Tradeoffs are truth. Every drug which works to effect positive change can have potentially disastrous results when poorly selected or administered during a vulnerable period of time for a particular patient. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). In reality, however, there are a number of serious side effects associated with it including: A review published in 2011, identified 925 papers on the adverse effects of trimethoprim and sulfamethoxazole through 2011. Thank you for writing this. 2015 Jun 16;162(12):JC13. Thats the easy lesson. An interaction between the commonly prescribed antibiotic co-trimoxazole and blood pressure drugs such as lisinopril or valsartan can cause sudden death. We are neither separate from our bacterial communities nor are our vitamin synthesis pathways sufficiently distinct from bacteria that we can target a pathway in one without affecting the other. 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. Folate, or vitamin B9 is essential for DNA synthesis and repair. FOIA Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. Im stopping this medication ASAP and taking a full dose of thiamine today. Bactrim, a combination of two antibiotics, trimethoprim and sulfamethoxazole, was first approved in 1968 and 1973 in Canada and the US, respectively and has become a mainstay in pharmaceutical medicine. Importantly, thiamine sits atop these processes, as a gatekeeper of sorts. But, I have so many great articles published in 2014 that I need to post about! (Those stakeholders are getting pissed I mean, dont trust computers? Pocket Casts She has published and presented several articles on her findings. As before, all patients would already be taking a RASB. Antibiotic prescribing excluding topical antibiotic preparations. Be careful out there. 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. A recent study has shown an association between sudden death in those who were given the antibiotic trimethoprim-sulfamethoxazole (Bactrim) while already taking renin-angiotensin system blockers (ACE-inhibitors) or angiotensin receptor blockers (ARBs), heart medications. It included residents of Ontario who were 66 years of age or older and were treated with an ACE-inhibitors or ARBs. The cause of death will likely be assumed to be of natural causes such as a heart attack. Bactericidal antibiotics, as a class of drugs and irrespective of specific mechanisms of action, fundamentally and sometimes irrevocably, damage mitochondria. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. Federal government websites often end in .gov or .mil. 1 - 5 The sudden death of a young athlete is always tragic for the family and community. Trimethoprimsulfamethoxazole and risk of sudden death among patients taking spironolactone. lung failure causing loss of breath. All told, folate is integral for healthy cell function and proliferation, mitochondrial respiration and epigenetic regulation. There are also limitations to this trial that prevent a definitive answer to what we are supposed to do clinically. Their findings provide important messages to caregivers and patients alike. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. The thickening makes it hard for the heart to pump blood and can cause fast heartbeats. The bradycardia, chaotic heart rhythm and blood pressure changes were the most acutely dangerous for this individual, particularly if this was accompanied by disrupted sodium and potassium balance, as we can suspect was the case. Ciprofloxacin (adjusted OR 1.55, 95% CI 1.02-2.38) and nitrofurantoin (adjusted OR 1.70, 95% CI 1.03-2.79) were also associated with an increased risk of sudden death, although the risk with nitrofurantoin was not apparent in a sensitivity analysis. I just finished a five day course of 800mg bactrim DS for a uti. If the goal of the computer is to capture every possible piece of billable data and alert us to every possible bad thing that could happen, the machine becomes part of the patient safety problem. Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. They get warnings like that dozens of times a day. [Free open access link]Antoniou T, et al. Nitrofurantoin was associated with a lower risk of sudden death for the seven day analysis, but not the 14 day analysis. 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. 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. We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Most of the patients who died were. This is a crazy world where one plus one equals three, where down may very well be up and surely pigs have wings. For example, the cases and controls were very different (the cases were more likely to have heart failure, renal failure, and all together more co-morbidities). Doing such an analysis may have further strengthened the argument that hyperkalemia underlies our main observations. "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. Hosted by Eric Widera and Alex Smith. In fact, mixing medicines is very much like playing Russian roulette. Case reports have also confirmed life-threatening high potassium levels with the combination. 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. Briefly, Keflex can cause a deficiency in leucine, an amino acid that regulates something called the mTOR receptor, which, when blocked or, in this case, absent its cognate ligand, would downregulate mTOR and deregulate mitochondrial function. 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. However, many medical professionals are not aware of this effect of trimethoprim, Antoniou adds. 2015 HealthDay. Ciprofloxacin was also associated with an increased risk of sudden death, although this dissipated in the 14 day analysis. Podcast Addict Using the same data, they found that of the 11,968 patients who died of sudden death while receiving potassium-elevating spironolactone, 328 died within 14 days of exposure to certain antibiotics: trimethoprimsulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin. Overcast Getting the dabigatran (Pradaxa) story right Correcting four common mistakes. NHSBA, 2009. The trouble is, physicians and pharmacists often ignore and override drug interaction alerts, especially those they deem relatively unimportant. Antibiotic use and risk of sudden death within 14 days. Like many human infections, UTIs are usually caused . 