In this episode I’ll:
1. Discuss an article about using metronidazole in mild Clostridium difficile infection.
2. Answer the drug information question “What is captisol-based amiodarone?”
3. Share a tip for responding to inpatient medical emergencies.
Lead author: Haley J Appaneal
Published in the journal Clinical Infectious Diseases December 2018
The recent update to the C Diff guidelines abandoned the use of metronidazole as monotherapy for C diff of any severity. The authors of this study sought to identify whether metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients.
This was a two-stage study of a national cohort of Veterans with a first episode of mild CDI. In the first stage, the authors identified predictors of success among patients with CDI treated with metronidazole. Success was defined as an absence of all-cause mortality or recurrence 30-days post-treatment. Multivariable unconditional logistic regression was used in this stage.
In the second stage, a subgroup of patients with characteristic(s) predictive of success identified in the first-stage was selected and clinical outcomes were compared with patients who also received vancomycin.
In the first stage, among 3,656 patients treated with metronidazole, the authors identified 3,282 patients with success and 374 patients with failure. Age 65 years and under was the only independent predictor of success with an odds of success 1.63 times higher than age >65 years.
In the second stage, among 115 propensity-score matched pairs 65 years of age or younger, no significant differences were observed between metronidazole and vancomycin for all-cause mortality, CDI recurrence, or failure.
The authors concluded:
Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.
At first glance, this study looks to support the use of metronidazole as monotherapy for mild CDI cases in younger patients.
However, it is important to note there were several risk factors for failure associated with metronidazole identified in the first phase. These included a principle diagnosis of CDI, current intestinal infection, current respiratory failure, malignancy, previous hospital or long-term care exposure, hypoalbuminemia, body mass index (BMI) > 30 kg/m2, and previous probiotic exposure.
In my opinion, any consideration of using metronidazole as monotherapy should take into account patients younger than 65 that do not have any of the predictors of failure mentioned. This makes the decision to use metronidazole as monotherapy more complicated than simply looking at patient age.
Drug information question
Q: What is captisol-based amiodarone?
A: Captisol is a cyclodextrin compound that improves the solubility of amiodarone. Captisol replaces the previously used solvent polysorbate 80, which was associated with hypotension and histamine release in dogs and human studies.
Shout out to podcast listener Dan for bringing up this question in regards to the updated ACLS anti-arrhythmic drug guidelines making mention of a study using captisol-based amiodarone.
The brand name associated with captisol-based amiodarone is Nexterone, and the formulation is 150 mg / 100 mL or 360 mg / 200 mL. This means that boluses of amiodarone prepared from the 50 mg/mL IV vials may have a different side effect profile than premixed captisol-based amiodarone.
Tip for Responding to Inpatient Medical Emergencies
When taking care of a patient with ACE inhibitor-induced angioedema, only 1 thing matters:
Protect the airway with endotracheal intubation.
I don’t get distracted by other therapies which do not have a clinically meaningful effect:
Epinephrine doesn’t work in ACE inhibitor-induced angioedema.
Neither does diphenhydramine, methylprednisolone or ecallantide.
Fresh frozen plasma might help – but you need to thaw it first… and that takes too much time to be practical.
Icatibant only affects meaningless endpoints like edema, not the need for intubation or mortality.
I just focus on protecting the patient’s airway. Within 24 to 72 hours they’ll be extubated and ready to go home.
To get a copy of my 6 best tips for pharmacists responding to inpatient medical emergencies, go to my free download area. It’s number 16 on the list.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.