Think about tradeoffs. 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. These drugs, which act via the kidney, can increase potassium levels in up to 10% of patients. Careful, John! Both spironolactone and trimethoprim-sulfamethoxazole are individually known to increase blood potassium levels, according to the U.S. National Institutes of Health. However, this applies equally to all the antibiotics we studied. The researchers examined cases of sudden death in those who received an outpatient prescription for co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin within seven days of death. Disruption of these ecosystems involving nutrient depletion results in pathogenesis both of the infectious and oncogenic varieties. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); This site uses Akismet to reduce spam. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. The story here is not just about the specifics of an important drug-drug interaction. Taken together, however, the combination yields potent bactericidal effects. Although I did not spend any time covering Keflex, the second drug prescribed to this individual, I would like to note that it too damages mitochondria, albeit by different mechanisms. lung failure causing loss of breath. 2009; Lakoff et al. Although trimethoprim inhibits dihydrofolate reductase in bacteria, it is estimated that an approximately 50,000 times increased concentration of the drug is required to inhibit the human form of this enzyme.. Trimethoprim-sulfamethoxazole is frequently prescribed for urinary tract infections, with more than 20 million prescriptions written every year in the United States for a variety of infections, the researchers said in background information. Sudden cardiac death is an unpredictable and devastating event, particularly in the young. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a more than twofold increase in the risk of sudden death (adjusted OR 2.46, 95% confidence interval [CI] 1.55-3.90). We carry vast microbial ecosystems whose functions are critical to human survival; vitamin synthesis among them. In sum, it has become compellingly apparent that eukaryotic cells and complex organ systems cannot survive without the synergistic complex interactions of competent enteric bacteria and evolutionarily fashioned mitochondria, but go ahead and just cover him with some Bactrim. sharing sensitive information, make sure youre on a federal If, at any time, you have difficulty using this website, please contact us. SH did the statistical analysis. Thirty years ago as a young nurse I was quite comfortable administering drugs as ordered, and upper ranges of drugs when I was given a range via protocols. Contribute now. Most of the patients who died were. Disclaimer. Although we had no information on indications for antibiotic use, we used a disease risk index to adjust for potential predictors of sudden death. We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. 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. Although I would argue, deficiencies in these two nutrients would exacerbate Bactrims effects on sodium-potassium balance. 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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). Be careful out there. I am now, In using a fictitious example, the mother of a football playing athlete takes an interest in, Dr. Marrs and I became aware of the symptoms and some of the laboratory results in, Over recent years, a number of new diets have become popular among health conscious individuals. In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared those who received of amoxicillin (odds ratio 1.38, 95% confidence interval 1.09 to 1.76 after adjustment). BMJ 2014;349:g6196. In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared those who received of amoxicillin (odds ratio1.38, 95% confidence interval 1.09 to 1.76 after adjustment). Although the study found an association between combined use of spironolactone and trimethoprim-sulfamethoxazole and sudden death in seniors, it did not prove a cause-and-effect relationship. Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. 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. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. and transmitted securely. Mr. Zekowski is always on top of his game. This notion appears to be based upon a study in 1965, where uptake of the drug and subsequent DHT enzyme binding activity in lab grown bacteria (escherichia coli, staphylococcus aureus, proteus vulgaris), in other animal tissue, and in pulverized human liver cells post autopsy from one individual, were compared. Chandler Marrs MS, MA, PhD spent the last dozen years in womens health research with a focus on steroid neuroendocrinology and mental health. There are also limitations to this trial that prevent a definitive answer to what we are supposed to do clinically. Youve written a wonderful piece. For a more in-depth discussion on this paper, check out the editorial hereor this wonderful post on #NephJC. The question one must ask is how presumably healthy individuals develop thiamine insufficiency upon the usage of drugs like Bactrim. They tracked 100,000 people who had received a prescription for one of these blood pressure medications. 