With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period.
BACKGROUND:The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality.METHODS:A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association.RESULTS:Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16).CONCLUSIONS:MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.
Background Risk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact of daptomycin-resistant Enterococcus (DRE) in this patient population. Methods We conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within 1 year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest. Results We identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total intensive care unit days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within 1 year of transplantation (adjusted odds ratio [aOR], 2.648; 95% CI, 1.025-6.840; P = .044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR, 30.62; 95% CI, 10.087-92.955; P < .001). Conclusions In this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared with VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.
Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. A retrospective cohort study was performed at three transplant centers. Exposed donors were those with “recent IDU” (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06–12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71–1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29–1.51, p = .33).
Abstract Background Graduate medical education programs shifted to an all-virtual recruitment in 2020. There is little published on the impact of this shift on the demographics of applicants, particularly in a field such as infectious disease where there are typically fewer applicants than available spots. Program directors were forced to make a radical change to their typical recruitment process. This study illustrates a single-center experience with virtual ID fellowship interviewing. Methods Using the Program Director Work Station on Electronic Residency Application Service (ERAS), we reviewed our program specific data from 2018-2021. We extracted the total number of applicants, the self-identified race/ethnicity of the applicants, their medical school type (US MD grad, DO grad, Non-US grad), their sex, and their location. We used simple descriptive statistics to identify trends and comparisons from in-person interviewing (2018 and 2019) and virtual interviewing (2020 and 2021). Results The number of virtual ID fellowship applicants to our program increased in 2021 by 24% compared to in-person applicants in 2019 (123 vs. 99). This exceeds what a program would expect from the 13% nation-wide increase in ID applicants in 2021 as there were a record 404 total applicants compared to 356 total applicants in 2019 We also saw an increase in Black or African American applicants; 13 Black applicants in 2021 compared to 2 Black applicants in 2019. We saw a stable rate of applicants who self-identified Hispanic, Latino, or of Spanish origin; 18 in 2019 and 17 in 2021. as Notably, we also saw an increase in geographic diversity of our applicants as we drew applicants from 22 states in 2019 (Figure 1a) and 35 states in 2021 (Figure 1b). Additionally, in 2020 we matched two applicants from geographically distant states (Ohio and Colorado) and in 2021 we matched one (Mississippi). Figure 1aFigure 1b Conclusion Virtual interviewing was advantageous for our infectious disease fellowship program at Temple University. We saw a 24% increase in applicants, had more Black applicants and more geographic diversity in our applicants. Furthermore, we were able to recruit these applicants into matched fellows. Disclosures All Authors: No reported disclosures.
Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship.
Abstract Background With the ongoing opioid epidemic in the US, there has been an increase in the proportion of deceased organ donors with a history of injection drug use (IDU), raising concern for additional infectious risks to transplantation.We sought to determine how recent IDU among deceased organ donors impacted donor culture results. Methods A retrospective cohort study was conducted at four transplant centers in Philadelphia between 1/1/2015 and 6/30/2016. All deceased organ donors who donated ≥ 1 organ to one of the centers were included. Exposed donors were those with a recent history of IDU (defined by use in the prior 12 months based on donor chart review). Unexposed donors were those with no recent history of IDU. The primary outcome was any positive donor culture (taken during the terminal hospitalization or at the time of organ procurement) for bacteria or Candida. Multivariable logistic regression was used to determine the association between recent IDU and donor culture positivity. Secondarily, the association between donor IDU and isolation of (1) a multidrug-resistant organism (MDRO) on culture, (2) Staphylococcus aureus on culture, (3) Candida on non-respiratory culture, and (4) bacteria or Candida on blood culture were determined. Results Of 394 total donors, 66 (17%) had a history of recent IDU and 343 (87%) had at least one positive donor culture. On multivariable analysis, recent IDU was associated with significantly increased odds of having at least one positive donor culture (aOR 3.6, 95% CI 1.1-11.9, P=0.04) and Candida on non-respiratory culture (aOR 2.6, 95% CI 1.1-6.2, P=0.03). However, recent IDU was not significantly associated with increased odds of MDRO on culture (OR 0.90, 95% CI 0.41-1.93, P=0.79), S. aureus on culture (OR 1.35, 95% CI 0.79-2.28, P=0.27), or positive blood culture (OR 0.79, 95% CI 0.32-1.95, P=0.60). Conclusion Donors with a recent history of IDU are more likely to have bacteria or Candida identified on cultures taken during their terminal hospitalization or at organ procurement. This increase does not appear to be driven by MDROs, S. aureus, or bloodstream infections but rather by Candida isolated from non-respiratory sites, potentially alleviating some fears surrounding the acceptance of solid organs from donors with a history of recent IDU. Disclosures Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB)) Emily Blumberg, MD, Amplyx (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))Hologic (Research Grant or Support)Merck (Grant/Research Support, Other Financial or Material Support, Member of Scientific Advisory Committee)Takeda (Research Grant or Support, Other Financial or Material Support, Member of Scientific Advisory Committee) Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Judith A. Anesi, MD, MSCE, Nothing to disclose
The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.
Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with a roadmap for addressing common contemporary remediation challenges.
Abstract Background Clostridium difficile infection is a serious and common illness affecting almost 500,000 people in the United States each year. Solid-organ transplant recipients are at increased risk for this infection, with lung transplant patients being at the highest risk. Temple University Hospital (TUH) in Philadelphia has performed the most lung transplants in the United States over the last 2 years. Methods A retrospective case–control study was performed to identify patients diagnosed with C. difficile following lung transplantation at our institution between January 1, 2014 and April 30, 2018 (N = 35). We randomly selected control patients (N = 35) who had lung transplantation performed during this time but did not develop C. difficile infection. The study objectives were to characterize risk factors that are associated with C. difficile infection in lung transplant recipients and compare clinical outcomes in recipients with and without C. difficile. Statistical analysis was performed using Epi Info (CDC, Atlanta GA). Results The average age was 62.4 years, 64.7% were male, 75% were white and 69.1% of transplants were performed for underlying idiopathic pulmonary fibrosis. 52.9% of patients had “non-severe” C. difficile infection as defined by the 2018 Infectious Disease Society of America guidelines. Patients with C. difficile infection were more likely to have been treated for cytomegalovirus (CMV) viremia (OR 8.2, 95% CI 2.4–28.2, P = 0.0006) and were more likely to have received third- to fifth-generation cephalosporins (OR 4.0, 95% CI 1.4–11.2, P = 0.01) and/or carbapenems (OR 3.7, 95% CI 1.4–9.9, P = 0.02). Patients with C. difficile infection were more likely to experience multiple hospitalizations when compared with C. difficile-negative patients (3.6 vs. 8.4, P = 0.003). 22 of the 68 evaluable patients died during the study period, 9 of whom had C. difficile infection (P = NS). Conclusion Patients who received lung transplants and developed C. difficile infection were more likely to be treated for CMV viremia, receive antibiotics including cephalosporins and/or carbapenems and require repeat hospitalizations when compared with control patients who did not develop C. difficile infection following transplant. Disclosures All authors: No reported disclosures.
