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A 24 year old male patient with cystic fibrosis was admitted due to CF exacerbation and flare up. He’s known to have chronic sinusitis, colonized with MRSA and mucoid pseudomonas. New culture from this admission grew out MRSA and Pseudomonas.
Allergy : vancomycin (Redman’ syndrome) & Amoxicillin
Patient’s vital signs were unremarkable with a temp of 35.5c, blood pressure (sbp/dbp) of 105/57 mmhg respectively, heart rate of 89bpm and respiratory rate of 18br/min
His laboratory parameters include a serume creatinine = 0.57 mg/dl and wbc = 9.7 x10 3.
patiet’s home regimen which were documented on his chart are of multitude nature and include: Sertraline 50mg, pancrelipase , omeprazole 20mg, vitamin E and Albuterol inhaler among others.
Upon admission, patient was started on broad spectrum antibiotics which included: linezolid 600mg (vancomycin was discontinued 24hrs after initiated), colistimethate 80mg, ceftazidime 2 gram in accordance to the hospital protocol.
During verification process the pharmacist noted a major drug-drug interaction that occur between two of the patient’s regimen which could cause potentially serious harm. The drugs in question are sertraline, a serotonin reuptake inhibitor widely used in the treatment of depression, and linezolid, an antimicrobial agent used as an alternative to vancomycin to treat MRSA infection.
There’s a well-established medical data that “coadministration of linezolid (MAOI) with serotonergic agents may potentiated the risk of serotonin syndrome, a rare but serious and potentially fatal condition…” Symptomes of serotonin syndrome may include mental status changes such as irritability, altered consciousness, hallucination and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering and mydriasis; and neuromuscular abnormalities such as hyperreflexia, tremor and rigidity.
The Medical Resident who initiated the order was contacted and alternatives were given to avoid the harmful effects which may ensue from such interaction without delaying therapy. One option was discontinuation of Sertraline temporarily until patient’s infection is adequately treated using appropriate clinical parameters. Initiation of another antidepressant agent from a different group would be another option to look into. Unfortunately, most antidepressants on the market. including the tricyclic antidepressants (TCAs) posses serotonergic activities to a certain degree and have been shown to interact with MAOIs significantly.
After reviewing and weighing in the pros and cons in using serotonergic agent along with a monamine oxidase inhibtor; assessing patient’s clinical condition for which he was readmitted and given that vancomycin, the one and best alternative to linezolid in treament of MRSA, could not be used due to intolerance, the discontinuation of sertraline until patient’s overall clinical conditions imporve was deemed the best option.
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One must be careful of abruptly discontinuing SSRI as well as it may cause SSRI withdrawal syndrome. Alternatively you could have still given the patient vanc (if the “allergy” is truly red man syndrome) as this more of a non-immune mediated histamine release, so you can slow the vanc infusion and/or give Benadryl. Also, not sure what the patients allergy is to amoxicillin but ceftaroline (5th gen ceph) also covers MRSA and given that she seemed to have tolerated ceftazidime, it might be ok. Lastly, daptomycin also covers MRSA although need to check a CK before hand as there’s an increased risk of rhabdomyolysis. Good case!
Thanks for your comment. Your point about the potential danger of abrupt withdrawal of SSRI agents is valid and is something that we should avoid if at all possible. As you stated Daptomycin would be a good alternative to consider but it has its downsides. With regard to the use of vancomycin at a slower rate that was actually tried for several doses without success. Patient could not tolerate it even at a 2 hr infusion. Also, at this institution Linezolid is more preferable over Daptomycin for CF patients who need antimcrobial therapy on a chronic basis for several reasons:1. the increased risk of rhabdomyolis you alluded to that is associated with Daptomycin, 2. the availability of Linezolid in an oral form which the latter lacks and, 3.Linezolid may be less costly long term.
Good case and discussion. Sertraline does have a long half-life and discontinuing it may still not avoid a potential reaction. I believe the recommendations are that if the benefits outweigh the potential risks of giving both, to discontinue sertraline and monitor for 2 weeks or until 24 hours after last dose of linezolid, whichever comes first. We usually have good success managing redman’s syndrome by premedicating with benadryl and slowing down the vancomycin infusion, however each patient’s willingness to try it again is different. And daptomycin should not be used in pneumonia because it is inactivated by lung surfactant. Ceftaroline would normally be a good option to consider. We don’t yet know its role in MRSA pneumonia yet but we would expect it to be good like other cephs. But it does not cover Pseudomonas, so in this case, you would still need to figure out how to manage that. And there are no sensible options to add to colistin and ceftaroline. Cefepime, ceftazidime, zosyn (allergy to amoxicillin anyway?) and meropenem are all beta-lactams and wouldn’t make sense to use with ceftaroline. And I’m assuming the Pseudomonas is resistant to quinolones since on colistin. And tobramycin with colistin is a horrible option with poor lung penetration and significant nephrotoxicity.
Too bad we don’t have ceftobiprole yet! (covers MRSA and Pseudomonas) But I’ve heard its approval is being pursued again. Also on the subject, there is a new oxazolidinone that just got approved for ABSSSIs called tedizolid. It did not demonstrate this interaction in seritonergic-model animal studies (patients on seritonergic agents were excluded from Phase 2 and 3 trials comparing to linezolid.) It is still a weak MAOI, but it is theorized that since it is much more potent (dose is 200 mg/day vs. 1200 mg with linezolid), it should not interact with SSRIs at clinically relevant doses.
My head is spinning from the dazzling, respectful discussion…thanks everyone! #medicationeducation is in session!