In this episode I’ll:
1. Discuss an article about the effects of antibiotic exposure and infection with resistant organisms.
2. Answer the drug information question “Should a second dose of 4-factor PCC be given to a patient who has refractory bleeding from rivaroxaban?”
3. Share a resource for evidence-based healthcare.
Before we begin, I’d like to share a pearl from my book, A Pharmacist’s Guide to Inpatient Medical Emergencies:
“Don’t hand over an unlabeled med. Tape the vial to the syringe in a pinch if you have to” #pharmacists https://t.co/w0tP1mmQW7
— Pharmacy Joe (@PharmacyJoe) September 7, 2016
Article
Lead author: L. Silvia Munoz-Price
Published in Critical Care Medicine August 2016
Background
Linking antibiotic resistance to drug exposure is important to enhance our understanding of the risks and benefits of antimicrobial therapy. The authors of this study sought to determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii.
Methods
The study was a retrospective cohort of consecutive patients admitted to a single-center trauma ICU over a 23 month period. Patients underwent rectal and tracheal surveillance cultures on ICU admission, then weekly. The primary outcome for the study was positive surveillance cultures for carbapenem-resistant A. baumannii.
Results
12.5% of the 360 patients studied developed a positive surveillance culture for carbapenem-resistant A. baumannii. Two factors were significantly associated with positive surveillance cultures:
1. Each additional point in the Acute Physiologic and Chronic Health Evaluation (APACHE) score increased the hazard of a positive surveillance culture by 4.8%.
2. Time-dependent exposure to carbapenems quadrupled the hazard of a positive surveillance culture.
Further analysis determined that every additional carbapenem defined daily dose increased the hazard of a positive surveillance culture with carbapenem-resistant A. baumannii by 5.1%.
Conclusion
The authors concluded:
Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.
Discussion
This study took place at a single center with endemic carbapenem-resistant A. baumannii. As such, results may not be generalizable to all ICUs. The study looked at surveillance cultures rather than clinical infections. However, the same authors published in 2015 findings that positive surveillance cultures was the strongest variable associated with subsequent development of carbapenem-resistant A. baumannii clinical infections.
Overall, I think this article provides a very strong argument for antibiotic stewardship. Especially knowing that every additional day of carbapenem use put patients at greater risk of a positive surveillance culture.
Drug information question
Q: Should a second dose of 4-factor PCC be given to a patient who has refractory bleeding from rivaroxaban?
A: If an adequate dose of 4-factor PCC was given and bleeding is still serious, consider switching to activated factor VII rather than a second dose of 4-factor PCC.
Shout out to “Pharmacy Claire” for raising this question in the Pharmacy Nation Slack group.
One thing that struck me in some of the 4-factor PCC reversal studies that I’ve read is that hemostasis takes hours to occur after PCC administration. For a life-threatening bleed, hours can be an eternity! The authors of a 2014 article suggest activated factor VII (VIIa) for refractory bleeding from rivaroxaban that does not resolve after 50 units/kg of 4-factor PCC. Unfortunately, a definition of the time frame bleeding becomes “refractory” is not provided in this article. If you do consider factor VIIa, remember that thrombotic risks are much greater when activated clotting factors are given.
Resource
Another shout out to “Pharmacy Gavin” who continues to bring his A-game to my email inbox. This time, Gavin shares an evidence-based health care resource: nntonline.com. This website is maintained by Dr. Chris Cates, a general practitioner and a reviewer and editor with the Cochrane Airways Group. Nntonline.com has information on statistics, systematic reviews, study design, classic examples of evaluating evidence in the context of clinical practice, and much more.
If you have a resource you find useful in critical care or hospital pharmacy practice, please tell me about it at joe@pharmacyjoe.com.
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.
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