Does Order of Antibiotic Administration Matter?

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Hello Everyone,

Today I’ll be discussing whether the order of antibiotic administration in patients requiring multiple antibiotics matters. In patients who are critically ill with concern for bloodstream infections, two types of antibiotics are given as standard of care: 1) anti-pseudomonal / broad-spectrum beta-lactam coverage (typically cefepime or piperacillin-tazobactam) and 2) anti-MRSA coverage (typically vancomycin). A 2021 study was conducted to determine whether the order of administration of these antibiotics matters- spoiler: it makes a difference.

Link to study: https://academic.oup.com/cid/article/75/1/98/6381106?login=false

Rationale:
-Early antibiotic administration in sepsis has been proven to reduce mortality. Mortality increases with each hourly delay in antibiotic administration.
-Early in the ED course, patients often have limited IV access. If multiple antibiotics are required, there is no established preferential order of administration.
-Vancomycin takes 1 hour to administer. Cefepime and pipericillin-tazobactam take 15-30 minutes each to administer. Given the hour-to-hour increase in mortality with antibiotic delays, these timings could be significant if one antibiotic is preferential.
-Theoretically, gram negative bacteria may cause more serious infection due to exotoxin release and profound inflammatory response. Broad-spectrum anti-pseudomonal antibiotics may provide better coverage early in infection course over anti-MRSA coverage, which covers for a more narrow spectrum of pathogens.

Clinical Question:
Does the sequence of antibiotic administration in patients with suspected blood stream infection have an effect on 48-hr and 7-day mortality?

Study Details:
-Multicenter retrospective observational study from July 2016-2020 in Baltimore, MD
-N = 3376 patients total
-Inclusion: Patients older than 13, all suspected blood stream infections
-Exclusion: Patients who did not receive at least one dose of antibiotic within the first 6 hours of treatment, overlapping antibiotics, previously on antibiotics, contaminant organisms in blood cultures, and non-bacterial organisms in blood cultures
-Groups: Beta lactam first (including cephalosporin, piperacillin-tazobactam, carbapenems, or monobactams) vs. Vancomycin first

Discussion/Conclusion
-Administration of a beta-lactam antibiotic prior to vancomycin is protective against 48-hr and 7-day mortality (reduced odds of 7-day mortality by 52%)
-Strengths: large sample size, generalizability
-Limitations: retrospective study, non-randomized
-Recommendations: further prospective studies can provide additional evidence

Next time when ordering antibiotics for a critically ill patient with concern for blood stream infection, based on this study, consider the sequence of administration as well (and communicate with nursing!). Prioritizing beta lactam administration may significantly impact mortality for our patients. It’s a simple step, but it can make a big difference.

Best,

Lekha Reddy

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Pediatric vs. Adult Trauma Assessment

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Good Morning Everyone, 

Given our new pediatric trauma protocols at MMC Main, I am providing key differences in the pediatric trauma assessment compared to adults (note: this is not a comprehensive review of pediatric ATLS). While there is significant overlap in the evaluation of adult and pediatric traumatic injuries, there are a few key differences in physiology and anatomy that must be understood to properly evaluate and stabilize a pediatric trauma patient. 

Major Differences between Adult and Pediatric Trauma

  • Weight-based dosing: Utilize Broslow tape (located in Resus 51) to ensure efficient medication dosing and delivery  

  • Allow parents at the bedside during resuscitation to allow for patient comfort and provide explanation of the resuscitation

  • Consider non-accidental trauma when history is vague or inconsistent 

*Pedi STAT is a mobile application providing information on normal vitals, RSI meds, ETT sizing, agitation, burns, PALS, fluid/blood resuscitation, pressors, seizure, GCS, pain management, etc. Great for quick reference! 

Airway

  • If there is a concern for airway stability, below is a diagram detailing the differences in pediatric airway anatomy.

  • How to Optimize: The anatomical differences are adjusted for by elevating the shoulders and backs of young infants/children with a rolled towel or sheet for optimal alignment. 