Abstract Background Transplant guidelines recommend exercising caution when considering organs that may be infected or colonized with multidrug-resistant organisms (MDROs) and treating the organ recipient with perioperative antibiotics active against the donor MDRO. Unfortunately, donor MDROs are often identified only after transplantation. We developed a clinical prediction tool to stratify donors’ MDRO risk at the time of donor evaluation. Methods A retrospective cohort study was conducted at four transplant centers in Philadelphia between January1, 2015 and June 30, 2016. All deceased organ donors who donated ≥1 organ to one of the centers were included. Multivariate logistic regression was used to determine predictors of donor MDROs, including methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci, extended-spectrum cephalosporin-resistant (ESC-R) or carbapenem-resistant Enterobacteriaceae, multidrug-resistant (MDR) P. aeruginosa, or MDR Acinetobacter species. Manual forward selection was utilized to maximize the area under the receiver operating characteristic curve (AUC). A scoring system was developed based on the odds ratios for each covariate. Internal validity was assessed using the Hosmer–Lemeshow statistic, specificity, and negative predictive value (NPV). Results Of 440 total donors, 62 (14%) grew MDROs on culture. The majority were MRSA (40) or ESC-R Enterobacteriaceae (20). The most parsimonious model that predicted donor MDROs included: a terminal hospitalization ≥ 7 days (1 point), ≥ 2 antibiotics administered during the terminal hospitalization (1 point), receipt of extracorporeal membrane oxygenation (ECMO) (1 point), and presence of opacities on donor chest imaging concerning for lower respiratory tract infection (2 points). With this scoring system, the maximum attainable score is 5; any donor with a score of ≥ 2 points would be considered high risk for an MDRO, with an AUC of 0.71, specificity of 99%, and NPV of 86%. The Hosmer–Lemeshow P = 0.68. Conclusion The risk of an MDRO among deceased organ donors can be predicted using the above scoring system. This tool will inform decisions about organ utilization and perioperative prophylaxis for solid-organ transplant recipients. Disclosures All authors: No reported disclosures.
BACKGROUND:Bronchial stenosis is a known complication of lung transplantation, but there are limited data regarding whether transplant recipients with bronchial stenosis develop more infectious complications than those without bronchial stenosis.METHODS:We conducted a retrospective single-center observational cohort study between January 1, 2011 and September 29, 2016 of 35 lung transplant recipients diagnosed with bronchial stenosis and a random sample of 35 lung transplant recipients without bronchial stenosis. Data collected included donor/recipient demographic and anatomic information, respiratory cultures, episodes of respiratory infections diagnosed using CDC-NNIS criteria, hospitalizations, and 1-year all-cause mortality. Patients were followed up to 1 year after transplant.RESULTS:Bronchial stenosis occurred at a median of 54 days post-transplant (range 5-365 days). Bronchial stenosis patients spent more time in the hospital (87.4 vs 46.8 days, P = 0.011) and had more total hospitalizations (4.54 vs 2.37, P < 0.01) than their counterparts. The relative risk of pneumonia among cases vs controls was 4.0 (95% CI 2.2-7.3, P < 0.01); for purulent tracheobronchitis the relative risk was 3.1 (95% CI 1.6-6.1, P < 0.01). Patients with bronchial stenosis were significantly more likely to have respiratory cultures growing Staphylococcus aureus (RR 5.0; P = 0.001) and Pseudomonas aeruginosa (RR 2.1, P = 0.026). Mortality within the first year following transplant was equal in both the groups (14.3% vs 14.3%).CONCLUSIONS:There was no significant increase in 1-year mortality for lung transplant patients who developed bronchial stenosis. However, bronchial stenosis patients had significantly higher risks of pneumonia and tracheobronchitis, and spent more days in the hospital than those without bronchial stenosis.
BACKGROUND:Our case series describes three patients who have received single-lung transplantations for idiopathic pulmonary fibrosis (IPF) that develop cytomegalovirus (CMV) disease and hypoxemic respiratory failure with radiographic opacification of the native lung and sparing of the allograft.RESULTS:Hypoxemia resolved with treatment and with resolution of CMV viremia. Viral infections causing IPF exacerbations have been described in the literature, however, pulmonary CMV disease in single-lung transplant recipients has typically been observed as pneumonitis of the allograft.CONCLUSIONS:These clinical scenarios are consistent with acute exacerbation of native-lung IPF and subradiographic pneumonitis of the allograft caused by CMV disease.
Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.
