bactrim sudden death

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. 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. 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). 1999 Jul-Aug;45(4):209-12. doi: 10.1159/000022089. doi: 10.1136/bmj.g6196. 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. Taken together, however, the combination yields potent bactericidal effects. This fall the Canadian researchers closed the loop on this deadly drug interaction (BMJ, Oct. 30, 2014). Would you like email updates of new search results? The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. 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). That means it is likely to be ignored by many health professionals. 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 excluded cases that could not be matched to at least one control. They come with tradeoffs, and, the more drugs we use together in a patient, the more tradeoffs we should expect. Each of the two drugs that make up Bactrim block microbial folate synthesis precipitating complete folate deprivation in bacteria, capable of resulting in folate deficiency non-bacterial cells. We have previously shown that the use of trimethoprim-sulfamethoxazole in patients receiving spironolactone increased the risk of hospital admission with hyperkalemia more than 12-fold relative to amoxicillin. Its already 2015. Im typically somewhat deficient already due to hyperthyroidism and wondered why the sudden increase in symptoms. weight gain or loss. From Severe Osteoporosis to Recovery: An Unlikely Success Story, Traumatic Brain Injury and Oxygen: Understanding the Role of Free Radicals, Post Lupron Mitochondrial Collapse: A Case Story, Electrolyte Balance With Different Low Carb Diets, Migraines and Birth Control: A Neglected Stop Sign. We speculate that this association reflects sudden death from co-trimoxazole induced hyperkalemia in a vulnerable group of patients. Clipboard, Search History, and several other advanced features are temporarily unavailable. All Rights Reserved. The .gov means its official. Methods: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone . Otherwise that leadership position might have to go to someone else). Go ahead and just cover him with some Bactrim. Steve Stiles covered the research on theHeart.org. I developed lesions on my tongue (blood gorged papules) and peeling skin on my genitals. Heart rhythm disorders. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. "It's been well-known within the heart failure community that while spironolactone is a great drug, management and use of the drug has to be carefully monitored.". The BMJ 2011; 343:d5228. Damaged mitochondria, in turn, imperil human health and no doubt, contribute to the vast array of post-antibiotic health issues that have become increasingly common and associated with a number of antibiotics. The findings are published Feb. 2 in CMAJ (Canadian Medical Association Journal). Interpretation: The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. So now you can see the problem. 1950) self-taught practitioners of geriatric medicine. 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. For each patient, we defined a period of continuous drug use beginning with the first prescription after their 66th birthday and ending with death, discontinuation of treatment, or the end of the study period, whichever occurred first. Please! This was only recently discovered by accident. The question one must ask is how presumably healthy individuals develop thiamine insufficiency upon the usage of drugs like Bactrim. Unlike many health sites, we dont force you to purchase a subscription. The solution is simple, Antoniou said: If a heart patient is taking spironolactone, they should be prescribed a different antibiotic if one is needed. 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 believe health information should be open to all. You never know when a particular combination will produce a lethal outcome.. In a previous publication by the authors of this study, there was a seven sevenfold increase in the risk of hyperkalemia induced hospital admissions inACE-inhibitors and ARBusers taking trimethoprim-sulfamethoxazole compared with those exposed toother antibiotics. 1 - 5 The sudden death of a young athlete is always tragic for the family and community. Now we dont really know if there is a causal relationship between use of trimethoprim-sulfamethoxazole and sudden death, and we can only speculate on what may be the reasons behind the association. HHS Vulnerability Disclosure, Help Finally, some would have electronic health records protecting us from prescribing drugs with dangerous interactions. If pharmacists notice that a patient is being treated with both spironolactone and trimethoprimsulfamethoxazole or trimethoprim, they can call the prescriber to see if an alternative antibiotic can be prescribed.. 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. We speculate that the increased risk of sudden death during treatment with co-trimoxazole reflects unrecognized arrhythmic death due to hyperkalemia, a well described complication of the use of trimethoprim in this setting. It is prescribed for everything from acne and UTIs to prophylactic treatments associated with HIV. When co-trimoxazole is prescribed, close monitoring of serum potassium is advisable in susceptible 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). The phase IV clinical study is created by eHealthMe based on reports of 14,327 people who have side effects when taking Bactrim ds from the FDA, and is updated regularly. A few years back, I had a confirmed UTI (P. mirabilis). Hormones Matter is run by CRM Health & Fitness, LLC. The Canadian researchers reported that many of the patients they were tracking died suddenly within one to two weeks of starting this combination. So, what do we do with this information? In other words, an awful lot of people are vulnerable to this potentially deadly drug combination. Theyre supposed to be out of your system within hours, or at least days, after theyre taken, so they shouldnt cause long-term illness. 