Overview of the PRN

The ACCP Critical Care PRN, founded in 1992, optimizes pharmacotherapy outcomes through promoting excellence and innovation in clinical pharmacy practice, research, and education. To achieve this, the PRN provides members with timely educational updates, opportunities to participate in multicenter research, and a forum for information sharing among a network of over 1500 critical care pharmacists and trainees nationally.

PRN Leadership

• Susan E. Smith, Pharm.D., FCCM, BCCCP: Chair
• Zach R. Smith, Pharm.D., FCCP, BCPS, BCCCP: Chair-Elect
• Nicole M. Palm, Pharm.D., FCCM, BCCCP: Secretary-Treasurer
• Keith M. Olsen, Pharm.D., FCCP, FCCM: Board Liaison
• Melissa L. Thompson Bastin, Pharm.D., Ph.D., FCCP, FCCM, BCCCP: Member-at-Large
• Christy C. Forehand, Pharm.D., FCCM, BCCCP: Member-at-Large

Opportunities and Resources for Trainee Members

The Critical Care PRN welcomes all trainees (students, residents, and fellows) and encourages activity and engagement in each of its committees: Communications, Membership, Programming, Recognition, Research, Social Media, Trainee Engagement, and Travel Awards. Each committee is led by a chair and chair-elect and consists of trainee members and clinical pharmacists who collaborate throughout the year on various committee charges. One additional opportunity for involvement is serving as the trainee liaison. Each year, one trainee member is selected to serve on the Critical Care PRN Steering Committee as a liaison and advocate for other trainee members. Applications for this position typically open in September, so be on the lookout!

The Trainee Engagement Committee provides support in recruiting and maintaining trainee members. Each year, PGY2 critical care and PGY2 emergency medicine residency program directors are provided information on free Critical Care PRN membership that can be distributed to PGY2 residents. This committee also coordinates an annual feedback survey specifically for trainee members to better optimize involvement opportunities, initiatives, and resources throughout the Critical Care PRN. Initiatives include the Trainee Member Quarterly Spotlight, which highlights outstanding achievements of a selected trainee member; the Trainee Poster Practice Session, where trainee members can practice their poster presentations and receive feedback before the ACCP Annual Meeting; and “X” Journal Clubs, which are developed and facilitated by trainee members together with a mentor. The PRN provides an annual “Keeping Up with the Literature” document aimed at providing strategies and resources for staying current with medical literature and guidelines. To help identify critical care and pharmacy-related conferences for presenting trainee research project work, the PRN compiles a Conferences and Abstracts Guide with important dates and deadlines to ensure trainee members can plan accordingly.

The Critical Care PRN values trainee member engagement within the profession and provides financial support to do so. The PGY2 Critical Care Resident Research grant offers financial support for residents conducting innovative critical care pharmacy research. In addition, two Critical Care PRN Student Travel Awards and two Critical Care PRN Resident/Fellow Travel Awards are available each year to offset costs for attending and presenting research at the ACCP Annual Meeting. The PRN is active on social media (X: @accpcritprn; Facebook) and encourages trainee members to engage in and network through these platforms! The Critical Care PRN started an Annual Meeting mentor-mentee program this past year that pairs first-time meeting attendees with an experienced PRN member to help the mentee get the most from attending the Annual Meeting.

Current Issues: Acute Kidney Injury Risk from Combining Vancomycin and Piperacillin/Tazobactam

Prepared by: Amoreena Most, Pharm.D., BCCCP

Background

Acute kidney injury (AKI) affects 30%–60% of patients admitted to the intensive care unit (ICU) and is associated with increased morbidity and mortality.¹ Strategies to prevent the development and progression of AKI in critically ill patients include fluid optimization and avoidance of nephrotoxins. Intravenous vancomycin combined with piperacillin/tazobactam is a commonly administered antibiotic regimen in critically ill patients for empiric gram-positive, gram-negative, and anaerobic coverage when infection is suspected. However, the nephrotoxicity associated with this combination, particularly in the ICU setting, has been a question of ongoing research and debate in recent years.^2–4 Evidence surrounding the nephrotoxicity risk associated with combining vancomycin and piperacillin/tazobactam continues to emerge, challenging our previous understanding of this clinical topic.

