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. In contrast, we observed no increased risk of sudden death with the other antibiotics (table 3). 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. Enthusiasm is brimming. Copyright 2023 CBS Interactive Inc. All rights reserved. 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). 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. I was first diagnosed with severe osteoporosis when I was thirteen years old. I learned a long time ago that as we age and loss neurons we also lose nephrons and thus many drugs eliminated through the kidneys behave differently in the elderlynever learned about the epithelial sodium channel in the distal tubuledid learn about the caution on prescribing in the elderly from my dad and Morton Ward early (ca. We identified prescription drug claims by using the Ontario drug benefit database, which includes prescriptions dispensed to all Ontarians aged 65 years or older. NHSBA, 2009. How can it hurt?. Sudden death is found among people who take Bactrim ds, especially for people who are male, 60+ old, have been taking the drug for < 1 month. Sigh. Ciprofloxacin was also associated with a marginally lower but significant risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62). They looked for cases of sudden death and discovered that patients who had also received co-trimoxazole were significantly more likely to have died within 14 days than those who received the penicillin-type antibiotic amoxicillin. Here are just a few examples: Avalide, Capozide, Exforge, Hyzaar, Lotrel, Micardis HCT, Tribenzor, Twynsta and Valturna. It also occurs twice in the pentose phosphate pathway (PPP), the alternative glucose oxidation pathway that provides nicotinamide adenine dinucleotide phosphate (NADPH) and ribose 5-phosphate (R5P) for glutathione, nucleic acid, and fatty acid synthesis and steroid hydroxylation, respectively, making thiamine necessary for not only ATP production, but required for duplication and detoxification processes. Several intestinal bacteria in the colon, but also in the small intestine, are capable of biosynthesis of natural forms of folate as well as vitamin B12 and other B-vitamins (Camilo et al. 2015 Canadian Medical Association or its licensors. This material may not be published, broadcast, rewritten, or redistributed. More than 250 million prescriptions are dispensed in the US each year. However, we dont have any data on serum potassium concentrations. A significant proportion of sudden deaths in the young are unexplained-no cause is identified either during life or at post-mortem. Pocket Casts Data sharing: No additional data available. The .gov means its official. In a supplementary analysis designed to test the robustness of our findings, we removed congestive heart failure (a known risk factor for sudden death) from the disease risk index and incorporated it as an independent term in the conditional logistic regression model. 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. Prescriptions disepensed in the community: England 2002-2012. They come with tradeoffs, and, the more drugs we use together in a patient, the more tradeoffs we should expect. Antoniou, who is also a clinical epidemiologist at the non-profit Institute for Clinical Evaluative Sciences, was prompted to conduct his research after reading reports of high potassium levels associated with this particular drug interaction. However, the sudden death of a young nonathlete is no less tragic. CastBox Taken together, however, the combination yields potent bactericidal effects. By binding DHT, dihydrofolic acid (DHF) and then tetrahydrofolic acid (THF) are blocked. / HealthDay. We conduct ongoing accessibility reviews and remediate any functionality issues. 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. These efforts are ongoing. Co-trimoxazole is a widely used antibiotic. Likewise, how many of the 50 million patients treated with cotrimoxazole had a viral, not bacterial, infection? DNA synthesis and repair. You never know when a particular combination will produce a lethal outcome.. Experts estimate that over 250 million prescriptions are written for angiotensin receptor blockers (ARBs) and ACE (angiotensin converting enzyme) inhibitors. Combining a common antibiotic with an even more common blood pressure medicine can result in sudden death. This study, published in the BMJ last year, included residents of Ontario, Canada, 66 and older and were treated with ACE-inhibitors or ARBs, GeriPal reports. In the 1970s there were no computers for physicians or pharmacists to use to check for dangerous interactions and there were few references available to check out a possible problem. In fact, mixing medicines is very much like playing Russian roulette. But, I have so many great articles published in 2014 that I need to post about! This was only recently discovered by accident. This is a crazy world where one plus one equals three, where down may very well be up and surely pigs have wings. Im stopping this medication ASAP and taking a full dose of thiamine today. The question one must ask is how presumably healthy individuals develop thiamine insufficiency upon the usage of drugs like Bactrim. 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. The prescribing of co-trimoxazole with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) results in a sevenfold increase in the risk of hospital admission with hyperkalemia relative to amoxicillin, Case reports have shown that this drug interaction can cause life threatening hyperkalemia, In older patients receiving ACE inhibitors or ARBs, co-trimoxazole was associated with an increased risk of sudden death; this may reflect sudden death from unrecognized severe hyperkalemia, When patients receiving ACE inhibitors or ARBs require an antibiotic, clinicians should either select antibiotics that do not contain trimethoprim or limit the dose and duration of trimethoprim based therapies, while closely monitoring the serum potassium concentration. Thiamine is, after all, in most enriched and fortified foods. Results: Of the 11968 patients who died of sudden death while receiving spironolactone, we identified 328 whose death occurred within 14 days after antibiotic exposure. Youre starting to sound like a doctor. What are you thinking? mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. 