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Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Background Emergency medicine (EM) pharmacists may be uniquely positioned to optimize discharge prescriptions for emergency department (ED) patients but the clinical significance of interventions and association with patient outcomes are not well-described. Objective To evaluate the clinical significance of EM pharmacist interventions completed during review of ED discharge prescriptions. Setting This study was conducted in an academic medical center ED. Methods: This was a retrospective observational study of patients discharged with prescriptions from the ED over two months. EM pharmacists reviewed discharge prescriptions and provided drug therapy recommendations. Two independent reviewers rated the clinical significance of interventions. High risk criteria were proposed a priori and included in a multivariable logistic regression analysis to identify variables independently associated with pharmacist intervention. Main Outcome Measure The primary outcome measure was the rate, type, and clinical significance of interventions associated with EM pharmacist review of discharge prescriptions. Results A total of 3107 prescriptions for 1648 patients were reviewed. Interventions occurred for 7.3% of patients with 29% of interventions rated as significant. The intervention rate was higher in patients with at least 1 high risk criteria versus those without (9.6% vs. 3.7%, p

Background Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil (MMF) and proton pump inhibitors (PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF-PPI versus patients taking MMF-ranitidine. Objective The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2RA). Methods This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation. Results Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2RA. There was no significant difference in acute rejection within 1 year (H2RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression (MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups. Conclusion Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2RA were not at increased risk of acute rejection within 1 year posttransplantation.

The goal of testosterone replacement therapy (TRT) is to return serum testosterone levels to within physiologic range and improve symptoms in hypogonadal men. Some of the symptoms aimed to improve upon include decreased libido, erectile dysfunction, infertility, hot flashes, depressed mood, and loss of muscle mass or hair. Clinical use of testosterone for replacement therapy began approximately 70 years ago. Over the decades, numerous preparations and formulations have been developed primarily focusing on different routes of delivery and thus pharmacokinetics (PKs). Currently the routes of delivery approved for use by the United States Food and Drug Administration encompasses buccal, nasal, subdermal, transdermal, and intramuscular (IM). Many factors must be considered when a clinician is choosing the most correct formulation for a patient. As this decision depends highly on the patient, active patient participation is important for effective selection. The aim of this review is to describe and compare all testosterone preparations currently available and approved by the United States Food and Drug Administration. Areas of focus will include pharmacology, PKs, adverse effects, and specifics related to individual delivery routes.

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.

Background Cytomegalovirus (CMV) infection causes significant morbidity and mortality in transplant recipients. Ganciclovir and valganciclovir have proven efficacy but are limited by resistance and toxicity, whereas foscarnet typically retains activity when CMV has become resistant to other antivirals. Foscarnet dosing used in practice may be discordant with what is recommended in product labeling, as the result of an unconventional dosing nomogram or prescriber preference; however, it is unknown how discordant foscarnet dosing affects outcomes. Objective Our purpose was to characterize the relationship between initial foscarnet dosing intensity (relative to product labeling) and key effectiveness and safety endpoints. Study design This single-center, retrospective study included immunosuppressed adults with CMV viremia who received foscarnet between January 2012–July 2017. Subjects were divided into low dose (LD) and non-low dose (NLD) groups, according to foscarnet dose intensity. The primary endpoint was time-to-CMV eradication. Secondary endpoints included time-to-CMV clearance, acute kidney injury, hematologic toxicity, and mortality. Results Of 87 subjects, 38 met inclusion. Primary immunosuppression reasons were solid organ (63%) or hematopoietic cell transplant (29%). Seventeen and 21 subjects were in the LD and NLD groups, respectively. Median time-to-CMV eradication was 17 days (LD group) versus 13 days (NLD group), p = 0.823. Median time-to-CMV clearance was also non-significant (p = 0.505). There was no association between initial foscarnet dosing intensity and acute kidney injury, hematologic toxicity, or mortality (24% in both groups). Conclusions These findings suggest outcomes may be sensitive to other factors and underscore the need for further studies to improve understanding of foscarnet dosing in immunosuppressed patients.

Objective Urinary tract infections (UTIs) are the most commonly occurring infectious complication following kidney transplantation. Questions remain regarding whether asymptomatic bacteriuria (ASB) should be treated. The aim was to evaluate the incidence and management of ASB in kidney transplant recipients at a large academic medical center. Methods All subjects receiving an isolated kidney transplant between September 2012 and October 2016, and with at least one ASB episode were included. Demographics, symptomatology, and urine culture data were collected on subjects with bacteriuria in the first year post-transplant. Cultures were classified by symptoms, ASB treatment trends were analyzed, and ASB-to-UTI progression was compared between ASB treatment and non-treatment. Results A total of 527 subjects were transplanted with 64 developing at least one ASB episode. The incidence of ASB was 12.1% and treated 74.6% of the time. Neither lack of ASB treatment (P = 0.463) nor ASB within the first month post-transplant (P = 0.303) were associated with ASB-to-UTI progression. Conclusion Despite high ASB treatment rate, this was not found to be protective against ASB-to-UTI progression. ASB within the first month post-transplant also did not correlate with increased progression risk. These results suggest minimization of ASB treatment in kidney transplant recipients remains an important antimicrobial stewardship target.