Mechanism of Nephrotoxicity

Vancomycin administration is associated with a higher risk of kidney injury.⁵ Vancomycin-associated AKI may occur from acute tubular necrosis, acute interstitial nephritis, or a combination of both mechanisms. In contrast, piperacillin/tazobactam is considered a pseudo-nephrotoxin because it increases serum creatinine through inhibiting organic anion transporters 1 and 3 without reducing glomerular filtration rate.⁶

Current Data

Early evidence from multiple observational studies showed an increased AKI risk from administering vancomycin and piperacillin/tazobactam in combination.^2–4 These studies were limited by defining AKI through an increase in serum creatinine without demonstrating a difference in the use of renal replacement therapy. A prospective, observational study of critically ill adults⁷ examined the impact of vancomycin and piperacillin/tazobactam on renal function by comparing changes in cystatin C and creatinine concentration. Cystatin C is unaffected by tubular secretion and may allow for a more precise assessment of renal function. In patients receiving vancomycin and piperacillin, creatinine-defined AKI was higher at day 2 (RR 1.34; 95% CI, 1.01, 1.78) than in patients receiving vancomycin and cefepime. No significant differences were observed in cystatin C change (-5.36; 95% CI, -18.19, 8.86), dialysis (RR 0.63; 95% CI, 0.31, 1.29), or mortality (RR 1.05; 95% CI, 0.79, 1.41).

The most recently published study to investigate the nephrotoxicity of piperacillin/tazobactam was the Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial, which compared the risk of AKI in adult patients receiving cefepime versus piperacillin/tazobactam.⁸ Patients were randomized in a 1:1 ratio to receive cefepime or piperacillin/tazobactam in the emergency department or medical ICU. At the time of enrollment, 942 patients (77.6%) in the cefepime group and 997 patients (76.9%) in the piperacillin/tazobactam group were also receiving intravenous vancomycin. Clinicians continued vancomycin for a median duration of 2 days (IQR 1–4 days). Highest stage of AKI or death by day 14 did not differ (OR 0.95; 95% CI, 0.80, 1.13) between the cefepime and piperacillin/tazobactam groups, nor did major adverse kidney events at day 14 (10.2% vs. 8.8%, absolute difference 1.4%; 95% CI, -1.0% to 3.8%). Patients receiving cefepime experienced significantly fewer days alive and free of delirium and coma than patients receiving piperacillin/tazobactam (11.9 days vs. 12.2 days; OR 0.79; 95% CI, 0.65–0.95).

Conclusions

Accurately identifying nephrotoxic agents remains a key strategy to mitigate AKI development in critically ill patients. Evidence continues to emerge suggesting combination therapy with vancomycin and piperacillin/tazobactam has no clinically significant impact on AKI risk, challenging existing paradigms.

References

1. Pickkers P, Darmon M, Hoste E, et al. Acute kidney injury in the critically ill: an updated review on pathophysiology and management. Intensive Care Med 2021;47:835.

2. Bellos I, Karageorgiou V, Pergialiotis V, et al. Acute kidney injury following the concurrent administration of antipseudomonal β-lactams and vancomycin: a network meta-analysis. Clin Microbiol Infect 2020;26:696-705.

3. Avedissian SN, Pais GM, Liu J, et al. Piperacillin-tazobactam added to vancomycin increases risk for acute kidney injury: fact or fiction? Clin Infect Dis 2020;71:426-32.

4. Blair M, Côté JM, Cotter A, et al. Nephrotoxicity from vancomycin combined with piperacillin-tazobactam: a comprehensive review. Am J Nephrol 2021;52:85-97.

5. Sinha Ray A, Haikal A, Hammoud KA, et al. Vancomycin and the risk of AKI: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2016;11:2132-40.

6. Campbell RE, Chen CH, Edelstein CL. Overview of antibiotic-induced nephrotoxicity. Kidney Int Rep 2023;8:2211-25.

7. Miano TA, Hennessy S, Yang W, et al. Association of vancomycin plus piperacillin-tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study. Intensive Care Med 2022;48:1144-55.

8. Qian ET, Casey JD, Wright A, et al. Cefepime vs piperacillin-tazobactam in adults hospitalized with acute infection: the ACORN randomized clinical trial. JAMA 2023;330:1557-67.