In this episode, I’ll:
1. Discuss an article about using tigecycline for clostridium difficile infection.
2. Answer the drug information question “Has mycophenolate ever been associated with aveolar hemorrhage?”
3. Share a resource that can be used to determine a patient’s warfarin dose.
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When tigecycyline first arrived on the market it was called a – 1st in class antibiotic – a glycycycline. The drug was accompanied by tigers walking next to doctors in the advertisements, and a black-box warning about increased mortality after a meta-analysis of phase 3&4 trials. This prompted me to look closer at tigecycline. I noticed that tigecycline is structurally identical to minocycline, with an extra 4-carbon chain dangling off one end. I immediately thought:
Because tigecycline is bacteriostatic, has the increased mortality warning, and is essentially minocycline, I have almost never used it in a critically ill patient.
Recently, “Infectious Disease Kris” ordered tigecycline for a patient with recurrent clostridium difficile infection who was unable to receive vancomycin.
This peaked my curiosity, so I had my student research what evidence there was behind such practice. Shout out to “Pharmacy Student Michelle” who came across this article:
Lead author: Stefano Di Bella
Published in International Journal of Antimicrobial Agents in July 2015
This article is an excellent review of available evidence on the use of tigecycline for clostridium difficile infection (CDI).
Some key points found in the article are:
Tigecycline has shown in vitro activity against C. difficile. The authors performed a literature review of in vitro and in vivo studies and case reports on the effectiveness of tigecycline for CDI.
In the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines, tigecycline is mentioned with a recommendation grade C-III (marginally supported recommendation for use—expert
opinion evidence) for severe CDI cases when oral treatment is not feasible.
A few studies have examined the relationship between treatment with tigecycline and proliferation of C. difficile and toxin production. Tigecycline has an inhibitory effect on protein synthesis, thereby lowering toxin A and toxin B levels and preventing sporulation.
Case reports of dozens of patients who used tigecycline for CDI are summarized. 35 patients (74%) were cured, 7 died (15%), 2 had recurrences (4%), 1 (2%) had a clinical failure and 1 (2%) experienced a skin rash.
The usual dosage was 100 mg loading dose followed by 50 mg every 12 h. The duration of treatment ranged from 3 days to 24 days (mean 12 days).
Tigecycline is a potential candidate for the treatment of CDI based on in vitro data, but it may also cause disruption of the normal bowel microflora.
The authors concluded that:
Although more studies are needed to confirm its usefulness in preventing or treating CDI also in consideration of cost/benefit aspects, the available evidence suggests that tigecycline could be an additional option for critically ill patients or cases of refractory CDI.
Drug information question
Q: Has mycophenolate ever been associated with aveolar hemorrhage?
A: Yes, there is 1 case report.
The case report published in 2013 was titled Pulmonary hemorrhage with capillaritis secondary to mycophenolate mofetil in a heart-transplant patient.
The authors stated:
We present a case of a patient who developed acute respiratory failure 7 days after orthotopic heart transplantation and who had been on both mycophenolate mofetil (MMF) and tacrolimus agents. Lung biopsy revealed features of pulmonary hemorrhage with capillaritis. Considered as a possible etiology, MMF was withdrawn. There was immediate improvement of the patient’s symptoms. The temporal relationship between MMF exposure and onset of pulmonary symptoms in the absence of other possible etiologies strongly suggests a causal relationship.
Warfarindosing.org is a free website to help clinicians begin warfarin therapy by estimating the therapeutic dose in patients new to warfarin. The site is supported by the Barnes-Jewish Hospital at Washington University Medical Center, the NIH, and donations.
Warfarin dose estimates are based on clinical factors and (when available) genotypes of two genes: cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1).
Recommendations on warfarindosing.org are based on data from over 1000 patients. The calculations performed on the site explain 53% of the variability in a warfarin dose. If you return to the website and enter an INR value after 3 or 4 warfarin doses, the dose refinement is even more accurate.
I’ve used this site with good success determining appropriate starting doses for warfarin for many patients. I like how I can save my patient’s data and return every day to get a new dose estimate based on the new INR value.
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.