Emergency Medicine Cases

This section provides a bank of real-life cases in our Emergency Medicine Department that have been selected due to their teaching value. Each case is presented and discussed by our faculty and residents with references to the medical literature.

You are working a minor treatment shift and a 75 yr F who was seen earlier with a right leg cellulitis has returned for her repeat dose of IV Cefazolin prior to her HPTP appointment tomorrow. The patient and her husband are quite upset with having to return since it's now 1am and their HPTP appointment is at 8am. The patient is otherwise healthy, she is not septic and there is no concern for more significant infectious process (i.e. necrotizing fasciitis, abscess).

*What could have been done differently?* (assuming she needed IV antibiotics - whether she did or not is a whole other question that we do not have a good evidence based answer for, unfortunately).  

ANSWER: Using PROBENECID to increasing half-life of Cefazolin and decrease need for patient to return to the ED for antibiotic dosing before HPTP follow-up*

PROBENECID INFORMATION AND EVIDENCE

Probenecid/Cefazolin for Cellulitis
It is possible for most adults with cellulitis to be treated in the community. The usual pathogens are Streptococcus Pyogenes (group A b-hemolytic streptococcus) and Staphylococcus Aureus. The latter causes superficial cellulitis that is typically less extensive than that of streptococcal origin. Staph aureus is more likely associated with open wounds or cutaneous abscesses, though differentiation may be difficult. Approximately 24% of Staph aureus in Calgary ED and Urgent Care Centres (2012) may be b-lactam resistant (MRSA); evaluate this risk based on clinical suspicion or lab confirmation (previous infection or colonization with MRSA).

Although Cefazolin is traditionally administered every 8 hours, the use of Probenecid allows for once daily administration of Cefazolin by inhibiting renal secretion, slowing renal elimination and prolonging the period of therapeutic serum concentrations.

This will allow many patients to be treated without disruption of their normal daily activities (e.g. work, school) and will potentially reduce the overwhelming burden of ED overcrowding and overall healthcare costs.

Dosing:
Adults:Cefazolin 2g IV once daily (also works with Cefotaxime, Cefuroxime, Ceftazidime) with Probenecid 1 gram PO OD given 15 minutes before antibiotics.

Children: (Thank you Mary Lou O’Byrne)
Recommended dose for children over 2 years (25mg/kg + 17%)
Weight Dose Capsule (125, 250, 500mg )
  9 -  12 kg 250 mg 1x250mg
13 – 17 kg 375 mg 1x250mg  + 1x125mg
18 – 22 kg 500 mg 1x500mg
23 – 27 kg 625 mg 1x500mg + 1x125mg
28 – 32 kg 750 mg 1x500mg + 1x250mg
33 – 39 kg 875 mg 1x500mg + 1x250mg + 1x125mg
40 kg & over 1000 mg 2x500mg

Monitor for improvement
The infection may be improving but the symptoms such as redness & inflammation may initially continue to progress because of prior tissue damage (like sunburn: the tissue damage occurs during the day but the erythema and pain present later in the evening).

General care
Elevating the limb is very important and is probably the main reason people who are hospitalized do better than in the community. Encourage rest as much as possible with the affected part elevated i.e. resting on pillow, in a sling, etc. Daily clinic/ED visits at appropriate times to keep to 24 hour drug administration. Check for tolerability/compliance with oral dosages of Probenecid.

Switch to oral regimen
Generally this decision will be made by ID/HPTP clinic. The patient should be reviewed daily with an aim to switch to oral antibiotics within 48-96 hours. Much clinical experience and limited research suggest that a switch from IV to oral antibiotics can be safely made after 3 to 4 days for uncomplicated cases. Signs and symptoms of infection should be improving, with decreases in erythema and induration. Skin wrinkling at the infected site suggests reduced swelling. Body temp and WBC & diff (not required) should show an improving trend. Total treatment length is for 7-14 days.

