Risk factors and outcomes of bloodstream infection from a urinary source in kidney transplant recipients.

BACKGROUND: Bacteriuria is common among kidney transplant recipients (KTR). Risk factors and outcomes associated with bloodstream infection due to a urinary source (BSIU) in KTR are poorly understood. METHODS: This single center case-control study from 2010 to 2022 compared KTR with BSIU to those with bacteria without bloodstream infection (BU). Multivariable logistic regression identified BSIU risk factors, and Cox models assessed its impact on graft failure. RESULTS: Among 3435 patients, who underwent kidney transplantation at Emory Hospital, 757 (22%) developed bacteriuria, among whom 142 (18.8%) were BSIU. Male sex, presence of Escherichia coli, Klebsiella pneumoniae, or Pseudomonas species in urine culture, urethral stricture, neuromuscular bladder disorder, and history of diabetes-induced renal failure were independently associated with increased odds of BSIU (Male sex: aOR 2.29, 95% CI 1.52, 3.47, E. coli: aOR 5.14, 95% CI 3.02, 9.13; K. pneumoniae aOR 3.19, 95% CI 1.65, 6.27, Pseudomonas spp aOR 3.06, 95% CI 1.25, 7.18; urethral stricture: 4.10, 95% CI 1.63, 10.3, neuromuscular bladder disorder aOR 1.98, 95% CI 1.09, 3.53, diabetes: aOR 1.64, 95% CI 1.08, 2.49). BSIU was associated with increased hazard of graft failure (HR 1.52, 95% CI 1.05, 2.20). CONCLUSION: Close monitoring is warranted for male KTR with bacteriuria, those with urine cultures positive for Pseudomonas spp, K. pneumoniae, or E. coli, as well as KTR with a history of diabetes-induced renal failure, urethral stricture, or neuromuscular bladder disorder due to their risk for developing BSIU. Future research should explore strategies to mitigate BSIU risk in these high-risk KTR and reduce the associated risk of long-term graft failure.

The Burden and Impact of Early Post-transplant Multidrug-Resistant Organism Detection Among Renal Transplant Recipients, 2005-2021.

Background: Reducing the burden of multidrug-resistant organism (MDRO) colonization and infection among renal transplant recipients (RTRs) may improve patient outcomes. We aimed to assess whether the detection of an MDRO or a comparable antibiotic-susceptible organism (CSO) during the early post-transplant (EPT) period was associated with graft loss and mortality among RTRs. Methods: We conducted a retrospective cohort study of RTRs transplanted between 2005 and 2021. EPT positivity was defined as a positive bacterial culture within 30 days of transplant. The incidence and prevalence of EPT MDRO detection were calculated. The primary outcome was a composite of 1-year allograft loss or mortality following transplant. Multivariable Cox hazard regression, competing risk, propensity score-weighted sensitivity, and subgroup analyses were performed. Results: Among 3507 RTRs, the prevalence of EPT MDRO detection was 1.3% (95% CI, 0.91%-1.69%) with an incidence rate per 1000 EPT-days at risk of 0.42 (95% CI, 0.31-0.57). Among RTRs who met survival analysis inclusion criteria (n = 3432), 91% (3138/3432) had no positive EPT cultures and were designated as negative controls, 8% (263/3432) had a CSO detected, and 1% (31/3432) had an MDRO detected in the EPT period. EPT MDRO detection was associated with the composite outcome (adjusted hazard ratio [aHR], 3.29; 95% CI, 1.21-8.92) and death-censored allograft loss (cause-specific aHR, 7.15; 95% CI, 0.92-55.5; subdistribution aHR, 7.15; 95% CI, 0.95-53.7). A similar trend was seen in the subgroup and sensitivity analyses. Conclusions: MDRO detection during the EPT period was associated with allograft loss, suggesting the need for increased strategies to optimize prevention of MDRO colonization and infection.

Advancing cytomegalovirus prevention in solid organ transplant recipients: The promise of cell-mediated immune assays.

Cytomegalovirus (CMV) infections are a major source of morbidity and mortality in solid organ transplant recipients. Prophylactic, preemptive, and hybrid prevention strategies have traditionally been the mainstay of CMV prevention but there is growing interest in the use of CMV cell-mediated immune assays to inform novel approaches to risk stratification. Recent evidence suggests that CMV interferon-gamma release assays can offer predictive insights into the risk for CMV-related illnesses, raising the potential for tailored CMV prevention strategies anchored to each individual's unique CMV immune profile. However, the predictive capacity of these assays for CMV-related illnesses can be profoundly influenced by when they are performed relative to transplant, and the induction immunosuppressive regimen the patient has received. In this review, we explore the relevant literature shaping our understanding of the optimal use of these assays. Furthermore, we also highlight the benefits of quantifying the CD4+ and CD8+ T-Cell responses to CMV, which is offered by some interferon-gamma release assays utilizing intracellular cytokine staining, for providing a holistic assessment of the recovery of cell-mediated immunity post-induction immunosuppression.