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. They tracked 100,000 people who had received a prescription for one of these blood pressure medications. Youtube When clinically appropriate, alternative antibiotics should be considered in these patients. See: http://creativecommons.org/licenses/by-nc/3.0/. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. 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). But the trimethoprim not the sulfamethoxazole can also elevate potassium levels and cause an interaction, he says. However, this applies equally to all the antibiotics we studied. Drug interactions are the Achilles heel of the medical profession. Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. Go ahead and just cover him with some Bactrim. There are also limitations to this trial that prevent a definitive answer to what we are supposed to do clinically. 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). For each case, we randomly selected up to four controls from the same cohort, matched on age (within 1 year), sex, and the presence or absence of kidney disease and diabetes, recognized risk factors for hyperkalemia and sudden death.29 30 Each control could serve as a control only once, although they were eligible to become a case at a later date. Had he been older and/or carried additional comorbidities, he might not have survived. Get in together, will you? Main outcome measure Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. Antibiotic use and risk of sudden death within seven days. weight gain or loss. weakness or heaviness of the legs. The, No sooner had we landed than my phone began to convulse with a cacophony of bells, 2014-2021 CRM Health & Fitness, LLC. We assure you that this interaction is just the tip of the iceberg! Why was its actions on folate metabolism not considered problematic? More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. Conclusions In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Background: Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics. 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. Values are numbers (percentages) unless stated otherwise. 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. This is addition to a spectrum of neuropsychiatric manifestations from depression to dementia that are associated with this critical nutrient. 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). Folate deficiency during pregnancy is associated with serious neurodevelopment aberrations including neural tube defects like spina bifida and thus Bactrim should be strongly contraindicated for pregnant women, but at least one small study found that 3.2% of the pregnant women sampled were prescribed Bactrim. Trimethoprim-Sulfamethoxazole Increase Risk of Sudden Death. 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. Characteristics of cases and controls. Thank you for writing this. 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? We excluded cases that could not be matched to at least one control. The cases were those who had sudden death and who received an outpatient prescription for either co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin within 7 days of death. 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. It goes by many names. MF, EMM, and SH acquired the data. Finally, we were unable to reliably determine the dose of trimethoprim, precluding a dose-response analysis. Spotify When appropriate, alternative antibiotics should be considered in such patients. Cotrimoxazole is also a commonly used antibiotic, with up to 50 million prescriptions written each year. More importantly, however, and this speaks to the fallacy of separateness that medicine holds dear, at any given time, we carry with 36 pounds of commensal bacteria that are responsible for a myriad of functions, including protective responses that prevent colonization and invasion by pathogens, the inhibition of growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites and importantly, for our purposes, the synthesis and metabolism of vitamins to be used by the host; the very pathways blocked by these antibiotics. Its about the approach to treating people with diseases. Most of the patients who died were. 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. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population-based study. 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. Case reports have also confirmed life-threatening high potassium levels with the combination. of sudden death using a disease risk index. 2015 HealthDay. 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). These drugs, which act via the kidney, can increase potassium levels in up to 10% of patients. TORONTO, ON The risk of sudden death went up by more than a third in older patients taking ACE inhibitors or angiotensin-receptor blockers (ARBs) who were also put on the antibacterial agent. This combination antibiotic is prescribed for urinary tract, respiratory, digestive and skin infections, to name just a few of its many applications. At doses used in clinical practice (typically 80-160 mg twice daily), trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, impairing renal potassium elimination.11 12 Approximately 80% of patients receiving co-trimoxazole develop increases in serum potassium concentrations of at least 0.36 mEq/L and 6% develop frank hyperkalemia (potassium >5.4 mEq/L).13, We have previously shown that the use of co-trimoxazole with angiotensin converting enzyme inhibitors or angiotensin receptor blockers results in an almost sevenfold increase in the risk of hyperkalemia related hospital admission relative to amoxicillin.14 Case reports show that this drug interaction can cause life threatening hyperkalemia,15 16 but whether it can increase the risk of sudden death in clinical practice is unknown. Tradeoffs are truth. 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