Good Evening Everyone,
Happy Monday! Today I’ll be discussing the ACORN (Antibiotic Control of Renal Outcomes) Trial. Link for full study: https://jamanetwork.com/journals/jama/fullarticle/2810592
Purpose:
- To determine whether the use of cefepime or piperacillin-tazobactam increases the occurrence of AKI or neurologic dysfunction in adults hospitalized for acute infection
Rationale:
- Hospitalized adults with acute infection are often initiated on antibiotics providing:
1) MRSA coverage: typically vancomycin
2) Anti-pseudominal coverage: typically cefepime OR piperacillin-tazobactam
-Bacterial coverage: Similar efficacy in both cefepime and piperacillin-tazobactam has been established
-Side Effects: AKI is a known side effect of piperacillin-tazobactam especially in combination with vancomycin; neurologic dysfunction is a known side effect of cefepime
Study Details:
- Conducted at Vanderbilt University Medical Center between Nov 2021 - October 2022
- Single-center, randomized control trial (N=2511)
- 7% ED patients, sepsis most common diagnosis
- Inclusion criteria: Adults 18 and over in the ED or MICU
- Exclusion criteria: Medication allergy, treatment with anti-pseudomonal coverage in last 7 days, determined by clinician that one of the treatment options was more optimal for the patient
- Two experimental groups: Randomized to either cefepime or piperacillin-tazobactam within 12 hours of hospital stay
- Primary outcome: Highest Stage of AKI or death by Day 14
- Secondary outcomes: Incidence of AKI at Day 14; Number of days alive and free of delirium and coma within 14 days
Results:
-No statistically significant difference in primary outcome when comparing cefepime and piperacillin-tazobactam (AKI stage or death by day 14)
-Piperacillin-tazobactam is not associated with increased AKI or death (even when given in combination with vancomycin)
-Cefepime is associated with increased delirium and coma when compared to piperacillin-tazobactam
Conclusion:
-In adult patients hospitalized with sepsis, since cefepime and piperacillin-tazobactam have similar efficacy, barring contraindications, piperacillin-tazobactam is the preferred agent for anti-pseudomonal coverage as it is not associated with worse neurologic outcomes
Strengths:
-Large randomized control trial with sound methodology
-Addressed clinically important question surrounding two antibiotics commonly used in adults with sepsis
-About 50% of enrolled patients were already with known kidney injury at baseline; thus, a study with a population that was more prone to kidney injury showing no worsening of kidney injury by either antibiotic demonstrates the strength of the conclusion
Limitations:
-Single center study limits generalizability
-No blinding in study which could affect subjective physician assessments of neurologic status
-Clinicians could exclude patients from enrollment if determined that one antibiotic choice was more optimal for the patient- those who suspected potential renal injury from piperacillin-tazobactam may have excluded patients who would have otherwise developed worsening kidney injury, which could have altered the primary outcome
-Short overall treatment duration of antibiotics that varied for every patient based on clinician decision-making (median 3 days), which may have been too short of a duration to allow for development of AKI or neurologic decline
Every institution has its own protocols for antibiotic coverage for hospital-acquired infections, and these protocols should be adhered to. If anyone has further thoughts or opinions on this subject, please do share!
Best,
Lekha Reddy