Although trimethoprims thiamine blocking capability was not known until 2017, had anyone bothered to look at the structure of the compound relative to that of thiamine, it would have been obvious. TA is supported by a new investigator award from the Canadian Institute for Health Research and Ontario HIV Treatment Network. lung failure causing loss of breath. Considering that the vast number of medication adverse reactions are rarely identified much less published, almost 1000 papers published suggests something is going on with this medication. In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. MF drafted the manuscript, which was critically revised for important intellectual content by all authors. 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. Each year, more than 50 million prescriptions are dispensed in the United Kingdom and more than 250 million prescriptions in the United States.1 2 These drugs are principally used for the treatment of hypertension, coronary artery disease, congestive heart failure, proteinuria, and chronic kidney disease.3 Both drug classes increase the risk of hyperkalemia, which occurs in up to 10% of patients and is particularly common in patients with other drug and disease related risk factors for hyperkalemia.4 5 6 7, Co-trimoxazole (a combination antibiotic containing trimethoprim and sulfamethoxazole) is commonly prescribed for the treatment of urinary tract infection and is listed on the World Health Organizations essential medicines list.8 Each year, approximately five million prescriptions are dispensed in the United Kingdom and 20 million in the United States.9 10 Trimethoprim has structural and pharmacologic similarities to the potassium sparing diuretic amiloride. Notes on Folate Carriers, Anti-Folate Medications, and Thiamine Deficiency, With Thiamine Paradox Symptoms Patience Is Key. SH did the statistical analysis. Neither trimethoprim nor sulfamethoxazole alone kill bacteria. Thank you for bringing attention to the dangers of cotrimoxazole. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the submitted work as described above; MMM has served on advisory boards and/or received honorariums from Astra Zeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffman La Roche, Novartis, Novo Nordisk, and Pfizer; no other relationships or activities that could appear to have influenced the submitted work. The laws of nature no longer hold true. Sign up to get our weekly updates directly to your inbox: Apple Podcasts We included ciprofloxacin because of its clinical popularity, although it is typically used for more complicated infections and can predispose to sudden death by prolonging the QT interval.26 27 28 We excluded patients who received prescriptions for any other antibiotic in the 14 days preceding the index date, thereby restricting the analysis to patients with only one antibiotic prescription. While most of the adverse effects of this drug are attributed to its induction of hyperkalemia high potassium levels via its blockage of the sodium channels in the kidneys, I think that is only part of the story. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics. Trimethoprimsulfamethoxazole and risk of sudden death among patients taking spironolactone. But they arent free. Copyright 2023 BMJ Publishing Group Ltd, Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study, http://creativecommons.org/licenses/by-nc/3.0/, www.who.int/medicines/publications/essentialmedicines/en/, The Royal Surrey NHS Foundation Trust: Locum Consultant in Oncology, Swansea Bay University Health Board: Locum Consultant in Plastic & Reconstructive Surgery, Brent Area Medical Centre: Salaried GP - Brent Area Medical Centre, Minehead Medical Centre: GP Consultant - Minehead Medical Centre, Meadows Surgery: GP Opportunity (up to 8 sessions) - The Meadows Surgery, Ilminster, Womens, childrens & adolescents health, for the Canadian Drug Safety and Effectiveness Research Network (CDSERN), Correspondence to: D N Juurlink, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue G106, Toronto, ON, Canada, M4N 3M5. I would like to take this opportunity to thank you and all the lawyers involved at your firm who worked diligently and tirelessly to bring about the positive result in my case. In a case-control study of more than 1.6 million patients over 17 years, researchers from Canada found that cotrimoxazole was associated with a three-fold increased risk of sudden death when used in older patients (age > 66) taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). All told, folate is integral for healthy cell function and proliferation, mitochondrial respiration and epigenetic regulation. Agree totally! The date of death served as the index date for all analyses. Although other combinations of sulfonamides are available with trimethoprim, TMP-SMX is by far the most widely