Of these, 11 968 people died suddenly and 328 of these died. In this kind of study, researchers would compare the risk of sudden death within seven days of starting co-trimoxazole with the risk in a control period of non co-trimoxazole use in the same patient. In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. In a young patient with good organ function, this is not significant. Co-trimoxazole induced hyperkalemia is common,13 18 can occur quickly,13 19 and can be life-threatening.20 We examined whether treatment with co-trimoxazole was associated with a higher risk of sudden death than other antibiotics used for urinary tract infection in patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Why was its actions on folate metabolism not considered problematic? Whereas nitrofurantoin and norfloxacin are limited to the treatment of urinary tract infection, amoxicillin, co-trimoxazole, and ciprofloxacin are sometimes used for infections at other sites. Ciprofloxacin (which can prolong the QT interval) and nitrofurantoin (which was associated with hyperkalemia in a prior study) were associated with excess sudden-death risks of borderline statistical significance (adjusted ORs, 1.6 and 1.7, respectively). The official journal of The Royal Pharmaceutical Society, International Journal of Pharmacy Practice, Journal of Pharmaceutical Health Services Research. A hyperkalemic crisis can come on so suddenly that even if a conscientious doctor were monitoring serum potassium levels every few months that might not be frequently enough to catch a problem in time. Most of the patients who died were. Thank you for writing this. Our findings derive from patients aged 66 years and older, and the generalizability to younger patients is unknown. In this analysis, we again observed an increased risk of sudden death with co-trimoxazole relative to amoxicillin (adjusted odds ratio 1.54, 1.29 to 1.84). We found that use of co-trimoxazole was associated with an increased risk of sudden death in older patients taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers. But as Ive learned more and more about pharmacology, Im amazed that we dont see more major drug interactions and side effects in folks who take multiple medications. This site needs JavaScript to work properly. Sudden cardiac death is an unpredictable and devastating event, particularly in the young. Be careful out there. If you read Hormones Matter, like it, please help support it. Although we used a validated algorithm to define sudden death,25 some degree of outcome misclassification is likely. As before, all patients would already be taking a RASB. While it is true that some of the enzymes within the metabolic pathways in bacteria are different from those in other cells, they still share a degree of similarity, some 30% sequence homology, suggesting enzymes in these cells will also be affected, though perhaps not as strongly as those in the bacterial populations. Stitcher (Those stakeholders are getting pissed I mean, dont trust computers? Dear Doctor, I would like to express the deepest gratitude to you for writing and updating this website. inflammation of the alveoli of the lungs. Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas. We did a population based nested case-control study of Ontario residents aged 66 years or older receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker between 1 April 1994 and 1 January 2012, the last date for which the vital statistics database was updated. Its down-regulation shifts towards catabolism resulting in muscle wasting. MF, EMM, TG, TA, SH, MMM, and DNJ analyzed and interpreted the data. What it means is that when an older person dies suddenly while taking co-trimoxazole while on a medication like lisinopril or valsartan, no one will figure out why. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Co-trimoxazole is a combination antibiotic drug containing trimethoprim and sulfamethoxazole, prescribed for multiple indications and is the fourth most commonly prescribed antibiotic in the USA.1 Its use has been associated with an increased risk of sudden death among people taking renin-angiotensin system blockers.2 3 This may be owing to acute kidney injury, a rapid . IMS, 2012:46. A standardized difference less than 0.1 indicates good balance between cases and controls for a given covariate.31 We used conditional logistic regression to estimate the odds ratio and 95% confidence interval for the association between sudden death and recent antibiotic use. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). That may be what has been happening with a deadly combination between a commonly prescribed antibiotic and an even more commonly prescribed blood pressure medicine. The primary efficacy outcome was the time to the first event of the primary composite endpoint, which consisted of cardiovascular death, resuscitated sudden death, non-fatal myocardial. Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. Prescriptions disepensed in the community: England 2002-2012. 2013. If this example has you concerned, you may want to read more details in our chapter Drug Interactions Can Be Deadly. There are 11 tips for preventing dangerous drug interactions at the end of the section. IMS Institute for Healthcare Informatics. BMJ. Yes, I would like to support Hormones Matter. Table 1 shows the characteristics of cases and controls. I did not. Bethesda, MD 20894, Web Policies Importantly, ciprofloxacin also tends to be used in patients with more severe or complicated urinary tract infections.38 Whether QT prolongation, severity of illness, or different indications explain the risk associated with ciprofloxacin is unclear. The study authors also found evidence of an interaction between spironolactone and the antibiotic ciprofloxacin (brand names Cetraxal, Cipro), which increased by half a person's risk of sudden death, Antoniou said. cardiac electrophysiologist, cyclist, learner, Changing the use of DrJohnM Facebook page for disease education, Staying Alive Start The Heart Foundation taking off in Louisville, Death-denial is something doctors can change. This was by design, as blocking bacterial folate metabolism makes for a potent antibacterial, which also just so happens, makes it a viable chemotherapeutic. To avoid the potential confounding effects of changes in antibiotic selection and prescribing practices over time, controls were assigned exactly the same index date as cases. We obtained hospital admission data from the Canadian Institute for Health Informations