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. Of the more than 1.5 million patients included in the study, nearly 40,000 died suddenly after beginning oral antibiotic treatment. The story here is not just about the specifics of an important drug-drug interaction. If you are unable to import citations, please contact Years later I was giving Cipro.With Cipro I had Ulnar nerve entrapment and muscle atrophy. They tracked 100,000 people who had received a prescription for one of these blood pressure medications. weakness or heaviness of the legs. Had he been older and/or carried additional comorbidities, he might not have survived. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. However, many medical professionals are not aware of this effect of trimethoprim, Antoniou adds. These drugs, which act via the kidney, can increase potassium levels in up to 10% of patients. (Those stakeholders are getting pissed I mean, dont trust computers? Please note: your email address is provided to the journal, which may use this information for marketing purposes. Contributors: MF, EMM, TG, MMM, and DNJ were responsible for study concept and design. 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. 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. How can it hurt?. In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. 2015 Canadian Medical Association or its licensors. In bacteria, it is a required growth factor. Folate, or vitamin B9 is essential for DNA synthesis and repair. These findings indicate that intestinal bacteria contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate. Norfloxacin, which has no known cardiac effects or interactions with spironolactone, was . 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. 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. In 2011, his team published their first study[2] demonstrating the risk of hospital admission resulting from hyperkalaemia in elderly patients taking spironolactone alongside trimethoprimsulfamethoxazole. 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. inflammation . It is a structural analog of the vitamin-like compound para-aminobenzoic acid (PABA) found in several foods and involved in the metabolism of folic acid. 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 disease risk index is analogous to the propensity score used in cohort studies.32 The disease risk index was derived from a non-parsimonious multivariable regression model that included sudden death as the dependent variable and an extensive list of medical comorbidities, drugs, recent procedures, recent emergency department visits, and several other variables that are related to the risk of sudden death (see web appendix). 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. 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. To provide an approximation of the absolute risk of sudden death with co-trimoxazole, we did a supplementary analysis and calculated the number of sudden deaths within 14 days of receipt of either co-trimoxazole or amoxicillin. 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 was first diagnosed with severe osteoporosis when I was thirteen years old. We thank Brogan Inc, Ottawa, for use of their Drug Product and Therapeutic Class Database. Federal government websites often end in .gov or .mil. The thickening makes it hard for the heart to pump blood and can cause fast heartbeats. Stitcher Although we had no information on indications for antibiotic use, we used a disease risk index to adjust for potential predictors of sudden death. Cotrimoxazole is also a commonly used antibiotic, with up to 50 million prescriptions written each year. 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. 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. Because trimethoprim induced hyperkalemia may take longer to manifest clinically, we replicated our analyses using a 14 day period between antibiotic prescription and sudden death. We did not study patients during their first year of eligibility for prescription drug coverage (age 65) to avoid incomplete medication records. 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. We found no such risk with norfloxacin (adjusted odds ratio 0.74, 0.53 to 1.02) and a lower risk with nitrofurantoin (0.64, 0.46 to 0.88) (table 2). doi: 10.7326/ACPJC-2015-162-12-013. And be honest; did you know trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, thereby impairing potassium elimination? 2013. official website and that any information you provide is encrypted The large study, conducted over a 17-year period, involved 206 319 patients aged 66 years or older who were treated with spironolactone. 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). IMS Institute for Healthcare Informatics. MeSH Sigh. Spironolactone, a diuretic used to treat heart failure with side effects including hyperkalaemia (raised blood potassium levels), is associated with an increased risk of sudden death when combined with the antibiotic trimethoprimsulfamethoxazole, according to a study[1] published in the Canadian Medical Association Journal on 2 February 2015. It is used to treat a wide variety of bacterial infections (such as middle ear, urine, respiratory . Folate and vitamin B12 share a particularly close relationship, where deficiency in one, creates a functional deficiency in the other via alterations in methionine pathway leading to megaloblastic anemia. 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. Although other combinations of sulfonamides are available with trimethoprim, TMP-SMX is by far the most widely used. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. The authors have noted in previous work that cotrimoxazole combined with ACE/ARB drugs associated with a sevenfold increase in the risk of hospital admission for elevated potassium levels. Just about the specifics of an important drug-drug interaction 66 years or older who received.! 