Benefits
- Cost effective (fewer ED visits, fewer doses of IV antibiotics)
- Patient convenience
- Decreases departmental burden
- Safe and effective

Mechanism of Action:
In the kidney, probenecid reduces the active tubular secretion of drugs by inhibiting organic anion transporters (OATs) in the basolateral membrane of the proximal tubular cells. Thus the clearance of organic anion drugs with a high fu (e.g. ? 0.9; fraction excreted unchanged in the urine) will be reduced leading to an increase in plasma concentration and extended half-life of drugs such as the penicillins and cephalosporins (reference: Clinical Pharmacology Bulletin 2013)

For the visual learner:
MOA of probenecid

https://youtu.be/YYE7yrIqsPg

*Both meds are stocked in the ED and the ED order sets are consistent with these recommendations.
There is some in-vitro and pharmacokinetic studies that suggest that 1gm PO BID provides better drug levels. This is not a controversy that is relevant to us in the ED because:

  1. They will follow up with HPTP or be started on PO ABx,
  2. The consensus from the ID docs in Calgary is to use Probenecid 1gm PO OD,
  3. The tolerability of BID is less (more GI side effects) and,
  4. Probenecid is not available at community pharmacy, making BID dosing impractical.

Contraindications:
- Hypersensitivity to Probenecid
- High dose ASA therapy
- Blood dyscrasias
- Uric acid kidney stones
- Children <2 years of age
- Acute gouty attack
- Peptic ulcer disease
Caution in patients with
- Creatinine clearance < 50mL/min (may not be effective)
- G6PD
- Patients on MTX (significant drub interaction)
- As with all other drugs we use infrequently – I recommend you using a drug interaction program (PEPID, lexi-comp) to check for interactions as they are many.

Adverse Effects:
- Rash, nausea, vomiting      
- Infrequent: headache, dizziness, flushing

EVIDENCE FOR PROBENECID
1.  There is convincing in vitro data (see CADTH review and systematic review below) that shows in probenecid significantly improves the serum Cefazolin levels and increases the half life (2008 CADTH review).

2. One moderate quality (by peds standards) peds study that showed Cefazolin decreased failure rate (30.8% vs 8.2%) in non-facial cellulitis.

3.  Good evidence that Cefazolin + Probenecid is equivalent to Ceftriaxone. I know ID here (and in Edmonton) really do not want us using Ceftriaxone because of resistance concerns (systematic review on the topic and previously cited CADTH review).

4.  There is an Australian study that looked at Cefazolin OD (with Probenecid) vs BID and the outcomes were the same (slightly more side effects in probenecid group but probenecid group allow more patients to be treated as outpatients).

 

A trauma patient was intubated for fluctuating GCS (from GCS 3 to GCS 16 - extra point for directed vulgarity) and vomiting (intubated for airway protection and to facilitate imaging).  During post-intubation, he was either very sedated or very agitated (especially whenever we tried to do anything to him).  We needed to keep him intubated for the time being (he was still intoxicated and had spinal fractures- albeit radiographically stable ones) but I didn't expect him to need to go to the ICU.  The nurses were having a hard time keeping him sedated (I had him on Propofol 20-50mcg/kg/min and a fentanyl infusion - 75mcg/h).  I had no desire (or indication) to paralyze this patient.  Hemodynamics were not an issue.

I received many pages from the nurses about his sedation... they wanted orders for more sedation, so I would "verbally" approve another dose of Propofol bolus (which had usually already been given since they were concerned he was going to extubate himself). They were trying to manage his sedation as best they could; I was trying to manage my other patients.

Learning point:

This patient needed more liberal sedation orders which would have provided nursing staff with some direction and autonomy to either increase his baseline fentanyl infusion or use of PRN Propofol boluses for periodic procedures.  The problem was that I ordered both the Propofol and fentanyl infusions off of the SCM browser, not from within an ED order set (i.e. there were no orders for bolusing of Propofol and no range on the fentanyl dosing).  Had I used the ED Post-Intubation Order Set (also accessible under the ED Head Injury or ED Trauma Order Sets) I would have greatly:  1) improved his sedation, 2) made the nurses’ job much easier, and 3) improved my efficiency (by avoiding having to return to the bedside so frequently).

I have included this EMCRIT podcast which reviews the importance of sedation and analgesia in the Post-Intubation period.  A few components of the order set maybe a bit controversial (i.e. in a 2013 meta-analysis of BZD vs. non BZD: dexmedetomidine, Propofol), the use of BZD was associated with longer ICU stay and longer mechanical ventilation. They provide a good framework for post-intubation management. 

PS.  If anyone has a desire to look at these 2 specific questions:  1) should we avoid BZD in the post intubation period and 2) what is the ideal depth of sedation, I'd be happy to chat with you.

A few other key points (thanks to Lendrum, Betzner and Jason Lord).

