Anecdotal evidence of improvement following anti-fungal treatment As some of your may recall, when Graham McPhee was in hospital with recurrent sepsis, his son @IanMcPhee reported that he had been prescribed anidulafungin (an IV antifungal drug), following which he noticed improvement in his long-term ME/CFS symptoms as well as the acute symptoms for which he was admitted to hospital. (See: https://www.s4me.info/threads/updates-on-graham-mcphees-health.17583/page-15#post-331376) After Graham was discharged from hospital, I wrote to him privately to ask him whether he thought the anidulafungin had had any effect on his ME/CFS symptoms. Graham was typically helpful and forthcoming. As he indicated that he was happy for me to share the details of what we discussed, with the permission of Ian and his mum, I have pasted some excerpts from my private conversations with Graham in a separate post below. In summary, Graham noticed a marked improvement in his ME/CFS symptoms following a 10 day course of IV anidulafungin, which he was prescribed along with IV antibiotics when he was in hospital with recurrent sepsis and Covid-19. Initially he noticed improvement in his sinus symptoms and headaches. Later he noticed a marked reduction in PEM, despite having had recurrent sepsis for 18 months and a nasty Covid-19 infection at the age of 71. I was particularly interested in Graham’s experience because I have had some improvements – including improvement in sinus symptoms – after courses of different oral antifungal drugs. Following my conversations with Graham, I asked two of my former consultants if they would be willing to write to Pfizer to ask if they would be willing to supply anidulafungin free of charge for a case study. One kindly agreed, but Pfizer was not willing to help. They were however interested enough to write to me to ask me to complete a form to record adverse events and unexpected therapeutic benefits, which I did with the help of Ian and his mum. At that time, I mistakenly thought Pfizer owned the patent for anidulafungin. However, I subsequently discovered that the patent has expired which means there would be little or no incentive for them or any other pharmaceutical company to invest in any trials. The benefit of it being out of patent is that it is less expensive but I understand the cost would still be about £1200 per week + the cost of administering it, which would probably be in the region of £4000 per week at a private hospital (if it was possible to find a private physician willing to prescribe it). Had Pfizer been willing to fund an open label case study, I would have been interested to try it, as I am desperate to try any treatment that has a low probability of making me worse – even if the probability of it helping is very low. However, I doubt that I would pay to have it privately at this stage – although I haven’t ruled it out. [If the cost was £10,000 and the chances of it having a significant beneficial effect were more than 1%, that would equate to less than £1 million for a 100% change of significant benefit.] The reason for posting here is to put the information in the public domain and to see if anyone has any thoughts about it – particularly whether anyone can conceive of how or why it might have had a therapeutic effect. (I will post some links to relevant papers that Graham sent me in a separate post below.) I have already written privately to some ME/CFS researchers about it, including Simon Carding and Chris Armstrong. They both noted the information with interest but neither would be able to do a case study without a prescribing physician, and neither is in a position to take it further at this stage.