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Clinical trials, case reports, and laboratory studies show that co-trimoxazole induced hyperkalemia can occur quickly and can cause life threatening arrhythmias, especially among patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers.13 15 16 19 33 34 Our previous research on this drug interaction showed a nearly sevenfold increased risk of hospital admission with hyperkalemia following co-trimoxazole treatment but no such risk with the same alternative antibiotics studied here.14 In the analysis presented here, we found no increased risk of sudden death with nitrofurantoin or norfloxacin. Both spironolactone and trimethoprim-sulfamethoxazole are individually known to increase blood potassium levels, according to the U.S. National Institutes of Health. 1950) self-taught practitioners of geriatric medicine. 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. Your email address will not be published. The researchers caution that limitations to this trial prevent a definitive answer. [2] Antoniou T, Gomes T, Mamdani M et al. 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. We do not capture any email address. When clinically appropriate, alternative antibiotics should be considered in these patients. 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. Of these, 11 968 people died suddenly and 328 of these died. MF drafted the manuscript, which was critically revised for important intellectual content by all authors. Its a good post about another antibiotic to avoid and I appreciate the warning. We have been alarmed about incompatible drug combinations for more than 40 years. Most of the patients who died were over age 85. doi: 10.1136/bmj.g6196. These really should come as no surprise, but again and again they do. 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). This inhibits the reduction of folate into cofactors necessary for DNA synthesis. 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. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics, GeriPal reports. This medication is a combination of two antibiotics: sulfamethoxazole and trimethoprim. MeSH The bacteria won. In other words, an awful lot of people are vulnerable to this potentially deadly drug combination. Sorry for going off on my tangent about FQs. Mr. Zekowski is always on top of his game. FDA Approves Rizatriptan Benzoate Oral Film to Treat Acute Migraine, Pharmacy Focus - Global Vaccination Rates, Study Suggests C. Difficile May Be a Foodborne Illness, Public Health Matters - Harm Reduction, SUD Treatment, Study: COVID-19 Infection Spreads Through Households Via Common Surfaces, Hands, Overcoming Our Blind Spots: Pharmacists Can Help Address Human Trafficking. Accessibility Compared with amoxicillin, trimethoprim- sulfamethoxazole was associated with a more than twofold increase in the risk of sudden Now consider older patients with lifestyle diseases, such as obesity, heart failure, diabetes and high blood pressure, conditions that impair organ function. However, this applies equally to all the antibiotics we studied. Why was its actions on folate metabolism not considered problematic? technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. This material may not be published, broadcast, rewritten, or redistributed. 2014 Oct 30;349:g6196. 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. Think about tradeoffs. Unlike many health sites, we dont force you to purchase a subscription. Previous research had shown that the combination of spironolactone and trimethoprim-sulfamethoxazole caused a 12-fold increased risk of being hospitalized due to high potassium levels compared to use of the heart medicine with another antibiotic, amoxicillin, Antoniou said. 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. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later. CastBox Thanks for a great post, and for helping me to feel less like a dinosaur. Moreover, absent nutrient repletion post antibiotic usage, it is entirely likely that the mitochondrial ill-effects imposed by this drug would become longstanding. But thats the thing about drugs: they dont do just one thing. The large study, conducted over a 17-year period, involved 206 319 patients aged 66 years or older who were treated with spironolactone. 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. Youtube The case story that compelled my investigation into Bactrim included clear symptoms of both wet and dry beriberi, marked by serious dysautonomic function. It is one of those antibiotics, that because it has been around for so long, is considered safe and benign. Audio & Video Editing by Tim Stck of Aspire Digital Productions, Copyright 2023 - GeriPal - All Rights Reserved, Sudden death with trimethoprim-sulfamethoxazole while on ACE-inhibitor or ARBs, large nested case-control study published in the BMJ, The importance of social connection: Julianne Holt-Lunstad, Thomas Cudjoe, & Carla Perissinotto, RCT of Chaplaincy: Lexy Torke, Karen Steinhauser, LaVera Crawley, Storytelling in Medicine: A Podcast with Liz Salmi, Anne Kelly, and Preeti Malani, Psychedelics reasons for caution: Stacy Fischer, Brian Anderson, Theora Cimino. Assumed to be of natural causes such as lisinopril or valsartan can cause heartbeats! Patients taking spironolactone Ontario who were treated with an increased risk of sudden,... Lot of people are vulnerable to this trial prevent a definitive answer to what are. Like playing Russian roulette function and proliferation, mitochondrial respiration and epigenetic regulation and surely pigs have wings this... 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