1.  Ensure you have a decent approximation of the patients’ weight (an interesting study from years ago showed nurses are better than physicians at predicting patients’ weight).

2.  Ensure no other reason for agitation (i.e. distended bladder, lying on glass/debris, oligoanalgesia, missed injuries)

3. Propofol infusion syndrome is real - Jason Lord discussed a case of patient on only 80mcg/kg/min for <24H who developed worsening lactic acidosis and shock, which resolved with discontinuation of the propofol.

4. Strongly consider using some analgesia (as Weingart describes it - see how comfortable it is to have two fingers jammed in the back of your throat and another stuck into your bladder).  Fentanyl infusion at 1-2mcg/kg is a nice HD stable agent that can be shut off quickly

5.  Consider the addition of small doses of haldol (Mike Betzner recommends 1.25 for frail/elderly and 2.5mg Q5min to a max of 10mg) - maintains resp drive and has a "soothing effect" (not exactly what Mike said but I can't quote him directly).  Consider adding benadryl if >5mg of haldol to avoid dystonic reactions.

6.  Minimize use of paralytics unless necessary:

A. patient protection (i.e. unstable cspine fracture and agitated, imminent risk of self-extubation or severe TBI, facilitate imaging)

B. difficulties ventilating/oxygenating patient (vent asynchrony, ongoing hypoxia) despite optimizing other variables (i.e. right vent settings, O2, bronchodilators, etc).

C. worsening shock/metabolic derangements

Comments?

Shawn Dowling, MD, FRCP

CASE:

You are the "results MD" and amidst the 1700 positive urine cultures you reviewed that day, you come across a Positive C. difficile culture for a 50 year female seen the day before for diarrhea and abdominal pain. She had recently been treated for C. difficile infection (CDI) and just finished a course of Flagyl. The diarrhea had resolved but has since recurred.  

A number of questions come to mind before you call the patient to follow- up these results (beyond did my colleague chart their discharge meds in SEC or is the phone number on the chart going to be right).  

Questions:

1)      How do I treat a recurrent CDI case?

2)      When do I consider PO Vanco and at what dose?

3)      What defines Severe CDI ? Do I treat it any differently?

How do I know which antibiotics my colleague treated the patient with?
Any new or changed medications MUST be included in the ED Discharge – Discharge Instructions Box –. This will create a document in NetCare (along with the discharge diagnosis) which you will be able to review.  This will make your job as a "results MD" much easier and allow for better communication with the primary care physicians.

What about outpatient stool cultures?  

If the patient was unable to provide a stool culture in the ED and you send them home with a stool collection kit, the patient ABSOLUTELY must follow-up these results with their primary care physician since these results WILL NOT get sent back to the ED or SCM.  Alternatively, you can follow-up these results yourself (results will be in NetCare).

Read this 2015 AHS Antimicrobial Stewardship Backgrounder for these answers and more!  If you want more info on C. difficile, check out this Dynamed link, from a computer within the AHS firewall.

Key points:

  1. Stay tuned – C. difficile order set is in the works!  Currently if you want to treat someone for C. difficile, refer to the recommended doses on the attached PDF or go to "Clostridium difficile management" on the SCM browse (the doses are correct on that OS but they are inpatient orders, so PLEASE do not order off of them).
  2. Mortality rate is 3.4%
  3. Treatment for mild/moderate 1st and 2nd episode of C. difficile: Flagyl 500mg PO TID x 10 days.  
  4. If not better at 3-5 days OR >2 episodes of CDI – Vancomycin PO (see dosing on document - it's a bit complicated)
  5. CDI definition of severity: 
  • Infectious Disease Society of America (IDSA) 2010 guideline categorizes Clostridium difficile disease as mild-to-moderate, severe, or severe-complicated*
    • Mild-to-moderate disease
      • white blood cell count (WBC) ? 15,000 cells/mcL or
      • creatinine ? 1.5 times baseline
    • Severe disease
      • WBC ? 15,000 cells/mcL or
      • creatinine ? 1.5 times baseline
    • Severe-complicated disease
      • meets criteria for severe disease plus
      • hypotension, shock, ileus, megacolon, or perforation present

5.  Treatment for severe infections: Vancomycin PO + IV Flagyl

Pediatrics relevant issue:  Generally we don't test for C. difficile in children <1 year of age because they are much more likely to be colonized, rather than infected, with C. difficile.