Excerpts from conversations with Graham: Me: “Graham, Out of interest, do you think the IV anti-fungals they gave you in hospital might have made any difference to any of your ME symptoms? I appreciate that isn’t a very scientific question, and I wouldn’t ask it publicly, but I’d be interested to know nevertheless” Graham: “Always feel free to ask: I'm a happypotamus, remember. My answer to that is rather lengthy and I was wondering about posting it up as a thread. So instead I'll try it out on you and see what you think. Back in August 97 I went down with some sort of a mild bug while on holiday in York. After that I developed constant pain around both eyes, tracking along my upper jaw, and spreading down both sides of my neck. My GP said it couldn't possibly be sinus problems because of the neck pain. Over the counter medication did absolutely nothing. Generally the pain was background stuff, like the start of a toothache. Sometimes though it became unbearable. This went on for 16 months, and eventually I saw an ENT specialist who put me in for the full rhinoplasty (in my terms, a rebore, decarb, and straightening up). I ended back up in hospital twice because it wouldn't stop bleeding, and I had already lost a lot of blood in the operation. Eventually I was sent home, and developed a high temperature and felt pretty ill. That was the day the ME started (with me, the clearest odd signs are to do with my legs – cold, aches, nerve pain), But the headaches had gone. Well, for 5 years, then they started tracking back again but only on the right side of my face. A while afterwards I went down with polymyalgia rheumatica and was put on steroids – prednisolone. Then, of course, the dose was steadily reduced. I would get down to about 10mg, then the headache would start to niggle. By 7.5mg the headaches were troublesome, so I'd go back to 10mg. I'd try all sorts of different approaches, but nothng seemed to work, so I was on 10mg pretty much steadily from 2005 to recently. In hospital they were all expressing concern about me being on steroids. I'd explain the reason, but nothing really seemed to register, just that I was on steroids. They would come up with ‘helpful’ suggestions like cut down by 1mg per month. Gee whizz Batman, I wish I'd thought of trying that! Anyway, they were scratching around trying and failing to find the source of my negative gram e-coli infection (it was resistant to all but two IV antibiotics). I said that if they were starting to consider unusual possibilities, how about the sinuses. ‘Oh no, can't be…’ But I explained that the Mayo centre had published reports that they had found infections in people with long-term sinus trouble, but masked by a fungal infection: the fungal infection seemed to protect the bacterial infection. ‘Ah but this is an e-coli infection: you don't get them in sinus infectionse’. I mentioned that there had been a couple of studies in India where chronic sinus infections were found to containd e-coli, possibly pneumococci I thought. I don't know what happened then, but they didn't follow it up, and were about to discharge me when I tested positive for covid. To be honest, I don't remember much of the next fortnight, but I know they put me on IV antifungal treatment along with IV antibiotics, and when I ‘came to’ after the covid, the background niggle of pain around my eye had gone. When up in the covid ward they put me on a different form of steroids, and I didn't realise that they were so very much more powerful. So when they were about to discharge me, and told me I was on 6.5mg and they planned to wean me off over the next three days and send me home, I was happy to give it a go. I found out later that it was the equivalent of 44mg of prednisolone. So I had a rotten start back home, and it took me a couple of weeks to work out what had happened. I decided to go back to 15mg, which sorted out a lot of the problems, and since then have slowly reduced it. I'm now down to 7.5mg, with no headaches. Not only that, but my sinuses are clear, and I am blowing my nose a lot. I still have the usual brainfog. My upper body feels remarkably fine, and I am using my muscles quite robustly for an old man of 71 who is recuperating. As I say, my legs are still a problem, and it will take a long time to build back up to my previous standard. It's hard to say about the brainfog, but not having the sinus-headache in the background all the time makes a world of difference. I do sleep a lot more. I sleep from midnight to around 9,00 with some stirrings. Then another hour from 12 to 1, then often another hour from 5 to 6. I'm not fully asleep for all of that time, but I definitely need bed rest. So there you are. A full description. Over to you. Is there anything there of interest, or is it really just a one-off? I'm wondering about fungal/bacterial infection in the sinuses affecting the vagus nerve, in turn sending a message to the brain that I am ill. If so, how long could it take for it to realise that it has gone?” ----------------- Graham: “I didn't experience any side-effects with the IV anti-fungal, but then for much of that time I was out of it with covid. Congratulations on working through such a long ramble. If using my experience can help you in any way in your own search for medical help, feel free.” ----------------- Graham: “I've started pottering around in the garden, and as long as I don't do too much walking, I'm amazed at how much I can do without payback. Some days I