used. Methods: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone . We identified patients treated with either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker between 1 April 1994 and 1 January 2012, excluding patients who received both drug classes simultaneously. PMC A few years back, I had a confirmed UTI (P. mirabilis). Young healthy patients have organ reserve. Trimethoprim/Sulfamethoxazole Is Associated with Sudden Death in Patients Who Take Renin-Angiotensin Inhibitors Paul S. Mueller, MD, MPH, FACP, reviewing Fralick M et al. Ill be more cautious when prescribing trimethoprim-sulfamethoxazole, especially in those taking ACE-inhibitors and ARBs. I developed lesions on my tongue (blood gorged papules) and peeling skin on my genitals. it has been demonstrated that major classes of bactericidal antibiotics, irrespective of their drug-target interactions, induce a common oxidative damage cellular death pathway in bacteria, leading to the production of lethal reactive oxygen species (ROS) (412) via disruption of the tricarboxylic acid (TCA) cycle and electron transport chain. National prescription audit. These efforts are ongoing. We do not capture any email address. In a general sense, this study gives me pause because cotrimoxazole carries such a benign reputation. Sorry for going off on my tangent about FQs. The BMJ 2011; 343:d5228. Among older patients treated with ACEIs or ARBs, the use of trimethoprim-sulfamethoxazole is associated with a major increase in the risk of hyperkalemia-associated hospitalization relative to other antibiotics. Nitrofurantoin was associated with a lower risk of sudden death for the seven day analysis, but not the 14 day analysis. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. Canadian researchers have been concerned about the combination of the antibiotic co-trimoxazole with ARBs or ACEIs for years. We used administrative data and did not have access to serum potassium or creatinine concentrations, adherence to treatment, non-prescription drug use, and other risk factors for sudden death. weight gain or loss. Nowhere on the death certificate will it say, This patient died because of a drug interaction mistake.. Funding: This study was supported in part by a grant from the Canadian Drug Safety and Effectiveness Research Network (CDSERN) and by the Institute for Clinical Evaluative Sciences (ICES), a non-profit research institute sponsored by the Ontario Ministry of Health and Long-Term Care (MOHLTC). We're empowering you to make wise decisions about your own health, by providing you with essential health information about both medical and alternative treatment options. 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). By Lisa Bebell, MD, Contributor. We believe health information should be open to all. Although I would argue, deficiencies in these two nutrients would exacerbate Bactrims effects on sodium-potassium balance. When trimethoprim was originally discovered and yet still, medicine believed that bacteria were somehow entirely separate from the organism in which they resided. If you read Hormones Matter, like it, please help support it. This is an important question, because sudden death due to hyperkalemia in the pre-hospital setting is likely to be misattributed to intrinsic heart disease, particularly in older patients with existing cardiovascular disease or diabetes.17. We excluded cases that could not be matched to at least one control. I had the rapid heart rate, insomnia , indigestion, and the worst still after finishing is my red gums, red and sore tongue. When appropriate, alternative antibiotics should be considered in such patients. Introduction. I admit I entered medical school suspicious of medications ability to restore or maintain true health. National Library of Medicine Bactericidal antibiotics, as a class of drugs and irrespective of specific mechanisms of action, fundamentally and sometimes irrevocably, damage mitochondria. This is addition to a spectrum of neuropsychiatric manifestations from depression to dementia that are associated with this critical nutrient. A recent study on the common antibiotic cotrimoxazole, which is a combination of sulfamethoxazole and trimethoprim, and often referred to by its brand name, Bactrim or Septra, lends credence to the notion that combining drugs can be dangerous. Over a 17-year period, almost 12,000 people died suddenly -- 349 of them within 14 days after taking either trimethoprim-sulfamethoxazole or another antibiotic. There is a growing movement to identify pediatric and young adult athletes who may be at risk for sudden cardiac arrest (SCA) or sudden cardiac death (SCD) during sports participation. You can find it in our book, Top Screwups Doctors Make and How to Avoid Them. Cotrimoxazole is also a commonly used antibiotic, with up to 50 million prescriptions written each year. 2015 Canadian Medical Association or its licensors. 