Heart of the matter-infection and xenotransplantation.

In this clinicopathological conference, invited experts discussed a previously published case of a patient with nonischemic cardiomyopathy who underwent heart transplantation from a genetically modified pig source animal. His complex course included detection of porcine cytomegalovirus by plasma microbial cell-free DNA and eventual xenograft failure. The objectives of the session included discussion of selection of immunosuppressive regimens and prophylactic antimicrobials for human xenograft recipients, description of infectious disease risk assessment and mitigation in potential xenograft donors and understanding of screening and therapeutic strategies for potential xenograft-related infections.

Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia. METHODS: We conducted a single-center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R-: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration. RESULTS: Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55-2.46) and an average of 24 (95% CI: 16.40-31.98) additional days of DNAemia. There was no difference in CMV end-organ disease or 1-year all-cause mortality between moderate-risk RTRs. CONCLUSIONS: The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs. KEY SUMMARY: The use of ultrasensitive CMV qNAT assays in moderate-risk CMV renal transplant recipients is associated with earlier detection and longer durations of CMV DNAemia without impacting CMV end-organ disease or 1-year mortality.

Long-term Dalbavancin for Suppression of Gram-Positive Chronic Left Ventricular Assist Device Infections.

Background: Infection is the leading cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). Prolonged suppressive therapy should be strongly considered and is often used in patients with recurrent infections when source control cannot be achieved. Dalbavancin is a promising option in patients with LVADs requiring prolonged durations of antibiotic therapy, especially when no oral alternatives are available. Methods: This case series included 8 patients receiving dalbavancin for the long-term suppression of gram-positive infections at Emory University Hospital and Emory St Joseph's Hospital. Results: The overall incidence of breakthrough infections occurred in 5 of the 8 patients included in the study. One patient experienced an early breakthrough infection within 1 month of dalbavancin initiation. Another experienced a breakthrough infection within 3 and 6 months of dalbavancin initiation, and the final 3 patients experienced a breakthrough infection within 6 and 12 months. The average duration of dalbavancin suppression therapy among all patients was 229 days, and no adverse effects were reported. Conclusions: Dalbavancin is a promising option in patients who require long-term suppression for chronic gram-positive LVAD infections, given its unique pharmacokinetic profile and excellent tissue penetration. The use of biweekly dalbavancin infusions in our 8 patients prevented infection for an extended period of time despite some of the patients not being able to consistently receive infusions. Larger studies are needed to determine the efficacy and safety of using dalbavancin for long-term suppression of gram-positive LVAD infections.

Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.

Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum ß-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.

Management and outcomes of heart transplant candidates with bloodstream infection on temporary mechanical circulatory support.

The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between January 1, 2013, and April 30, 2023, N = 136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) patients were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (interquartile range 28.3). All TMCS-I were reactivated for transplant within 48 to 72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (p = 0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment.

Complex considerations - Fever and pancytopenia after solid organ transplantation.

This case describes a 42-year-old man who underwent kidney transplantation and developed fevers, pancytopenia, and elevated liver function tests starting on post-operative day 9. An extensive microbiologic and molecular workup was performed, ultimately leading to a diagnosis of donor-derived toxoplasmosis with associated hemophagocytic lymphohistiocytosis in the recipient. This case highlights the potential for post-transplant toxoplasmosis in high-risk mismatch (D+/R-) recipients, as well as the role of Toxoplasma-targeted prophylaxis in such patients.

Candidemia in thoracic solid organ transplant recipients: Characteristics and outcomes relative to matched uninfected and bacteremic thoracic organ transplant recipients.

BACKGROUND: Little is understood about the risk factors and outcomes from candidemia in thoracic solid organ transplant recipients. METHODS: This is a single-center retrospective cohort study of patients undergoing heart or lung transplant between January 1, 2013 and December 31, 2022. We performed two comparisons among heart and lung transplant recipients: (1) recipients with candidemia versus matched, uninfected recipients, and (2) recipients with candidemia versus recipients with bacteremia. RESULTS: During the study 384 heart and 194 lung transplants were performed. Twenty-one (5.5%) heart and six (3.1%) lung recipients developed candidemia. Heart recipients with candidemia were more likely to have had delayed chest closure (38.1% vs. 0%, p < .0001), temporary mechanical circulatory support (57.1% vs. 11.9%, p = .0003), and repeat surgical chest exploration 76.2% vs. 16.7%, p < .0001) than uninfected controls. Heart and lung recipients who developed candidemia were more likely to have been on renal replacement therapy prior to infection relative to uninfected controls (57.1% vs. 11.9%, p = .0003 and 66.7% vs. 0%, p = .0041, respectively). Heart recipients with candidemia had significantly lower post-transplant survival and lower post-infection survival relative to matched uninfected controls and heart recipients with bacteremia, respectively (p < .0001 and p = .0002, respectively). CONCLUSIONS: Candidemia following heart and lung transplantation is associated with significant morbidity and mortality. Further research is needed to understand if heart recipients with delayed chest closure, temporary mechanical circulatory support, renal replacement therapy, and repeat surgical chest exploration may benefit from targeted antifungal prophylaxis.

