Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes.

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.

COVID-19 in organ donors: An organ procurement organization perspective.

BACKGROUND: The COVID-19 pandemic presented a significant challenge for Organ Procurement Organizations (OPOs) with the use of SARS-CoV-2 positive donors varying widely. This study used detailed single OPO data to determine the success of using SARS-CoV-2 positive donors. METHODS: We performed a retrospective cohort study including all SARS-CoV-2 positive donors referred to the Gift of Life OPO from January 1, 2021, to June 30, 2023. Descriptive analyses were performed to characterize referral and organ utilization. RESULTS: There were 861 organ referrals with 1 positive SARS-Cov-2 test: 282 were ruled out with telephone evaluation, 431 referrals were ruled out with onsite evaluation ("evaluated nondonors") and 148 became donors. For donors who had both nasopharyngeal and lower respiratory testing completed, there was notable result discordance observed. Median cycle threshold (Ct) values were similar between donors and evaluated nondonors with no change in median donor Ct values over the study period. Transplanted organs from COVID-positive donors included 27 hearts, 88 livers, 5 pancreata, and 107 kidneys; no lung donation occurred. The proportion of COVID-positive donors significantly increased over the study period. CONCLUSION: This large volume donor referral study demonstrates increasing COVID-19 referrals progressing to donation over time, supporting the increased use of these donors for nonlung transplantation.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Clinical Outcomes and Risk Factors for Carbapenem-resistant Enterobacterales Bloodstream Infection in Solid Organ Transplant Recipients.

BACKGROUND: The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. METHODS: A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. RESULTS: Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)' liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)' lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)' and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. CONCLUSIONS: CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

The Impact of Reported ß-Lactam Allergy on Clinical Outcomes and Antibiotic Use Among Solid Organ Transplant Recipients.

Background: Reported ß-lactam allergies (BLAs) are common and frequently inaccurate, but there are limited data on the clinical implications of BLA among solid organ transplant (SOT) recipients. We examined the impact of BLA on clinical outcomes and antibiotic use among SOT recipients. Methods: This retrospective cohort study included adult patients undergoing single-organ heart, kidney, liver, lung, or pancreas transplant at a United States academic medical center from 1 April 2017 to 31 December 2020. Demographic and clinical data were collected from the electronic health record. Multivariate median regression was performed to evaluate the association between BLA and days alive and out of the hospital in the first 180 days posttransplant (DAOH180). Multivariate logistic regression was performed to evaluate the association between BLA and antibiotic use. Results: Among 1700 SOT recipients, 285 (16.8%) had a BLA at the time of transplant. BLA was not associated with DAOH180 (adjusted median difference, -0.8 days [95% confidence interval {CI}, -2.7 to 1.2]; P = .43). Patients with BLA were more likely to receive intravenous vancomycin (adjusted odds ratio [aOR], 1.8 [95% CI, 1.3-2.6]; P < .001), clindamycin (aOR, 9.9 [95% CI, 5.1-18.9]; P < .001), aztreonam (aOR, 19.6 [95% CI, 5.9-64.4]; P < .001), fluoroquinolones (aOR, 3.8 [95% CI, 2.8-5.0]; P < .001), or aminoglycosides (aOR, 3.9 [95% CI, 2.5-6.2]; P < .001). Conclusions: BLA was associated with use of ß-lactam alternative antibiotics but not DAOH180 among SOT recipients.

Impact of deceased organ donor injection drug use on donor culture positivity and recipient outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

Prevalence of carbapenemase-producing organisms among hospitalized solid organ transplant recipients, five US hospitals, 2019-2020.

BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five US hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert Carba-R assay to identify carbapenemase genes (blaKPC , blaNDM , blaVIM , blaIMP , blaOXA-48 ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of blaIMP and blaOXA variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: four blaKPC , one blaNDM , and two blaOXA-23 . CPOs were detected in two (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs.

Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes.

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.

Antibiotic Utilization in Deceased Organ Donors.

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.

Clinical prediction tool for extended-spectrum beta-lactamase-producing enterobacterales as the etiology of a bloodstream infection in solid organ transplant recipients.

BACKGROUND: Multidrug-resistant Gram-negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (EB) bloodstream infection (BSI). METHODS: A multicenter case-control study was performed. The source population included SOT recipients with an EB BSI between 2005 and 2018. Cases were those with ESBL-EB BSI; controls were those with non-ESBL EB BSI. The population was subdivided into derivation and validation cohorts based on study site. The predictive tool was developed in the derivation cohort through iterative multivariable logistic regression analyses that maximized the area under the receiver-operating curve (AUC). External validity was assessed using the validation cohort. RESULTS: A total of 897 SOT recipients with an EB BSI were included, of which 539 were assigned to the derivation cohort (135, 25% ESBL-EB) and 358 to the validation cohort (221, 62% ESBL-EB). Using multivariable analyses, the most parsimonious model that was predictive of ESBL-EB BSI consisted of 10 variables, which fell into four clinical categories: prior colonization or infection with EB organisms, recent antimicrobial exposures, severity of preceding illness, and immunosuppressive regimen. This model achieved an AUC of 0.81 in the derivation cohort and 0.68 in the validation cohort. CONCLUSIONS: Though further refinements are needed in additional populations, this tool shows promise for guiding empiric therapy for SOT recipients with EB BSI.