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. Overcast First published on February 2, 2015 / 3:49 PM. As before, all patients would already be taking a RASB. Methods: Podcast Addict The researchers matched each case with up to four controls and found that sudden death was more than twice as likely for those taking trimethoprimsulfamethoxazole as for those taking amoxicillin (adjusted odds ratio [OR] 2.46, 95% confidence interval [CI] 1.553.90). That is why, the most serious conditions associated with thiamine deficiency are wet and dry beriberi and Wernickes encephalopathy, the condition for which Fedratinib contains a black box warning. Now, following second ablation, I am on Tikosyn and Pradaxa. You are doing an amazing job and helping lots of people with it! Data sharing: No additional data available. The importance of our findings is underscored by the fact that co-trimoxazole is prescribed to millions of patients taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Control patients were required to be alive at the index date and, like cases, received one of the study antibiotics in the seven days preceding the index date. 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). Most of the patients who died were. Unrecognized severe hyperkalemia may underlie this finding. Now consider older patients with lifestyle diseases, such as obesity, heart failure, diabetes and high blood pressure, conditions that impair organ function. Trimethoprim-sulfamethoxazole was linked to sudden death in older patients using spironolactone. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index. It goes by many names. Please! Many people think trimethoprimsulfamethoxazole [co-trimoxazole] is a fairly innocuous drug with not a lot of side effects, says Tony Antoniou, lead author on the study and a pharmacist at St Michaels Hospital in Toronto, Canada. The default to pharmacologic treatment needs to change. In other words, an awful lot of people are vulnerable to this potentially deadly drug combination. Did you also note that the authors said millions of patients receive this antibiotic in combination with ARBs or ACE inhibitors? I much prefer deprescribing. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. [1] Antoniou T, Hollands S, Macdonald EM et al. Bethesda, MD 20894, Web Policies 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? KEEP UP the GREAT work John! In a case-control study of more than 1.6 million patients over 17 years, researchers from Canada found that cotrimoxazole was associated with a three-fold increased risk of sudden death when used in older patients (age > 66) taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. A recent study found a risk of sudden death among patients taking trimethoprim-sulfamethoxazole. 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. 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. However, the sudden death of a young nonathlete is no less tragic. The importance of our findings is underscored by the fact that co-trimoxazole is prescribed to millions of patients taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Of these, 11 968 people died suddenly and 328 of these died. It was an impossible task. 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. For each case, we identified up to 4 controls matched by age and sex. If you are unable to import citations, please contact In the primary analysis, co-trimoxazole was associated with a significantly increased risk of sudden death within seven days relative to amoxicillin (unadjusted odds ratio 1.83, 95% confidence interval 1.50 to 2.24), and this result persisted after adjustment using the disease risk index (1.38, 1.09 to 1.76). 2013. Nevertheless, it was well known that Bactrim blocked folate, that folate was critical to human health, and that its deficiency could wreak havoc on health. This medication is a combination of two antibiotics: sulfamethoxazole and trimethoprim. official website and that any information you provide is encrypted This is important because sudden death in patients taking spironolactone may erroneously be attributed to intrinsic heart disease, say the researchers. We closely follow guidance from the World Wide Web Consortium. So now you can see the problem. If ones diet is high in sugars, supplemented with coffee or tea, and/or if alcohol is consumed regularly, the path to thiamine deficiency is expedited. 2007b). Social connections impact our health in profound ways, whether it, Do we need an RCT to establish the worth of, Two weeks ago on the GeriPal podcast we talked about, Psychedelics are having a moment. doi: 10.1136/bmj.g6196. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are among the most commonly prescribed drugs in clinical practice. 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