Utility of deceased donor cultures in solid organ transplantation in preventing donor-derived bacterial and fungal infectious diseases transmission.

Deceased donor and organ perfusion fluid cultures are obtained in order to inform recipient antimicrobial management and therefore reduce the risk of donor-derived bacterial and fungal infections. However, important heterogeneity exists in laboratory practice across organ procurement organizations and clinical management of culture results across transplant centers. While not standardized, the clinical approach to donors with positive bacterial and/or fungal cultures should be informed by the risk of donor-derived infection (DDI) and the consequence of organ non-utilization and account for potential unintended effects of antimicrobial use in the recipient. In this review, we summarize the literature on bacterial and fungal DDIs, describe the significance of positive cultures by anatomic site, and summarize current guidance on the management of positive cultures from donors or preservation fluids.

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.

Lung abscess and empyema in a heart transplant recipient from Thailand.

The case discussed involves a 69-year-old Thai woman who underwent orthotopic heart transplantation 9 months before this event. She presented with fever without localizing signs or symptoms. However, her chest images revealed mass-like consolidation in the left upper lobe. Blood culture and lung tissue identified Rhodococcus equi. She was successfully treated with a combination of antimicrobial therapy, optimization of immunosuppressants, and surgical resection.

Mitigation strategies among cutaneous T-cell lymphoma patients with positive Staphylococcus aureus skin and soft tissue cultures have unclear impacts on the risk of subsequent bacteremia.

Infections originating in the skin/soft tissue are a major cause of mortality in cutaneous T-cell lymphoma (CTCL). We performed a retrospective analysis to characterize cutaneous cultures and assess risk factors for bacteremia among 69 patients with CTCL. Cutaneous infections and antimicrobial resistance were common. Black race and lymph node involvement were associated with bacteremia. Mitigating strategies for invasive infections in CTCL remain unclear. HighlightsSkin/soft tissue infections are common in cutaneous T-cell lymphoma (CTCL).Black race, lymph node involvement, and positive cultures for S. aureus, Gram-negative bacteria, or multiple organisms were associated with an increased rate of bacteremia.The role of antimicrobial prophylaxis and staphylococcus decolonization is unclear.

Deceased donors with multidrug-resistant organisms: implications and future directions.

PURPOSE OF REVIEW: Organ utilization from donors infected or colonized with multidrug-resistant organisms (MDROs) remains inconsistent, and hesitancy to accept organs from these donors may relate to poor outcomes among solid organ transplant recipients with MDRO donor-derived infections (DDIs). An improved understanding of the risk factors for donor MDRO colonization or infection and the risk of MDRO DDI is needed to safely expand the donor pool while minimizing unnecessary organ discard. RECENT FINDINGS: Recent studies have begun to delineate risk factors for MDRO acquisition among deceased donors and the epidemiology of MDRO DDIs, but additional efforts are warranted to inform optimal approaches to donor evaluation, risk stratification, management, interfacility and interagency data sharing, and approaches to recipient management. SUMMARY: This review summaries recent data regarding risk factors for MDRO colonization and infection in deceased donors, epidemiology of MDRO DDIs, and current approaches to donors harboring MDROs and provides a framework for future research and collaboration.

A new chapter in an evolving pandemic: Successful pediatric liver transplantation with SARS-CoV-2+ donors.

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors. METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform. RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a 16-month-old boy with cardiopulmonary arrest of unknown etiology. Three NAT tests (2 NP swab/1 BAL) prior to procurement failed to detect SARS-CoV-2. The diagnosis was made when the medical examiner repeated 2 NP swab NATs and an archive plasma NAT, all positive for SARS-CoV-2. Both 2-year-old recipients continue to do well 8 months post-transplant, with excellent graft function and no evidence of SARS-CoV-2 transmission. CONCLUSIONS: This is the first report to describe successful pediatric liver transplantation from SARS-CoV-2+ donors. These data reinforce the adult transplant experience and support the judicious use of SARS-CoV-2+ donors for liver transplantation in children. With SARS-CoV-2 becoming endemic, the concern for donor-derived viral transmission must now be weighed against the realized benefit of life-saving transplantation in the pediatric population as we continue to work toward donor pool maximization.

A Case of "Cryptammonia": Disseminated Cryptococcal Infection Generating Profound Hyperammonemia in a Liver Transplant Recipient.

Mycoplasma and Ureaplasma infections have been described as a cause of hyperammonemia syndrome leading to devastating neurological injury in the post-transplant period, most commonly in lung transplant recipients. The occurrence of significant hyperammonemia caused by other urease-producing organisms remains unclear. We describe a case of disseminated cryptococcosis presenting with profound hyperammonemia in a 55-year-old orthotopic liver transplant recipient. Through a process of elimination, other potential causes for hyperammonemia were excluded revealing a probable association between hyperammonemia and disseminated cryptococcosis.