Clostridium difficile infection (CDI) is a major cause of morbidity and mortality especially in the healthcare setting. Fecal microbiota transplant (FMT) is an emerging treatment for CDI, namely for recurrent or refractory disease. A 57 year old Caucasian male with history of chronic idiopathic pulmonary fibrosis was transferred to our institution for lung transplant evaluation due to worsening oxygen requirement. His course was complicated by respiratory failure requiring mechanical intubation and later veno-venous extracorporeal membrane oxygenation. He required tracheostomy for prolonged mechanical ventilation dependence, and his transplant evaluation was expedited. Seventeen days into his course, he developed severe diarrhea with leukocytosis to 13.1. CDI was confirmed by stool PCR and oral vancomycin with intravenous metronidazole was initiated. Active listing for transplant was put on hold as a result. Our team was consulted for consideration of FMT given that his clinical status and requirement for lung transplant might not allow him to survive a full course of standard CDI therapy despite the fact he did not meet previously suggested criteria for FMT. The patient was subsequently rapidly prepped with 8L of polyethylene glycol solution via nasogastric tube, and CDI treatment was held the evening prior to the procedure. A bedside colonoscopy with FMT was performed in the ICU. Afterwards, the patient was given 4mg of loperamide, and all antibiotics were held. Twenty-four hours later, the patient's leukocytosis decreased to 8.3, and after consultation with the infectious disease service, he was reactivated on the lung transplant list. Six days later, the patient underwent successful double lung transplant. He was empirically treated with a fourteen day course of metronidazole following his operation. The patient continued to clinically improve, and one month after his CDI treatment with FMT, he was discharged to an acute rehabilitation facility. Nine months post-lung transplant, the patient remains free of CDI recurrence despite the need for antibiotics for a subsequent pneumonia and continued immunosuppressive agents. This case was the first at our institution where FMT was used outside of the previously established criteria and suggests a need to include the use of FMT in the critically ill patient in whom active CDI precludes their candidacy for a potentially life-saving intervention.
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Patients who need abdominal organ transplantation are at high risk for community-acquired, nosocomial, and opportunistic infections. In part, this is due to the invasive procedures they undergo, as well as the immunosuppression they require. This review highlights the infections that these vulnerable patients may develop. The current epidemiology, diagnosis, and management of common infections in liver, kidney, pancreas, and intestinal transplant (IT) recipients are summarized here.
Strongyloides stercoralis is an intestinal nematode endemic in the tropics and subtropics. Immunocompetent hosts typically are asymptomatic, despite chronic Strongyloides infection. In contrast, immunocompromised patients are at risk for hyperinfection syndrome and disseminated disease, with a fatality rate >50%. The infection source for immunocompromised patients, such as solid organ transplant recipients, is not always apparent and might result from reactivation of chronic infection after initiation of immunosuppressive therapy or transmission from the donor. In October 2012, the United Network for Organ Sharing (UNOS) notified CDC of a left kidney and pancreas recipient in Pennsylvania diagnosed with strongyloidiasis. This report summarizes the results of the investigation of the source of Strongyloides infection in three of four organ recipients. Testing of pretransplant donor and recipient sera confirmed that infection in the recipients was donor derived. This investigation underscores the importance of prompt communication between organ procurement organizations, transplant centers, and public health authorities to prevent adverse events in recipients when transmission is suspected. Additionally, it emphasizes the utility of stored pretransplant samples for investigation of suspected transplant-transmitted infections and the need to consider the risk for Strongyloides infection in organ donors.
Strongyloides is a parasite that is common in tropical regions. Infection in the immunocompetent host is usually associated with mild gastrointestinal symptoms. However, in immunosuppressed individuals it has been known to cause a “hyperinfection syndrome” with fatal complications. Reactivation of latent infection and rarely transmission from donor organs in transplanted patients have been suggested as possible causes. Our case highlights the importance suspecting Strongyloides in transplant recipients with atypical presentations and demonstrates an incidence of donor derived infection. We also review the challenges associated with making this diagnosis.
Patients undergoing thoracic organ transplantation procedures involving the heart or lung are at increased risk for developing a wide variety of infections due to their underlying immunosuppression and/or other factors. Lung transplant recipients are at high risk for developing infections caused by bacteria, viruses, and opportunistic fungi, whereas heart transplant recipients are at risk for developing infections caused by these same microorganisms, as well as parasitic infections, including toxoplasmosis and New World trypanosomiasis. This review will highlight the various infections that thoracic organ transplant recipients may develop following their procedures.