1, 2008, and June 30, 2013, without lymphocyte-depleting induction and were prescribed 3 months of HD-A prophylaxis at the time of hospital discharge. Of those patients, 54 experienced prophylaxis failure, defined as CMV detected via molecular diagnostics or on biopsy while receiving HD-A (prophylaxis failure group), and 637 did not (comparator group). Mean ± SD time to failure was 64 ± 23 days; 98% (53/54 patients) was attributable to viremia diagnosed via positive polymerase chain reaction (PCR). Of these 53 patients, 34% (18 patients) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 1531 IU/ml (interquartile range [IQR] less than 250-2947) and 4442 IU/ml (IQR less than 250-32,500); 19 (36%) had a single detectable CMV PCR. Treatment was required in 56% (30/54 patients), with a median duration of 63 days; 40% (12 patients) were treated with valganciclovir alone, and the remainder received intravenous ganciclovir. CMV disease resulted in hospitalization in 28% (15 patients). Immunosuppression was modified in 52% (28 patients). The rate of CMV recurrence after 100 days was significantly higher in the prophylaxis failure group (59% vs 13%, p<0.0001). Higher rates of rejection; higher rates of 1-, 3-, and 5-year graft failure; and higher rates of 1-, 3-, and 5-year mortality were noted in the prophylaxis failure group on univariate analysis (43% vs 30%, p=0.045; 8%, 17%, and 34% vs 4%, 12%, and 17%, p=0.006; and 6%, 17%, and 26% vs 1%, 6%, and 10%, p=0.003, respectively). Multivariate analysis demonstrated an increased risk of graft failure in the prophylaxis failure group (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1-3.1, p=0.0499) and a trend to increased mortality (HR 1.6, 95% CI 0.83-3.1, p=0.16). Prophylaxis failure with HD-A was mostly limited to mild viremia; however, it was associated with significantly reduced long-term graft survival, likely reflecting the negative impact of CMV viremia.

Cardiac Surgery Outcomes in Abdominal Solid Organ Transplant Recipients

Cardiovascular disease is a cause of morbidity and mortality in organ transplant recipients. Cardiac surgery after organ transplantation is not uncommon in this population. We evaluated 30-day outcomes and long-term survival of abdominal transplant recipients undergoing cardiac surgery at our institution. In all, 138 patients with previous kidney, kidney-pancreas, and liver transplants underwent cardiac surgery from 2000 to 2016. Propensity score (ratio 1:3) matched 115 abdominal transplant with 345 patients undergoing cardiac surgery without a history of abdominal transplant. They were matched for type and year of cardiac surgery, age, sex, body mass index, history of diabetes mellitus, and creatinine level before cardiac surgery. Median time from abdominal transplant to cardiac surgery was 7 years (interquartile range, 3 to 12 years). Perioperative variables, including surgery and cardiopulmonary bypass time, aortic cross-clamp and intubation time, and intensive care unit stay did not differ between the groups. Hospital length of stay and rate of 30-day hospital readmissions did not differ between the groups. Patients with abdominal transplants had more strokes (4% versus 0.6%; p= 0.005) within 30 days after surgery. There were no differences in renal failure, bleeding, site infections, atrial fibrillation, and pneumonia between the groups. Five patients (4%) died within 30 days after surgery in the abdominal transplant group (4 kidneys, 1 liver, 0 kidney-pancreas), and 7 patients (2%) died in the nontransplanted group (p= 0.24). Previous history of abdominal transplant is associated with an increased 30-day incidence of stroke after cardiac surgery. Abdominal transplant does not affect 30-day mortality after cardiac surgery, whereas long-term survival is significantly reduced. Regular patient follow-up and prevention and early treatment of postoperative complications are key to patient survival.

Ganciclovir-Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature.

Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins, and leflunomide.

Fosfomycin tromethamine for the Treatment of Cystitis in Abdominal Solid Organ Transplant Recipients With Renal Dysfunction.