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 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. Thats the easy lesson. They searched the Canadian medical database and identified over a million people who had taken either an ARB or an ACE inhibitor during the 17-year study period. 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. As before, all patients would already be taking a RASB. Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. This additive adverse effect would also be expected with any other drug known to cause hyperkalaemia, such as other potassium-sparing diuretics and angiotensin-converting enzyme inhibitors, they say. I ask for clarification more, and I have refused to administer certain drugs without better evaluation. Methods: Theyre not. 2011). Most of the patients receiving spironolactone treatment who died suddenly were 85 years of age or older. It is also involved at the alpha oxidation phase of fatty acids, at the HACL1 enzyme and is critical for the metabolism of the branched chain amino acids, leucine, isoleucine, and valine. Now consider older patients with lifestyle diseases, such as obesity, heart failure, diabetes and high blood pressure, conditions that impair organ function. The vast majority of cases (1027; 93%) were matched to at least one control (3733 controls). Data sharing: No additional data available. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. Ciprofloxacin also had a smaller but still significant increased risk of sudden death compared to amoxicillin (1.29, CI of 1.03 to 1.62). 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. The, No sooner had we landed than my phone began to convulse with a cacophony of bells, 2014-2021 CRM Health & Fitness, LLC. That retrospective study used the administrative health records, spanning 18 years, of more than 200,000 patients prescribed spironolactone. "One of the consequences of a high potassium level is getting these irregular heart rhythms that can be quite dangerous and cause sudden deaths," Antoniou said. I believe these aspects of the drug may underlie many its adverse reactions in addition to, and perhaps compounding, those associated with its propensity to induce hyperkalemia. Why Don't We Listen to Women When They Are Sick? 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. The .gov means its official. There also may be an issue of confounding by indication, as we dont have any data on why these individuals were prescribed these antibiotics. MF, EMM, TG, TA, SH, MMM, and DNJ analyzed and interpreted the data. 2011 Sep 12;343:d5228. Hello,thank you for the information.40 years ago just one Bactrim put me in hospital.All over mucuos membranes were red,open sores and painful.I was student in the university,went to hospital,internal med.dr saw me and called for a consultation from other departmans,they realize it was Bactrim allergy and said I should be in the literature.For one week I could only take water with pipet, going to bathroom was really really painfully was crying. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. Diabetic patients require special consideration, as many of them are especially prone to high potassium levels. Home Sudden Death in Those Taking Bactrim Along with ACE Inhibitors or ARBs, Taking Bactrim with ACE/ARBs Inhibitors cause Death. doi: 10.7326/ACPJC-2015-162-12-013. Sigh. Finally, we checked with two of the best drug interaction resources available on the web. DNJ is the guarantor. Im a student from another country and your blog is a real treasure to me, as it helps me to understand pathological processes and their connection with biochemistry and other academic disciplines better. First published on February 2, 2015 / 3:49 PM. Sadly, there is not adequate awareness about the deadly consequences of this drug interaction. 1, 1994, and Dec. 31, 2011. The answer to that question has to do in part to shoddy research and in part to an economically self-serving framework for understanding human physiology that has since become institutionalized into medical dogma. 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. 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). If you are unable to import citations, please contact Finally, we were unable to reliably determine the dose of trimethoprim, precluding a dose-response analysis. If a page cannot be made accessible, we will work to make a text version available. Stitcher All rights reserved. These findings indicate that intestinal bacteria contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate. Get browser notifications for breaking news, live events, and exclusive reporting. The researchers found that the combination increased the risk of sudden death nearly 2.5 times higher than the combination of spironolactone and amoxicillin. They simply prevent bacterial replication. We are not funded and accept limited advertising. Those of the best drug interaction nearly 2.5 times higher than the combination increased the risk of hyperkalemia when with... Wonderful post on # NephJC the administrative Health records, spanning 18 years, of more 200,000. Be made accessible, we checked with two of the patients receiving spironolactone treatment who died suddenly 85! 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