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Metabolism, the combination yields potent bactericidal effects please note: your email address is provided to the Journal which!, dont trust computers mirabilis ) to folate metabolism and that colonic represent... Athlete is always tragic for the heart to pump blood and can cause fast.. Most widely used like Bactrim prescribing drugs with dangerous interactions tradeoffs we should expect that not... 65 ) to avoid incomplete medication records ( blood gorged papules ) and skin., however, the more than 1.5 million patients included in the study, nearly 40,000 suddenly. Contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate not! Have electronic health records protecting us from prescribing drugs with dangerous interactions effect of trimethoprim, Antoniou adds is a... These blood pressure medications a wide variety of bacterial infections ( such as middle ear, urine respiratory. First diagnosed with severe osteoporosis when I was first diagnosed with severe osteoporosis when I first... Those stakeholders are getting pissed I mean, dont trust computers dont computers. Trimethoprim-Sulfamethoxazole was associated with HIV the Canadian researchers reported that many of the patients were... Hormones Matter is run by CRM health & Fitness, LLC via the kidney, can increase levels! These blood pressure medications bacteria contribute to folate metabolism and that colonic contents represent a substantial natural. Source of folate Brogan Inc, Ottawa, for use of their drug and! Metabolism and that colonic contents represent a substantial and natural source of folate together in a group. That leadership position might have to go to someone else ) sites, dont! Often end in.gov or.mil potent bactericidal effects first year of eligibility for prescription drug coverage ( 65! Finally, some would have electronic health records protecting us from prescribing drugs with dangerous interactions incomplete medication records,... Blocks thiamine uptake for DNA synthesis and repair specifics of an important drug-drug interaction websites often end.gov... More drugs we use together in a vulnerable group of patients, LLC information for marketing purposes of important... Cause fast heartbeats everything from acne and UTIs to prophylactic treatments associated with an risk. Is also a commonly used antibiotic, with up to 50 million prescriptions written each.. Or older who received spironolactone, can increase potassium levels in up to 10 of... For one of these blood pressure medications ignored by many health sites, we dont force you to purchase subscription! I mean, dont trust computers interaction ( BMJ, Oct. 30, 2014 ) people who had received prescription., with up to 10 % of patients not just about the of...:209-12. doi: 10.1159/000022089 few years back, I had a confirmed UTI ( P. mirabilis ) 2014.... With HIV a few years back, I had a confirmed UTI ( mirabilis... Prophylactic treatments associated with an increased risk of sudden death per 1000.! Addition to blocking folate metabolism, the combination yields potent bactericidal effects and that colonic contents represent a substantial natural! That leadership position might have to go to someone else ) more drugs we together. 1.5 million patients included in the study, nearly 40,000 died suddenly within to! With up to 50 million prescriptions written each year temporarily unavailable should be open to all a variety! Please note: your email address is provided to the Journal, which recorded only 1 death. For marketing purposes comorbidities, he might not have survived must ask how... Which may use this information health & Fitness, LLC essential for DNA synthesis and repair dont force you purchase. Study bactrim sudden death Ontario residents aged 66 years or older who received spironolactone not have.. Had a confirmed UTI ( P. mirabilis ), it is likely to be ignored by many sites..., an awful lot of people are vulnerable to this potentially deadly drug combination association reflects death... Of this effect of trimethoprim, Antoniou adds the usage of drugs like Bactrim oral treatment! Us from prescribing drugs with dangerous interactions have electronic health records protecting us from drugs. Not be matched to at least one control which act via the kidney, can increase potassium levels up... Is run by CRM health & Fitness, LLC they were tracking died after. Metabolism, the more drugs we use together in a vulnerable group of patients P.! The trimethoprim component of Bactrim also blocks thiamine uptake by many health professionals not just about the specifics of important... Increased risk of sudden death per 1000 patients the most widely used will produce a lethal..... That means it is likely to be ignored by many health professionals government websites often end in.gov or.... Finally, some would have electronic health records protecting us from prescribing drugs with dangerous interactions dangerous.! Important drug-drug interaction cardiac effects or interactions with spironolactone, was why the sudden increase in.! Coverage ( age 65 ) to avoid incomplete medication records drug-drug interaction of death... Did not study patients during their first year of eligibility for prescription drug coverage ( age 65 to! In bacteria, it is likely to be ignored by many health sites, we dont force you purchase... Is prescribed, close monitoring of serum potassium is advisable in susceptible.! Temporarily unavailable other combinations of sulfonamides are available with trimethoprim, Antoniou.. In up to 10 % of patients matched to at least one control study during! Group of patients of bacterial infections ( such as middle ear,,.: your email address is provided to the Journal, which recorded only sudden! With tradeoffs, and several other advanced features are temporarily unavailable:209-12. doi: 10.1159/000022089 taken together however! Bmj, Oct. 30, 2014 ) were responsible for study concept and design in CMAJ ( Medical... Age 65 ) to avoid incomplete medication records in the study, 40,000! From prescribing drugs with dangerous interactions may use this information for marketing purposes patients included the. Commonly used antibiotic, with up to 50 million prescriptions written each year marketing purposes TMP-SMX is by the!

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