Types of inhalers:
- Respimat SMI (soft mist inhaler)
- MDI (metered dose inhaler) +/- spacer
- DPI (dry powder inhaler)
Types of inhalers:
Example: you have a lovely 68-year old male with a history of two episodes of C. difficile infections after getting antibiotics in the setting of a hip surgery three months ago. He is admitted to your service with pneumonia and you decide he should get a 5-day course of levofloxacin. He has no abdominal pain or diarrhea (yet). Would PO vancomycin would help prevent recurrence of C. diff?
In this case, the answer is a weak “yes.” There is no randomized controlled trial data showing that PO vanc prevents recurrence. However, there is a retrospective study of 172 patients in Quebec with a diagnosis of C. diff who were exposed to antibiotics for whatever reason within 90 days of their diagnosis. Those patients who had at least one recurrence of C. diff who got PO vanc had half the risk of getting C. diff again. Because the study looked at patients within 90 days of diagnosis, it’s unclear whether patients who had C. diff from a longer time ago would get the same benefits. A second study from 2016 of over 200 patients showed that patients who got PO vanc had a 4% risk of recurrence, whereas patients who didn’t had a 27% risk. Notably, this study only surveilled patients for 4 weeks after their antibiotic course, and the patients weren’t randomized–I got the sense that the patients who were offered PO vanc were “sicker.”
The regimen that I have seen most often is 125 mg PO vancomycin QID, but the second study, for example, reported 125 mg PO vancomycin BID or daily, so regimens are all over the place.
How long should patients continue PO vanc prophylaxis for? Again, no strong right answer. I have seen patients told to take PO vanc for only as long as they are on other antibiotics, for a week after finishing, or to do a slow taper/pulse down. However, there is a clinical trial that has set the time course of PO vanc as 5 days after stopping other antibiotics, which sounds pretty good. What if it’s longer than a week, or a month? I did have a patient who required lifelong oral suppressive antibiotics…and we made the decision to keep her on PO vanc lifelong as well.
Do probiotics prevent recurrence of C. diff? The 2018 IDSA guidelines cite unclear evidence on whether probiotics prevent recurrence. While probiotics are fine for the general population (might as well try it if it won’t hurt), there are rare cases of fungemia/invasive infection that have been reported, in patients who are immunocompromised, have PICC lines, or are otherwise severely ill.
Fecal microbiota transplant (FMT) is an effective and durable method of treating recurrent or refractory C. difficile infections. There are several routes of administration:
Is there any difference between these different routes of delivery? Capsules were first devised at Massachusetts General Hospital; clinical trials are ongoing and they are not widely available. NG tube vs. endoscopy have been compared, and although some have not found a difference, some conclude that endoscopy is superior. For example, this study of 50 patients from the University of Alabama at Birmingham showed that patients who had endoscopy delivery of FMT had a greater rate of “cure” (improvement of symptoms in 2 weeks) and fewer repeat FMT treatments. However, you do have to evaluate each patient individually: some patients may find the idea of an NG tube too repulsive, some may be too sick to undergo endoscopy, etc. Importantly, FMT is felt to be safe for immunocompromised patients, too.
Tangent: according to the 2018 IDSA guidelines for treatment of C. diff, PO vancomycin or fidaxomicin are now considered agents of choice for a first episode of C. diff, no matter the severity. Keep your metronidazole on the shelves! It’s no longer recommended.
It is a widely held belief that Tylenol (acetaminophen, or paracetamol, depending on where you are) should not be used in patients with chronic liver disease or transaminitis because the drug will worsen liver injury or cause acetaminophen toxicity, the most common kind of drug-induced liver injury. However, underuse of Tylenol may lead to overuse of other pain medications, like NSAIDs or opiates, which come with their own problems.
This review in the British Journal of Clinical Pharmacology goes through studies of healthy adults and adults with liver disease, including cirrhosis to look at the evidence for our fear of Tylenol. Essentially, the studies on Tylenol are small, and ALT naturally fluctuates (thus some of the previous methodology linking rise in ALT and Tylenol may have been questionable). The authors conclude that heavy alcohol use, malnutrition/fasting, underweight status, and sepsis may put patients at risk for acetaminophen toxicity, but Tylenol is still not 100% contraindicated for these groups. They state:
We have not found any case reports of hepatotoxicity secondary to therapeutic doses of paracetamol in adults with pre‐existing CLD who did not have at least one of these risk factors.
Therapeutic dose of acetaminophen is 4 g/24 hours. Therefore, it’s recommended that if you have patients with the above risk factors, aim to give them 2-3 g/24 hours. If they are developing rapidly deteriorating liver function (acute liver injury or failure), then it might be time to stop.
(image from Cornell, Dove Medical Press, 2014)
Green=first line, yellow=second line, pink=third line
The eye-“itis”es can be pretty confusing for those of us who don’t regularly use an ophthalmoscope to visualize changes in blood vessels, free-floating cells, deposits, and detritus. (The last time an internal medicine resident diagnosed uveitis on slit lamp/fundoscopy was…? Sorry to my ophtho friends.) Here are some slides I made to help distinguish the “itis”es (organized from anterior to posterior):
***N.B.: One important cause of “red eye” not discussed here is ACUTE ANGLE CLOSURE GLAUCOMA. Conjunctivitis is also not discussed.
Immunotherapy may also be referred to as “checkpoint inhibitors” because these drugs override the immune system’s mechanisms of restraint to increase recognition and activation of an immune response against tumor cells. A great metaphor is that CTLA-4, PD-1, and PD-L1 inhibitors “take the brakes off,” allowing the immune system to “rev up” to fight cancer .
However, as anyone who has ever studied autoimmune disease knows, an overactive immune system can cause damage of its own. Immunotherapy can cause side effects that range from mild to life-threatening in virtually every organ and system; if side effects are severe that is an indication to halt treatment. The decisions on how to manage these toxicities (immune-related adverse effects) are complicated, and while there are guidelines on when/how to treat, the most important part is recognizing a toxicity in the first place–so keep an eye out.