Risk Factors for Extended-Spectrum ß-lactamase-Producing Enterobacterales Bloodstream Infection Among Solid-Organ Transplant Recipients.

BACKGROUND: Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum ß-lactamase (ESBL)-producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs. METHODS: A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non-ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI. RESULTS: There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23-50.33; P < .001), a corticosteroid-containing immunosuppression regimen (aOR 1.30; 95% CI 1.03-1.65; P = .030), acute rejection treated with corticosteroids (aOR 1.18; 95% CI 1.16-1.19; P < .001), and exposure to third-generation cephalosporins (aOR 1.95; 95% CI 1.48-2.57; P < .001), echinocandins (aOR 1.61; 95% CI 1.08-2.40; P = .020), and trimethoprim-sulfamethoxazole (aOR 1.35; 95% CI 1.10-1.64; P = .003). CONCLUSIONS: We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed.

Impact of deceased donor multidrug-resistant bacterial organisms on organ utilization.

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.

Changes in Infective Endocarditis Admissions in Pennsylvania During the Opioid Epidemic.

BACKGROUND: With the current opioid crisis in the United States, infectious complications related to injection drug use are increasingly reported. Pennsylvania is at the epicenter of the opioid crisis, with the third highest rate of drug overdose deaths in the United States. METHODS: A retrospective cohort study was performed using the Pennsylvania Health Care Cost Containment Council database of all residents hospitalized for infective endocarditis (IE) in an acute care hospital from 1 January 2013 through 31 March 2017. Patients were separated into those with and those without substance use via diagnosis codes. The primary outcome was length of stay. Secondarily, we evaluated demographics, infection history, hospital charges, and insurance status. RESULTS: Of the 17 224 hospitalizations, 1921 (11.1%) were in patients with drug use-associated IE (DU-IE). Total quarterly IE admissions increased 20%, with a 6.5% increase in non-drug use-associated IE (non-DU-IE) admissions and a 238% increase in DU-IE admissions. In adjusted models, DU-IE was not associated with significant changes in length of stay (incidence rate ratio, 1.02; 95% confidence interval, .975-1.072; P = .36). Patients with DU-IE were predominantly insured by Medicaid (68.3% vs 13.4% for non-DU-IE), they had higher hospital charges ($86 622 vs $66 802), and they were more likely to leave against medical advice (15.7% vs 1.1%) (all P < .001). CONCLUSIONS: Our study demonstrates an increase in IE admissions, driven by an increase in admissions for DU-IE. The higher charges, proportion of patients on Medicaid, and rates of leaving against medical advice among the DU-IE group shows the downstream effects of the opioid crisis.

Early clinical experience of bacteriophage therapy in 3 lung transplant recipients.

Bacteriophage therapy (BT) uses bacteriophages to treat pathogenic bacteria and is an emerging strategy against multidrug-resistant (MDR) infections. Experience in solid organ transplant is limited. We describe BT in 3 lung transplant recipients (LTR) with life-threatening MDR infections caused by Pseudomonas aeruginosa (n = 2) and Burkholderia dolosa (n = 1). For each patient, lytic bacteriophages were selected against their bacterial isolates. BT was administered for variable durations under emergency Investigational New Drug applications and with patient informed consent. Safety was assessed using clinical/laboratory parameters and observed clinical improvements described, as appropriate. All patients received concurrent antibiotics. Two ventilator-dependent LTR with large airway complications and refractory MDR P. aeruginosa pneumonia received BT. Both responded clinically and were discharged from the hospital off ventilator support. A third patient had recurrent B. dolosa infection following transplant. Following BT initiation, consolidative opacities improved and ventilator weaning was begun. However, infection relapsed on BT and the patient died. No BT-related adverse events were identified in the 3 cases. BT was well tolerated and associated with clinical improvement in LTRs with MDR bacterial infection not responsive to antibiotics alone. BT may be a viable adjunct to antibiotics for patients with MDR infections.

Risk factors for multidrug-resistant organisms among deceased organ donors.

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.

A Clinical Prediction Tool for Extended-Spectrum Cephalosporin Resistance in Community-Onset Enterobacterales Urinary Tract Infection.

BACKGROUND: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB). METHODS: A case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping. RESULTS: A total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit P value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71. CONCLUSIONS: Community-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions.