PGY1 Pharmacy Residency

Time to therapeutic tacrolimus levels and association with acute cellular rejection and de novo donor-specific antibody development in lung transplant recipients

Corey Dinunno, PharmD; Christine Pham, PharmD; Brett Pierce, PharmD; Ahmad Goodarzi, MD; Simon W. Yau, MD; Jihad G. Youssef, MD; Duc T. Nguyen, MD, PhD; Edward A. Graviss, PhD, MPH; Howard J. Huang, MD

PURPOSE Tacrolimus (FK506) is standard of care for preventing rejection in lung transplant for maintenance immunosuppression. Both acute cellular rejection (ACR) and de novo donor-specific antibodies (dnDSAs) are strongly associated with development of chronic lung allograft dysfunction. The optimal time to therapeutic (TTT) FK506 level post-transplant has not been established, and a standardized dosing strategy for all patients in the immediate post-transplant period may be inappropriate. We evaluated whether TTT FK506 impacted ACR and dnDSA rates within 6 months of lung transplantation.

METHODS

We retrospectively reviewed lung transplant recipients between 5/2016 – 12/2019. We excluded patients who did not receive FK506, received their first dose >48 hours post-transplant, were transitioned off FK506 during the study period, or expired within 30 days. Our primary outcome was a composite of ACR and dnDSA development within 6 months for patients achieving therapeutic FK506 (8-15 ng/mL) within 7 days, versus >7 days. Secondary endpoints included: time within therapeutic range (TTR) at 1 month and incidence of acute kidney injury (AKI) within 14 days.

RESULTS Median TTT was 7 days (IQR 5.0-10.0) in 222 patients. There was no difference in ACR [7.6% vs 9.7% (p=0.63)] or dnDSA [35% vs 44% (p=0.20)] between patients achieving therapeutic FK506 <7 days vs >7 days. Recipients therapeutic <7 days had a longer median time to dnDSA development (44 days vs 27 days, p=0.043). TTR at 1 month was longer in patients therapeutic <7 days (40% vs 28%, p<0.001). Neither median nor percentage of TTR had an impact on the composite outcome (HR 0.99; 95% CI 0.95-1.03). AKI incidence (>stage 2) was similar (40.3% vs 38.8%, p=0.82) between groups. Multivariate analysis identified receipt of a double lung transplant as the only covariate associated with a higher risk of AKI [OR 3.56, 95% CI 1.40-9.05 (p=0.01)].

CONCLUSION

There was no significant difference in development of ACR or dnDSA within 6 months between lung transplant recipients achieving therapeutic FK506 <7 days vs >7 days. Increased time to dnDSA development in the <7-day cohort suggests a potential benefit to minimizing time to therapeutic FK506 level post-transplantation.

PGY1 PHARMACY RESIDENCY

Corey Dinunno, PharmD

Corey completed his undergraduate coursework and earned his PharmD from the University of Connecticut in 2020. After completion of his PGY1, Corey will be completing a PGY2 in Internal Medicine at Houston Methodist Hospital. Primary project preceptor: Christine Pham, PharmD

Presented at 2020 Virtual Vizient Pharmacy Network Conference; 2021 Virtual Midwest Pharmacy Residents Conference; 2021 Virtual ISHLT Annual Meeting

Evaluation of fluorouracil, leucovorin and oxaliplatin (FOLFOX) chemotherapy dosing in obese colorectal cancer patients

Breanna Hinman, PharmD; Erika Brown, PharmD; Hanna Zaghloul, PharmD; Zhili Fu, PharmD; David Putney, PharmD; Kirk Heyne, MD

PURPOSE

The purpose of this study is to evaluate the safety and tolerability fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy regimen dosing in colorectal cancer patients.

METHODS

This retrospective chart review of colorectal cancer patients receiving FOLFOX chemotherapy. The primary endpoint of this study was to evaluate the safety and tolerability of FOLFOX chemotherapy regimen dosing in colorectal cancer patients with a calculated body surface area (BSA) < 2 m2 compared to patients with a BSA ≥ 2 m2 given capped chemotherapy dosing at 2 m2, and a BSA ≥ 2 m2 given non-capped, weightbased chemotherapy. Tolerability will be defined as the degree to which overt adverse effects of a drug can be tolerated by a patient.

RESULTS

A total of 58 colorectal cancer patients were included with 29 patients having BSA < 2 m2, 24 with BSA of ≥2 m2 non-capped, and 5 with BSA ≥2 m2 capped. There were similar rates of any grade toxicity amongst the groups (86% vs. 88% vs. 100%, p = 0.051), but a higher risk of grade ≥ 3 toxicity was observed with BSA < 2 m2 and BSA of ≥2 m2 non-capped (p=0.026).

CONCLUSION

In our study, dosing practices varied amongst clinicians, and therefore this study could not confirm the benefits of dose capping. Further large studies are needed to assess body weight and its effect on both adverse events as well as clinical outcomes.

PGY1 PHARMACY RESIDENCY

Breanna Hinman, PharmD

Breanna Hinman earned her BS in Biology from University of Georgia in 2016 and PharmD from University of Houston in 2020. Following completion of her PGY1, Breanna will continue her residency training as a PGY2 Oncology Resident at Houston Methodist. Primary project preceptor: Erika Brown, PharmD, BCOP

Presented at 2020 Virtual Vizient Pharmacy Network; 2020; 2021 Virtual Midwest Pharmacy Residents Conference 2021 Virtual HOPA Annual Conference

Description and impact of anti-Xa levels in patients presenting with acute ischemic stroke taking apixaban or rivaroxaban

Olivia Kreidler, PharmD; Kevin R Donahue, PharmD; Tanu Garg, MD; Eric Salazar, MD, PhD; Annette Lista, PharmD

PURPOSE Factor Xa inhibitors (FXaIs) use continues to increase, however there remains residual risk of acute ischemic stroke (AIS). Guidelines recommend against tissue plasminogen activator (tPA) administration in patients whose last FXaI dose was <48 hours. Anti-Xa assays correlating apixaban and rivaroxaban serum concentrations with anti-Xa activity are available and have potential to help guide tPA use in patients with AIS. The purpose of this study is to determine time to stroke intervention, defined as the time to tPA administration or mechanical thrombectomy, in patients taking apixaban or rivaroxaban at the time of AIS. Secondary outcomes of this study included anti-Xa level turnaround time, anti-Xa levels, and rate of major bleeding events.

METHODS

This was a retrospective chart review and included patients presenting with AIS taking apixaban or rivaroxaban.

RESULTS

The final analysis included 225 patients presenting with AIS on apixaban or rivaroxaban therapy. Median time to stroke intervention was 99.5 minutes in patients with FXaI anti-Xa levels and 60 minutes in patients without levels (95% CI -45.1, 76.9; p=0.586). In those with FXaI anti-Xa levels, a total of 6 (15%) patients received intervention, in which 1 (2.5%) patient was administered tPA and 5 (12.5%) underwent mechanical thrombectomy. In patients without FXaI anti-Xa levels, 17 (9.2%) received intervention, in which 1 (0.5%) patient was administered tPA and 16 (9%) underwent mechanical thrombectomy.

CONCLUSION

The results of this study may serve as proof of concept for utilizing FXaI anti-Xa levels in patients with AIS as a means of guiding revascularization therapy.

PGY1 PHARMACY RESIDENCY

Olivia Kreidler, PharmD

Olivia earned her BS in Biochemistry from Texas State University in 2016 and PharmD from the University of Houston in 2020. Following completion of her PGY1, Olivia will be completing a PGY2 in Critical Care at the Medical University of South Carolina. Primary project preceptor: Annette Lista, PharmD, BCCCP

Presented at 2020 Virtual Vizient Pharmacy Network Conference; 2021 Virtual Midwest Pharmacy Residents Conference

Desmopressin versus dextrose in water for therapeutic re-lowering of sodium

Caitlin Labay, PharmD; Kathryn Pidcock, PharmD; Neil Sutaria, MD; Nisarg Gandhi, MD; Hayley Brazeale, PharmD

PURPOSE

Hyponatremia is a common and difficult to correct electrolyte disorder. Safe correction of sodium is essential to prevent devastating neurologic complications. In the event of anticipated or observed overcorrection of sodium, desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) and/or dextrose 5% in water (D5W) may be used to slow the rate of sodium increase. The purpose of this study is to compare the efficacy and safety of these agents in the setting of hyponatremia management.

METHODS

This retrospective, observational study included 369 patients who were treated for hyponatremia (defined by a serum sodium < 130 mEq/L) and subsequently received DDAVP and/or D5W. The primary endpoint of the study was the change in serum sodium within 24 hours of reversal agent initiation (Na24).

RESULTS

The use of both DDAVP and D5W was found to reduce Na24 significantly more than either agent alone (1.5 vs 1 vs -1 mEq/L for DDAVP, D5W, and both, respectively; p < 0.001). This finding was primarily driven by the differences between groups in patients treated with DDAVP in a reactive strategy (those who were given a reversal agent after an observed sodium correction of > 0.5 mEq/L/ hr). The use of both agents was also associated with an increased incidence of rebound overcorrection (1% vs 4% vs 16% for DDAVP, D5W, and both, respectively; p <0.001). The incidence of osmotic demyelination syndrome was assessed via the frequency of head imaging; no differences were found between groups.

CONCLUSION

The use of both DDAVP and D5W is more effective at reducing the rate of correction of serum sodium in the setting of hyponatremia management than either treatment alone. The combination of these therapies may be associated with higher rates of rebound overcorrection following their discontinuation.

PGY1 PHARMACY RESIDENCY

Caitlin Labay, PharmD

Caitlin completed her undergraduate coursework and earned her PharmD from the University of Texas at Austin in 2020. Following completion of her PGY1, Caitlin will begin her PGY2 in Critical Care at Houston Methodist Hospital. Primary project preceptor: Kathryn Pidcock, PharmD, BCPS

Presented at 2020 Virtual Vizient Pharmacy Network; 2021 Virtual Midwest Pharmacy Residency Conference

Characterization of carbaenem-resistent enterobacterales at a large urban health system

Melissa P. O’Neal, PharmD; Katherine Pérez, PharmD; Joshua Knight, PharmD; William Musick, PharmD

PURPOSE

The purpose of this study is to assess the antibiotic susceptibilities of carbapenem-resistant E. coli and K. pneumoniae isolates and develop clinical decision support tools for empiric treatment of CRE. A secondary purpose is to gauge clinical outcomes of patients with CRE, including treatment choice and survival to hospital discharge.

METHODS

We performed a retrospective review of the electronic health record to include all ertapenem resistant E. coli and K. pneumoniae. Repeat cultures and related patient encounters were excluded.

RESULTS This review included 883 carbapenem-resistant (CR) E. coli and K. pneumoniae, of which 10.8% and 45.4% displayed carbapenemase production, respectively. Amikacin, tigecycline, and novel beta-lactam/beta-lactamase inhibitors (BL-BLIs) displayed varying in vitro susceptibility. Prior hospitalization in the preceding 90 days, index visit length of stay, and extended spectrum beta-lactamase (ESBL) production were all significantly higher in the carbapenemase producing cohort.

CONCLUSION

Characterization of these organisms helps streamline empiric treatments prior to finalized AST results. Given variability in resistance mechanisms, phenotypic and genotypic data must be evaluated to adequately represent a population. We identified a large number of highly resistant isolates, primarily in urine cultures, and collected the results of phenotypic testing.

PGY1 PHARMACY RESIDENCY

Melissa P. O’Neal, PharmD

Melissa earned both her BS in Pharmaceutical Science and PharmD from the University of South Carolina in 2020. Following completion of her PGY1, Melissa will continue her post-graduate training as a PGY2 Pharmacy Resident in infectious diseases at Houston Methodist.

Primary project preceptor: William Musick, PharmD

Presented at 2020 Virtual Vizient Pharmacy Network, New Orleans; 2021 Virtual Midwest Pharmacy Residents Conference, Omaha, NE

Evaluation of viscoelastic test-guided blood and factor transfusions in cirrhotic patients

Nina Srour, PharmD; Jesse E. Harris, PharmD; Luma Succar, PharmD; Eric Salazar, MD; Scott Lindberg, MD; Constance M. Mobley, MD

PURPOSE

The purpose of this study is to assess our institutional TEG-guided transfusion practices to understand variables impacting TEG evaluation and correction thresholds.

METHODS

This was a single-center, retrospective study of critically ill, adult cirrhotic patients between May 2016-August 2020. TEGs obtained during the intra- and post-operative periods were excluded. Endpoints evaluated included a description of blood products administered, compliance with the TEG algorithm, and bleeding events. Outcomes were presented per TEG encounter using descriptive statistics.

RESULTS

A total of 116 patients with 559 TEG results met inclusion criteria. Majority of tests were ordered for correction of coagulopathy in non-bleeding encounters (46.5%). Platelets (PLT) were the most commonly transfused products (41.3%), followed by fresh frozen plasma (FFP) (34.9%) and cryoprecipitate (31.1%). Median (interquartile range (IQR)) transfusions per TEG encounter were 1 unit (1–2) for PLT and FFP, and 10 units (10–20) for cryoprecipitate. Rate of compliance with the transfusion algorithm was 31.7%. Non-compliance was mostly driven by maximum amplitude (MA). In a subgroup-analysis of non-bleeding TEGs, under-correction for abnormal K time, -angle, and MA was associated with a significant reduction in packed red blood cell (PRBC) transfusions. Over-correction with FFP and cryoprecipitate was higher when INR was ≥ 2 and fibrinogen < 100 mg/dL, respectively (p<0.01). New thrombotic events occurred in 6 patients and 2 patients had transfusion-related reactions.

CONCLUSION

Despite the availability of TEG results, CCTs continue to influence correction of coagulopathy without reducing bleeding rates. Our review showed that transfusions based on standard TEG cutoffs was not associated with a reduction in PRBC transfusions compared to undercorrections. However, TEG thresholds that can accurately reflect underlying coagulopathy and bleeding risks of cirrhotic patients are yet to be determined.

PGY1 PHARMACY RESIDENCY

Nina Srour, PharmD

Nina earned her PharmD from The University of Colorado in 2020. Following completion of her PGY1, Nina will continue her residency training as a PGY2 Critical Care Resident at Houston Methodist.

Primary project preceptor: Luma Succar, PharmD, BCCCP

Presented at 2020 Virtual Vizient Pharmacy Network; 2021 Virtual Midwest Pharmacy Residents Conference.