The ACORN Trial- Cefepime vs. Piperacillin-Tazobactam

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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

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How Much Do CT Scans Increase Malignancy Risk?

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Good Evening Everyone, 

One of our most utilized tests in the emergency department is the CT scan. CT scan use in the emergency department has risen disproportionately (330%) in comparison to the increase in ED visits (30%) between 1996 and 2007. In the back of most EM physician’s minds is typically whether radiation is necessary or not, particularly when a patient is young. Today, I’ll be discussing circumstances that have led to rising CT scan usage, evidence for projected malignancy risk, and interventions to address CT overuse.

What are the circumstances causing increased CT usage? 

A systematic review in the American Journal of Emergency Medicine in 2018 examined studies between 1998-2017 and identified determinants associated with increased CT usage in the emergency department. 

  • Increase in defensive medicine practice by physicians 

  • Trauma patients that are transferred from a local ED to a level 1 trauma center are often re-imaged

  • Lack of integration between electronic medical records when patients are transferred between EDs 

  • Rising elderly patient population with more medical comorbidities 

  • ED crowding resulting in less time at the bedside to educate patients on risks of radiation from CT scans 

How much do CT scans increase the risk of malignancy?

A landmark study published in JAMA Internal Medicine in April 2025 established future risk of malignancy with the current rise in CT scan usage using a validated predictive radiation risk tool developed by the National Cancer Institute. 

  • In the study, 61.5 million patients underwent 93 million CT scans from 2023-2024 with the following demographics: 

    • 25.7 million (4.2%) children

    • 58.9 million (95.8%) adults

    • 32.6 million (53%) female

    • 28.9 million (47%) male 

  • There could be 103,000 projected lifetime cancers from radiation-induced malignancy (could account for 5% for all future cancer)

    • Higher CT utilization in adults accounted for most projected radiation-induced cancers (93,000)

      • The CT Abdomen Pelvis is projected to be the cause of the majority of future cancers (37%) followed by the CT Chest (32%) in adults 

      • Most common projected malignancies in adults include lung cancer, colon cancer, leukemia, and bladder cancer

    • Radiation risk is higher in children due to increased physiologic sensitivity to radiation, but projected cancer numbers are lower compared to adults (9700) 

      • CT Head contributes to the largest number of cancers in children (53%), greatest at age <1 with risk decreasing with age 

      • Most common projected malignancies in children include thyroid, lung, and breast cancer 

    • In female patients, lung and thyroid cancer are predicted to have a higher incidence and breast cancer is the second most common projected cancer from CT scan overuse

Interventions to Address CT Overuse In the ED: 

A 2022 systematic review in the Annals of Emergency Medicine identified successful and less successful interventions to address CT overuse in the ED. 

  • Successful interventions without compromising patient safety:

    • diagnostic pathways

    • alternative imaging options

    • involving consultants early 

  • Less successful interventions not backed by evidence: 

    • family/patient education

    • passively disseminated guidelines

    • clinical decision support tools 

All in all, the information above may not come as a surprise to many of us, but it provides us with concrete evidence demonstrating that CT overuse in the ED may have serious consequences for our population (103,000 predicted cancer diagnoses accounting for 5% of all future cancers). Consider the data when ordering your next CT scan and the suggested interventions above so that we may mitigate malignancy risk in the future. 

Best,

Lekha Reddy 

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Blood is thicker than water

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Hello all, this week's video of the week is a spooky bloody one inspired by this past Halloween weekend! 

Brought to you by Dr. Gabriela Hernandez and Dr. Victor Wong!

ED Course

61 y/o female with PMHx of HLD presents to the ED for worsening suprapubic pain x5 months. Several months ago she had an MRI which revealed free fluid in her pelvis.  States that she had an outpatient ultrasound done 4 days ago which revealed persistent fluid in the pelvis and she was sent home with pain medication and antibiotics. Associated symptoms are subjective fever, pelvic pain with walking, and dysuria. Reports history of C-section x1 and D&C. Denies nausea, vomiting, diarrhea, chest pain, vaginal bleeding, vaginal discharge.

Ultrasound

In this still image from clip 1, there is some free fluid around a distended uterus that is filled with heterogenic complex fluid that may be a mass or coagulated blood.

In the 2 attached clips, clip 1 shows a sagittal distended uterus with complex fluid, likely blood clots with trace amount of free fluid in the pelvis. Clip 2 shows the transverse view of the uterus again with complex fluid.

Formal ultrasound obtained by the team revealed: Markedly distended uterus containing complex fluid. Considerations include endometrial carcinoma vs. extensive blood clot. Possibly infection/pyometrium in the appropriate clinical setting.

Conclusion:

OBGYN consulted. They recommended obtaining tumor markers and close follow-up with her outpatient GYN.

Learning Points:

Appearance of blood on ultrasound can be variable depending on age of clot

  • Acute, fresh blood

    • Often hypoechoic or anechoic, may resemble simple fluid early on

    • Can have internal echoes that swirl with probe pressure

  • Organizing / clotted blood:

    • Becomes heterogeneous, with low-to-medium echogenicity

    • Often appears as avascular, nonshadowing, ill-defined material

    • Can seem like a “soft tissue–like” mass that lacks internal vascularity on color Doppler

    • Echogenicity tends to increase as the clot ages and fibrin organizes

  • Chronic clot:

    • Can become retracted and hyperechoic, sometimes mimicking a fibroid or retained products

References:

Patel, S. J., Feldstein, V. A., & Filly, R. A. (2021). Sonographic differentiation of retained products of conception, blood clot, and intrauterine masses: Diagnostic challenges and clinical implications. Emergency Radiology, 28(3), 527–534. https://doi.org/10.1007/s10140-020-01865-6

Radiopaedia contributors. (2025). Blood clot (ultrasound). Radiopaedia.org. Retrieved from https://radiopaedia.org/articles/blood-clot-ultrasound

Nassiri, S., & Lerman, J. (2017). Ultrasound features of pelvic hematomas: Recognizing blood in disguise. Ultrasound Quarterly, 33(1), 40–47. https://doi.org/10.1097/RUQ.0000000000000265



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