Urinary tract infection (UTI) after abdominal solid organ transplantation (SOT) is associated with significant morbidity and mortality. Fosfomycin tromethamine (FOS), a uroselective antibiotic, is FDA approved for uncomplicated UTIs in women and is used off-label for complicated UTIs and prostatitis in men. Literature supporting the use of FOS in the SOT population is limited, and efficacy is questioned in the setting of renal dysfunction. To evaluate the success of FOS for the treatment of cystitis in SOT patients with renal dysfunction. This was a single-center, retrospective study using medical records. SOT recipients receiving at least 1 dose of FOS for treatment of cystitis between January 1, 2009, and April 30, 2015, were included. Treatment outcomes were analyzed with respect to renal function. A total of 76 courses of FOS were identified in 64 patients. The renal dysfunction arm (creatinine clearance [CrCl] < 40 mL/min) included 33 patients with 39 FOS courses; the normal renal function arm (CrCl ≥ 40 mL/min) included 31 patients with 37 FOS courses. Mean CrCl was 23.3 ± 9.7 mL/min for the renal-dysfunction group and 65 ± 29.3 mL/min for the normal renal function group ( P < 0.01). No significant difference in treatment success was noted between CrCl <40 mL/min and CrCl ≥40 mL/min (31 [80%] vs 34 [92%], P = 0.12) in a unilateral analysis. After adjusting for confounders in a multivariable analysis, there was no difference in the risk of failure between CrCl <40 mL/min and CrCl ≥40 mL/min groups ( P = 0.70). FOS appears to be successful for the treatment of cystitis in SOT recipients in the setting of renal dysfunction.

Factors influencing mortality in abdominal solid organ transplant recipients with multidrug-resistant gram-negative bacteremia

BackgroundAlthough multidrug-resistant (MDR) gram-negative bacteremia (GNB) has been recognized as an important cause of morbidity and mortality among abdominal solid organ transplant (ASOT) recipients, there are no data on its prognostic factors after an interim standard definition of MDR was proposed in 2012. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in ASOT recipients with MDR GNB.MethodsWe performed a retrospective, double-center analysis of ASOT patients with MDR GNB over a 13-year study period. Univariate and multivariate analyses were performed to identify the risk factors for mortality.ResultsDuring the observational period, 2169 subjects underwent ASOT. Ninety-nine episodes of MDR GNB were diagnosed in 91 (4.6%) ASOT recipients, with a predominance of E.coli (29 isolates, 29.3%) and A.baumanii (24 isolates, 24.2%). The median age of these 91 recipients was 45 years (interquartile range 35–54). Mortality after the first episode of MDR GNB was 39.6% (36 deaths). The univariate analysis identified the following variables as predictors of MDR GNB-related mortality: lung focus (P = 0.001),nosocomial origin (P = 0.002), graft from donation after cardiac death or deceased donors (P = 0.023), presence of other concomitant bloodstream infection (P < 0.001), temperature of 40 °C or greater at the onset of MDR GNB (P = 0.039), creatinine > 1.5 mg/dl (P = 0.006), albumin < 30 g/L (P = 0.009), platelet count < 50,000/mm3 (P < 0.001), and septic shock (P < 0.001). In the multivariate logistic regression analysis, septic shock (odds ratio (OR) = 160.463, 95% confidence interval (CI) = 19.377–1328.832, P < .001), as well as creatinine > 1.5 mg/dl (OR = 24.498, 95% CI = 3.449–173.998, P = 0.001), nosocomial origin (OR = 23.963, 95% CI = 1.285–46.991, P = 0.033), and presence of other concomitant bloodstream infections (OR = 27.074, 95% CI = 3.937–186.210, P = 0.001) were the variables associated with MDR GNB-related 30-day mortality.ConclusionsMDR GNB was associated with high morbidity and mortality in ASOT recipients, with a predominant causative organisms being E.coli and A.baumanii. Nosocomial origin, as well as presence of other concomitant bloodstream infections, increased creatinine level and septic shock were the main predictors of MDR GNB-related 30-day mortality.