Background Vaccines prevent infections and avoid related complications. Low rates in immunocompromised patients are concerning due to increased morbidity. Vaccinations are less effective when administered post-transplant and should be administered prior. We describe pre-transplant vaccination rates among kidney or kidney-pancreas transplant recipients. Methods Retrospective review including adults receiving kidney or kidney-pancreas allografts at Cleveland Clinic from October 2013 to October 2016. Pre-transplant vaccinations, serologies, and transplant data were collected. Results 393 patients were included; median age was 53 years with most (46%) being Caucasian males. Influenza vaccination rate was 48%; receipt of at least one pneumococcal vaccine was 77%. Vaccination rates were higher among dialysis patients for pneumococcal, hepatitis B, and varicella vaccines; rates were also higher with infectious diseases consults. Conclusions Vaccination rates at our institution for kidney or kidney-pancreas transplant candidates are consistent with previous literature. Rates were higher for candidates with infectious diseases consults or receiving dialysis.

BACKGROUND Fusarium spp. infections have become an emerging and lethal threat to the immunocompromised patient population, especially those with neutropenia. Recently there have been increased reports in solid organ transplant recipients. Presentation is commonly as soft tissue infections several months post-transplant. With high morbidity and mortality, efficacious antifungal therapy is essential. This remains challenging with limited data and no established clinical breakpoints defined. CASE REPORT We report on a modified multi-visceral transplant patient that developed a Fusarium infection only 7 weeks post-transplant in the native hard palate and esophagus, without any soft tissue lesions, which persisted despite aggressive combination treatment with amphotericin B lipid complex and voriconazole. CONCLUSIONS Fusarium spp. infection in solid organ transplant is a significant challenge without clear diagnostic clinical indicators of infection, or specific time of onset, in addition to possible emergence of a more aggressive drug-resistant strain.

Background UTIs are the most common infection after renal transplant (RTx) with an incidence of 6–86%. Post-RTx UTI has been associated with risk for graft loss and mortality, and RTx recipients are at risk for multidrug-resistant (MDR) UTI given immunosuppression (IS) and instrumentation. We sought to evaluate the incidence, timing, microbiology, and MDR risk of post-RTx UTI, as well as to characterize asymptomatic bacteriuria (ASB) practices at our center. Methods This was a retrospective cohort of subjects with ≥1 positive culture (≥105 CFU/mL) during the first year post-RTx that were transplanted from September 1, 2012 to October 1, 2016. Each bacteriuria episode was adjudicated as cystitis, pyelonephritis, or ASB (Figure 1). Subjects without bacteriuria were excluded from primary analysis but used to calculate UTI incidence. The primary outcome was 1-year symptomatic UTI incidence. Secondary outcomes: incidence of cystitis, pyelonephritis, and ASB; time-to-first UTI; microbiologic trends; and presence of MDR risk factors. Results Baseline characteristics: 52% male, median age 57 years, 65% stented, 34% antithymocyte globulin induction, 94% standard IS regimen (tacrolimus/mycophenolate/prednisone), 93% trimethoprim/sulfamethoxazole prophylaxis, and 21% receipt of IV antibiotics for ≥48 hours within 90 days of first positive culture (IV Abx); Of 527 RTx subjects, 100 had ≥1 positive culture. The 100 subjects had 234 cultures representing 359 isolates. Primary outcome: 12.1% symptomatic UTI incidence. Secondary outcomes (1-year incidences): 18.6% positive culture, 4.3% cystitis, 8.6% pyelonephritis, 11.9% ASB. Time to the first symptomatic UTI was a median of 50 days. A summary of microbiologic results can be found in Figure 2. ASB occurred 130 times and was treated 74.6% of the time (Figure 3). Significant risk factors for MDR UTI included female gender (P = 0.005), IV abx (P = 0.001), and recurrent UTI (P = 0.017). Conclusion Incidence of symptomatic UTI at our center was lower than previous reports. E. coli and E. faecalis were the most common urinary pathogens identified. MDR risk factors identified were biologically plausible and consistent with prior literature. ASB treatment occurred frequently and is an area to target stewardship interventions. Disclosures All authors: No reported disclosures.

Stiction in control valves is one of the long-standing problems in the process industries which lead to oscillations in closed loop systems. Numerous methods have been developed to detect stiction in linear closed-loop systems. Almost all of these methods utilize the fact that the presence of stiction in control valves introduces nonlinearities in the closed loop control system. However, there exists no measure of reliability for the results provided by these techniques. In this work, using frequency domain analysis of closed loop systems, a measure of reliability is developed for model based stiction detection approaches.

Background Adherence rates for recommended pre-transplant (pre-txp) vaccinations in pediatric solid-organ transplant (SOT) patients are variable and practice-dependent. Cleveland Clinic Children’s Hospital (CCCH) pre-txp adherence rates for select vaccines have not been described. The purpose of this study was to evaluate pre-txp adherence rates for the following vaccines: hepatitis B, influenza, pneumococcal conjugate (PCV13), pneumococcal polysaccharide (PPSV23), and hepatitis A (if at-risk). Methods This retrospective cohort study included patients undergoing initial pediatric heart, kidney, liver, or intestine/multi-visceral transplant at CCCH between 1/1/14 and 7/31/17. Data collected from the electronic medical record and Ohio Department of Health Statewide Immunization Information System included demographics, transplant-related data, immunization administration history, and quantitative/qualitative values for titer/serology. The primary objective of vaccination adherence rate was defined as the aggregate of patients who had completed the vaccine series, had positive titer/serology data, or were ineligible to receive the vaccine due to age or administration restrictions. Data are descriptive in nature and reported as number (percent) or median (interquartile range), as appropriate. Results 64 pediatric SOT recipients met inclusion criteria. Median age was 7.9 (2.1, 15.8) years. Majority of patients were American (73%) and male (63%). Most common organ was heart (41%), followed by liver (25%), kidney (21%), and intestine/multi-visceral (13%). Sixty-three (98%) patients underwent ID pre-txp evaluation. CCCH adherence rates were highest for hepatitis B at 92%, followed by PCV13 and PPSV23 at 84%, and influenza at 72%. Thirty-two (50%) patients were indicated to receive the hepatitis A vaccine and the respective adherence rate was 91%. Vaccination adherence by SOT team is described in Figure 1. Conclusion CCCH pre-txp vaccination adherence rates are higher than previously reported. Opportunities for improvement include influenza vaccination adherence across all SOT teams and PCV13/PPSV23 vaccination adherence in intestine/multi-visceral transplant patients. Figure 1: CCCH SOT team vaccination adherence rates. Disclosures All authors: No reported disclosures.

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.

Background Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. Methods This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (±60 days). Results The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR = 1.25, 95% CI = 1.00-1.56, P = .048) and antibiotic exposure for urinary tract infections (UTI) (AOR = 4.17, 95% CI = 1.12-15.54, P = .034). Proton pump inhibitor use was not associated with CDI (OR = 0.81, 95% CI = 0.29-2.29, P = .691). Conclusion Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population.

Background There is a demand for stewardship implementation and research in ambulatory and SOT populations. Few studies focus on outpatient stewardship interventions, and none has focused on timely recognition of CMV in outpatient SOT recipients. This study sought to determine the effect of real-time CMV result notification paired with pharmacist intervention on virologic and clinical outcomes in outpatient SOT recipients. Methods Quasi-experimental study comprised of two 6-month phases. In the pre-intervention phase, pharmacists were not involved in management of outpatient CMV viremia. In the intervention phase, pharmacists received real-time email notification of positive blood CMV results for review and intervention as necessary. The primary endpoint was rate of viremia eradication at 21 days from therapy initiation. Secondary endpoints: time to antiviral initiation and viremia eradication, rate of CMV invasive disease and hospital admission, and adverse drug events. Results 88 of 213 screened patients were included in the primary analysis (n = 49 and 39 in the pre-intervention and intervention groups, respectively). Baseline characteristics were similar, including transplant type (34% vs. 41% liver, 24% vs. 28% kidney, 14% vs. 17% lung, 14% vs. 10% heart), CMV serostatus (53% vs. 64% D+/R-), and maintenance immunosuppression. A total of 73 recommendations were made with 89% acceptance. Baseline CMV viral load >10,000 IU/mL occurred in 12 (24%) vs. 6 (15%) patients (P = 0.29). Of treated patients, 42 (85%) vs. 32 (82%) achieved CMV eradication at 21 days (P = 0.64), 10 (20%) vs. 5 (12%) required admission for CMV management (P = 0.35), 7 (14%) vs. 3 (7%) developed CMV invasive disease (P = 0.50), and 29 (60%) vs. 25 (66%) received antiviral within 5 days (P = 0.61). There were no statistically significant differences in time to antiviral initiation (45 vs. 41 hours; P = 0.64) or viremia eradication (19 vs. 18 days; P = 0.44). Conclusion CMV eradication at 21 days was not significantly different between groups; however, fewer patients in the intervention experienced elevated baseline viral load, CMV invasive disease, and hospital admission. These secondary endpoints suggest possible benefit from the intervention and warrant further characterization and study. Disclosures All authors: No reported disclosures.