discharge abstract database, which contains detailed demographic and clinical information on admissions, discharges, and same day surgical procedures for all hospitals in Ontario. All Rights Reserved. They should only damage bacteria, while leaving eukaryotic cells unscathed, but they damage mitochondria too (of course they do, mitochondria are ancient bacterium Did anyone think that disrupting the process of DNA replication and reproduction in bacteria wouldnt mess up mitochondrial DNA?). That means it is likely to be ignored by many health professionals. If you are unable to import citations, please contact The fallacies upon which trimethoprim safety was based were that bacteria are completely separate from the humans in and on which they reside, that they are solely responsible for illness, and that pharmaceuticals designed to attack said bacteria would affect only their intended targets. That is, how are Bactrim and other thiamine depleting drugs capable of provoking such a rapid decline into fulminant deficiency? mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. Chandler Marrs MS, MA, PhD spent the last dozen years in womens health research with a focus on steroid neuroendocrinology and mental health. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later. official website and that any information you provide is encrypted Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). Across different research projects, estimates suggest from 30-70% may have insufficient thiamine intake to meet the demands of daily living and given the corresponding rise in chronic health issues of metabolic e.g. weight gain or loss. "Spironolactone is an old drug that's been around for decades, and has shown to greatly impact older adults with advanced heart failure," said Maurer, also a spokesman for the American College of Cardiology. These efforts are ongoing. How many of those 250 million ACE/ARB prescriptions could have been avoided if exercise was seen asa medicine,or if elderly patients had been deprescribed? As far as I can tell, in the 50 years this drug has been on the market, its conformational similitude to thiamine was not considered. Some of the most common names are: These drugs are also included in many combination products. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. Again, these limitations are independent of antibiotic exposure. Computers are fine. Nevertheless, folate deficiency is linked to immune system dysfunction, dermatological issues, cardiovascular dysregulation, and neurologic problems, including sensory neuropathies with axonal damage. The researchers could not determine if there is a causal relationship between the antibiotic and sudden death, but they hypothesize that it may be due to the drugs ability to raise potassium levels. Agree totally! PMC National Library of Medicine This is important because sudden death in patients taking spironolactone may erroneously be attributed to intrinsic heart disease, say the researchers. Now, following second ablation, I am on Tikosyn and Pradaxa. Trimethoprim is given to kill bacteria but it also acts like amiloride, (a potassium-sparing diuretic) in the kidney. THF is essential in one carbon metabolism and the transfer of methyl, methylene, and formyl groups from one molecule to another during the production of nucleotides and amino acids e.g. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Of course, with each passing year I have become incrementally more cautious with everyone from infants to the elderly in hospitals or in public health settings. They noted then that: These findings support the notion of a potentially life-threatening drug interaction between trimethoprim and inhibitors of the renin-angiotensin aldosterone system.. Study highlights how taking trimethoprimsulfamethoxazole and spironolactone together can increase the risk of sudden death in older patients. The site is secure. The blockade of the metabolism and uptake of these two critical nutrients is key to understanding the spectrum of adverse events associated with it, particularly those not directly induced by the sodium channel blockade that causes hyperkalemia. The authors of that prior study theorized that such increased risk of sudden death in the cohort was associated with the quick and clinically significant rise in potassium, which then caused an unrecognized arrhythmic death. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. The story here is not just about the specifics of an important drug-drug interaction. However, this applies equally to all the antibiotics we studied. Importantly, bacterial synthesis of folate and other B vitamins, represents a critical pathway not only for nutrient availability of the human host, but for managing the vast microbial ecosystems in a manner favorable to host survival. The finding of a threefold increased risk of death with cotrimoxazole over amoxicillin in older patients taking ACE inhibitors or ARBs teaches us to consider other antibiotics in these patients. If you ever feel like covering the dangers of fluoroquinolones, I know that everyone going through fluoroquinolone toxicity syndrome would appreciate the attention and acknowledgement. Spironolactone (brand name Aldactone) is a diuretic widely used in treating heart failure. We deemed patients to have discontinued treatment if more than 100 days lapsed between successive prescriptions; in such cases, observation was extended for 100 days from the date of the last prescription. Spotify But taking spironolactone alongside the antibiotic trimethoprim-sulfamethoxazole (brand names Septra, Bactrim) can cause blood potassium to rise to potentially life-threatening levels, said study lead author Tony Antoniou, a scientist with the Li Ka Shing Knowledge Institute at St. Michael's Hospital in Toronto. HHS Vulnerability Disclosure, Help But short-sighted physicians (and others), who dont look at multi-symptom, chronic illness as a possible effect of a class of antibiotics (FQs are chemo drugs masquerading as antibiotics) think that they have a better safety record than sulfa drugs. We thank Brogan Inc, Ottawa, for use of their Drug Product and Therapeutic Class Database. Please be sure to specify the particular web page or function at issue, and provide us with any other information you may think will help us locate the area. WHO model list of essential medicines. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population-based study. Its already 2015. 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