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Introduction: Very high doses of narcotics and benzodiazepines are often needed for sedation and analgesia after extensive abdominal surgery in children, with the potential for excessive sedation, prolonged ventilation and withdrawal. Hypothesis: We hypothesized that neuromuscular blockade used as an adjunct to sedation and analgesia during the first postoperative day would decrease need for treating withdrawal without increasing ventilator days and PICU length of stay (LOS). Methods: Starting in July 2011, we gave a weakening dose of atracurium during the first 24 hours after surgery in addition to usual fentanyl, benzodiazepines, morphine and dexmedetomidine to pediatric single or multiple abdominal organ transplant recipients (Group P, n=12). Cumulative narcotic doses given during the first 48 hrs and need for methadone-lorazepam on transfer out of the PICU were compared with a non-paralyzed cohort (Group NP, n=12) from the previous year. Patients with early surgical complications were excluded from analysis. Results: There were no differences in demographics including age, diagnosis and type of transplant. For Group P vs. Group NP, median fentanyl used (µg/Kg/day) was 46.0 (29.7-69.7) vs 24.6 (24.1-29.6) (P= 0.036, Mann-Whitney). Methadone-lorazepam treatment on transfer out of the PICU was less common in Group P (P= 0.046, Fisher’s exact test) with no increase in ventilator days or PICU-LOS as compared to Group NP. Conclusions: We conclude that the use of brief, early post-operative paralysis reduces narcotic dependence without prolonging mechanical ventilation in pediatric abdominal solid organ transplant recipients.

Cardiac surgical outcomes in abdominal solid organ (renal and hepatic) transplant recipients: a case-matched study

This study aims to investigate the outcomes of cardiac surgery in patients with abdominal solid organ transplants and to compare them with the case-matched population undergoing cardiac surgery. Data from all transplant recipients abdominal solid organ transplant (ASOT) N = 36 (30 renal and 6 hepatic) who underwent cardiac surgery in a single centre during the period from January 1997 to December 2010 were collected from hospital transplant registries and the cardiac database. The transplant recipients were case matched (CM) with 104 patients in terms of the variables of age, sex and the type of cardiac surgery. Follow-up data were obtained from medical records and by a set of questionnaire through telephonic interviews. Follow-up times were 4.5 ± 3.2 and 3.9 ± 3.2 years in the transplant and CM groups, respectively. Follow-up in the transplant group was 100%. There was no 30-day mortality in the transplant group. Thirty-day combined major morbidities were 9% in the matched group vs 11% in the transplant patients (P = 0.6). Median length of stay was 6 days (inter-quartile range, IQR 5.9) for ASOT vs 5 days (IQR 4.6) for CM (P < 0.01). New dialysis was 8.3% in transplant patients compared with 0.96% in the matched population, while infection was 16.66 vs 0.42% in the CM cohort. There was no allograft failure/dysfunction at the time of death or latest follow-up. Late deaths were 8 of 36 (22%) in ASOT vs 6 of 104 (6%) in CM. Infection (63%) was the most frequent major cause of death in transplant patients. One-, 2-, 5- and 10-year survivals for ASOT vs CM were 94, 88, 80, 59 vs 99, 99, 91, 85%, respectively. Multivariate predictors of mortality were increasing age (hazard ratio, HR 1.1, 95% confidence interval, CI 1.04-1.18; P = 0.003) and solid organ transplantation (HR 3.44, CI 1.19-9.98; P = 0.023). Cardiac surgery can be performed in patients with abdominal solid organ tranpslant recipients with acceptable early morbidity and mortality. However, long-term survival in transplant patients is poor. Infection remains the most common cause of death.

Cardiac Surgical Outcomes in Abdominal Solid Organ (Renal and Hepatic) Transplant Recipients: A Case Matched Study

Background: Cardiovascular disease is a common cause of mortality and morbidity after abdominal solid organ transplants (ASOT). We studied the long-term outcomes after cardiac surgery in patients with functioning ASOT and compared them with a case matched (CM) population.