Search

Background Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. Methods This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12. Results Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48). Conclusions Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy.

Background Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. Objective The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. Methods This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. Results A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. Conclusion and Relevance This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Immunization rates in pre-liver transplant patients have been historically below rates for immunocompetent patients. At Cleveland Clinic, an infectious diseases (ID) consult is required for all patients during the liver transplant evaluation and may beneficially impact vaccination rates. The goal of this study was to evaluate pre-transplant vaccination rates in pre-liver transplant candidates. This single-center, retrospective chart review included adults transplanted between January 1, 2013, and December 31, 2016. Prior to transplant, rates of vaccination and/or documented seropositivity were 35% for hepatitis B vaccine, 92% for hepatitis A vaccine, 57% for pneumococcal conjugate vaccine, 62% for pneumococcal polysaccharide vaccine, and 77% for influenza vaccine. Vaccination rates were higher than to previously reported. Rates were also higher for several vaccines compared to transplant candidates for other organs without ID consult. With ongoing ID consult requirements for liver transplant candidates, combined with standardization of vaccine recommendations via technology, and increased multi-disciplinary collaboration, vaccination rates should improve further.

Objective: To review the use of rabbit antithymocyte globulin (rATG) induction therapy in liver transplant recipients. Data Sources: A MEDLINE literature search (inception to March 2016) was conducted using the search terms rabbit antithymocyte globulin, liver transplantation, and induction. References from extracted sources were further searched for any relevant, missed data sources. Study Selection and Data Extraction: All English-language randomized and observational studies were included. Data Synthesis: A total of 9 studies were included in this review evaluating rATG’s use for induction therapy. All studies were single-center analyses. rATG induction is utilized to delay calcineurin inhibitor initiation and to minimize or avoid steroids. Patients receiving rATG induction tended to have improved renal function compared with patients not receiving induction. Overall, rejection rates tended to be lower in recipients administered rATG. Regimens varied in each study, with most recipients receiving 2 to 3 doses of induction therapy. Conclusions: rATG induction therapy may lead to improved renal function and lower rejection rates following liver transplant. The use of this medication can help avoid unwanted adverse effects from other immunosuppression agents. Because of the potential benefits with this induction agent, rATG may have a larger role in induction therapy for liver transplant recipients.

tudy Objective It is unknown if β-lactam monotherapy is sufficient for complicated intra-abdominal infections or if broader coverage is required, such as with vancomycin. This study sought to determine the clinical outcomes of piperacillin/tazobactam (PIP/TAZ) monotherapy compared to combination therapy with vancomycin and PIP/TAZ for complicated intra-abdominal infections among patients within a surgical intensive care unit (ICU). Design Retrospective cohort study. Setting Three surgical ICUs at a tertiary academic medical center. Patients Four hundred seventeen patients with a secondary peritonitis identified by International Classification of Diseases, Ninth Revision codes who received either PIP/TAZ monotherapy (228 patients) or PIP/TAZ and vancomycin combination therapy (189 patients). Measurements and Main Results The primary outcome was day 28 clinical cure; secondary outcomes included day 7 clinical cure, length of stay (LOS), and mortality. There were no statistically significant differences between the monotherapy and combination therapy groups with respect to day 28 clinical cure (33.9% vs 25.5%, p=0.064), day 7 clinical cure (23.6% vs 17.6%, p=0.14), or 28-day mortality (7% vs 7.9%, p=0.72). LOS in the ICU was significantly shorter in the monotherapy group (6 days) compared with the combination therapy group (7 days; p=0.04); however, hospital LOS was not significantly different. Conclusions No difference was observed in clinical cure rates at day 28 or day 7 between those who received PIP/TAZ monotherapy compared to PIP/TAZ and vancomycin combination therapy.

Key Points 1. Our increasing understanding of signaling pathways and cellular interactions in transplant immunobiology and the availability of novel immunosuppressive agents have facilitated targeted strategies. 2. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances). 3. By regulatory mandate, the requirement for the primary endpoint to be a composite of death, graft loss, and rejection remains intact; however, current and future clinical trials could incorporate key secondary endpoints that address renal and metabolic derangements. Liver Transpl, 2011. © 2011 AASLD.

Background There is a growing need for robust antimicrobial stewardship interventions in both ambulatory and solid organ transplant (SOT) populations. Methods A retrospective quasi-experiment was conducted to evaluate the impact of a pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus (CMV) viremia in ambulatory SOT recipients. The intervention consisted of (a) real-time CMV DNA surveillance and result notification conducted by the pharmacist and (b) recommendations for the optimization of drug therapy provided at the time of result notification. The intervention period was compared to a pre-intervention period of usual care. Of 431 adult SOT recipients who had an initial quantifiable CMV viral load in the ambulatory setting, 185 received antiviral induction therapy and were included for analysis. Results Significantly fewer patients in the intervention period reached a CMV viral load >10 000 IU/mL immediately prior to treatment (10.6% vs 27.3%; P = 0.004), and a significantly greater proportion of patients in the intervention period achieved CMV eradication at 21 days (84.5% vs 71.7%; P = 0.038). Additional differences favoring the intervention period were antiviral initiation within 5 days of the first quantifiable CMV DNA (62.4% vs 55.0%; P = 0.02) and time-to-CMV eradication (25.5 vs 28.9 days; P = 0.003). Although not significant, there were also numerical reductions in CMV-related hospital admissions (11.9% vs 19.0%; P = 0.188) and CMV disease (5.9% vs 12.0%; P = 0.151) during the intervention period, as well as fewer episodes of CMV resistance at 1-year (2.3% vs 4.0%; P = 0.689). Conclusion Together, these findings suggest a potential role for pharmacist involvement in CMV surveillance and treatment optimization in ambulatory SOT recipients.

The Scientific Studies Committee of the Surgical Infection Society undertook the present study to examine the prevalence of and indications for antimicrobial use in intensive care units where members of the Society practice.Information and data collection sheets were posted on the Internet for download by members interested in participating. All centers were required to obtain approval from their local human subjects research office or equivalent. A one-week time was set during which the center could collect information on any one day, at the center's convenience. Data collection sheets were then sent to the lead author for analysis. Seventeen centers reported data for 371 patients in 22 intensive care units.Trauma and general surgical patients comprised 224 of the patients (60%). The indications for anti-infective agents were prophylactic (22%), empiric (27%), therapeutic with known pathogen (41%), therapeutic without known pathogen (e.g., cellulitis) (4%), insistence of influential practitioner (4%), or non-anti-infective purposes (e.g., erythromycin for gastric motility) (2%). Only 44%, 29%, and 54% of the orders for prophylactic, empiric, and therapeutic antibiotics, respectively, had date-certain stop dates. The antimicrobial drugs most commonly used were vancomycin, piperacillin-tazobactam, and fluconazole.Most patients were receiving antimicrobial agents. Polypharmacy was common. Most patients did not have a date-certain stop date. This study sets the benchmark for future study regarding antibiotic prescribing behavior in surgical intensive care units.