  • Cricothyrotomy: If indicated, needle cricothyrotomy is for children <10-12 years due to small size of the cricothyroid membrane. Children older than 10-12 years may have an open cricothyrotomy. 

  • Laryngoscope sizing: 

    • 0-2 years: Miller/Mac 1

    • 2-8 years: Miller/Mac 2

    • > 8 years: Miller/Mac 3

  • Endotracheal Tube Sizing: Cuffed = (age / 4) + 3.5; Uncuffed = (age / 4) + 4

  • Endotracheal Tube Advancement: Endotracheal tube size x 3 = Lip Line location

Breathing

  • Pediatric patients have shorter safe apnea times and more sharp O2 desaturations due to differences in physiologic reserve and oxygen consumption. 

  • Oxygenation / Ventilation 

    • Non-rebreather

      • <2 year old: 4L/min

      • 2-12 year old: 6L/min

      • >12: 8L/min 

    • Bag-valve mask ventilation can cause gastric insufflation in children which can quickly compromise ventilation- NG/OG tube should be placed quickly

    • NG tube size = uncuffed endotracheal tube size x 2 

  • What to do for pediatric Tension Pneumothorax: 

    • ATLS recommends Needle decompression in 2nd intercostal space at midclavicular line (differs from adults) 

    • Chest tube size = 3-4 x uncuffed endotracheal tube size 

Circulation 

  • Hemorrhagic shock: Hypotension is a late finding in pediatric hypovolemic shock. Rely on tachycardia or clinical signs of poor perfusion to direct resuscitation. 

  • Lower end of normal systolic BP for various age ranges: 

    • 0-28 days: <60

    • 28 days - 1 year: <70

    • 1 year - 10 years: 70 + (age x 2) 

    • > 10 years: 90 

  • IO Access: Optimal locations include anterior tibia, distal femur, and medial malleolus if IV access unsuccessful 

Disability

  • Consider using GCS or AVPU score to assess for disability 

    • AVPU: Alert, Verbal, Painful, Unresponsive 

    • A score of V or lower correlates to GCS </= 9 

Exposure

  • Pediatric patients have higher risk of hypothermia and coagulopathy due to high metabolic demand and surface area: volume ratio. External warming matters! 

Laboratory Studies

  • Not always indicated in children 

  • For patients who are unstable or with severe injuries: Type and Screen, VBG, CBC, BMP, LFT, coagulation factors 

  • Consider BGM for AMS, pregnancy test for females of reproductive age, UA for hematuria

  • ECG and troponin if concern for blunt cardiac injury

Imaging Indications

  • E-FAST is recommended in evaluation of an unstable child following trauma 

  • CXR / Pelvic XRs only indicated if clinical concern for pulmonary or pelvic injuries

  • CT Scans should be ordered with discretion due to portended malignancy risk from radiation. Consider utilizing risk stratification tools such as PECARN for head trauma. Consult with the peds ED, trauma team and/or PICU colleagues if questions arise. 

Summary of formulas (can also be found in Pedi STAT): 

  • Laryngoscope sizing: 

    • 0-2 years: Miller/Mac 1

    • 2-8 years: Miller/Mac 2

    • > 8 years: Miller/Mac 3

  • Endotracheal Tube Sizing: Cuffed = (age / 4) + 3.5; Uncuffed = (age / 4) + 4

  • Endotracheal Tube Advancement (lip line) = uncuffed endotracheal tube size x 3 

  • Chest tube size = uncuffed endotracheal tube size x 4

  • NG tube size = uncuffed endotracheal tube size x 2 

  • Lower end of normal systolic BP for various age ranges: 

    • 0-28 days: <60

    • 28 days - 1 year: <70

    • 1 year - 10 years: 70 + (age x 2) 

    • > 10 years: 90 

I hope this review was helpful! Any additional pearls / thoughts are welcome as we continue to transition to our new pediatric ED protocols. 

Best,

Lekha Reddy

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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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