have managed a couple of hours or more (in sessions) of reasonably demanding arm and shoulder work, with the usual aches at the end of the day for someone who has been pretty inactive for a year. But no payback the next day! It's brilliant. Some days I have managed a couple of hours or more (in sessions) of reasonably demanding arm and shoulder work, with the usual aches at the end of the day for someone who has been pretty inactive for a year. But no payback the next day! It's brilliant. There must be some reason behind this all. One day someone will discover why.” ----------------- For anyone who isn’t aware, after 18 months of recurrent sepsis with multiple hospital admissions, Graham contracted clostridium difficile (C. diff) and died in hospital in October 2021. (See In Memory thread here: https://www.s4me.info/threads/graham-mcphee.22685/)
These are the links that Graham sent me of studies which report finding infections masked by fungal infections in people with chronic sinus symptoms, and also some studies which reported finding e-coli in the sinuses, as that was relevant to his case: 1) Mayo Clinic Study Implicates Fungus As Cause Of Chronic Sinusitis: https://www.sciencedaily.com/releases/1999/09/990910080344.htm 2) OPD case of chronic pansinusitis of e. coli in ongoing case of chronic allergic rhinitis and sinusitis: http://medcraveonline.com/JOENTR/JOENTR-04-00098.pdf 3) e-coli in sinus: https://www.steadyhealth.com/topics/e-coli-in-sinus 4) Microbiological analysis of paranasal sinuses in chronic sinusitis – A south Indian coastal study: https://www.sciencedirect.com/science/article/pii/S209007401300056X 5) Intra-operative biopsy in chronic sinusitis detects pathogenic Escherichia coli that carry fimG/H, fyuA and agn43 genes coding biofilm formation: https://pubmed.ncbi.nlm.nih.gov/29570706/
I’ve similarly had a longer course if oral anti fungal (not specifically for ME but something else , although it had been mentioned for that quite a bit earlier and declined) I had a lot on at that time that would mean it wasn’t easy to assess if my health improved because well I was snowed under but suspect that it was important at the time in stopping me declining
There have been a number of reports of various interventions in the nasal cavity being useful for ME/CFS and LC e.g. the most recent one. Novel Oro-Nasal Drainage for Long COVID: Proposed Mechanisms – Case Report, 2024, Lorenz et al I've not really taken them seriously, especially the ones that involved abrasion resulting in bleeding. I think the nasal cavity microbiome hasn't been investigated much in ME/CFS though. I remember saying to a doctor that I wish there was a way to have my throat looked at/swabbed/biopsied when it gets sore, as part of PEM, the doctor saying 'but there is nothing to be found there', and me thinking, 'but you can't know that'. For what it is worth, when I have been exerting for too long, the lymph nodes around my head swell and become sore. There is the issue of causal versus downstream. I will often get a cold sore or an infection of some sort when in PEM, and a fungal infection might be a similar reaction to being in a generally bad state. But, there could still be a case for treatment. I see @Snow Leopard suggested that the (temporary) benefit that people report from aripiprazole might be due to its antifungal effect. SL, can you elaborate? Is an antifungal delivered by IV likely to be markedly better than an anti fungal delivered orally? A trial involving oral antifungals would probably be easier. At one stage, the idea of candida infections as a cause was very popular in ME/CFS circles. Was there ever any trials of antifungals done?
Could it have been the antibiotics (assuming these were administered concurrently) or even steroids, which it seems were given at that time? These improvements in ME/CFS after antibiotics seem to be documented quite frequently in the patient community.
I think that is unlikely as he was given IV antibiotics on multiple occasions over the course of 18 months. The improvement followed the 10 day course of anidulafungin (and Covid) which he’d never had before. Similarly, he had been on various doses of steroids for a long time. NB I have been careful not to say that the anidulafungin caused the improvement. All we know is that Graham reported a significant improvement following the treatment. To me, given the lack of leads, that is interesting enough to wonder whether the possibility of it having a therapeutic effect for at least some people with ME/CFS should be investigated. [edited typos]
Relief of 10 yrs 1st memorable thing that helped me was nystatin powder. Calf pains of 10 yrs standing gone within 1-2 days, and only mild and short-lived relapses. Stiffness of movement quickly improved. Whether this related to the result of moving a harmful pathogen or to the process (e.g. immune stimulation sufficient to cause a knock on effect on another more aggravating pathogen), or sth else I do not know. I reject the theory of gut stabilisation since other antifungals azole have helped too However any of this might be, antifungals have helped me. Whatever anyone her might think of Teitelbaum or the late Andy Wright they were in their repertoire as potentially beneficial and noted in numerous anecdotal reports. Unfortunately fungal infrction was over-touted for a while as "ME" which was as stupid as this thata or the other BPSand psycho being "the long awaited answer or common sense"or whatever.
