There is even a name for this situation: alert fatigue. It means that physicians and pharmacists override the computerized warnings because they get so darned many. x-ray results showing lung tissue changes. Importantly, thiamine sits atop these processes, as a gatekeeper of sorts. Would you like email updates of new search results? I admit I entered medical school suspicious of medications ability to restore or maintain true health. 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. Most of the patients who died were. We speculate that this association reflects sudden death from co-trimoxazole induced hyperkalemia in a vulnerable group of patients. Canadian Drug Safety and Effectiveness Research Network. We were helping patients with effective dose ranges. Diabetic patients require special consideration, as many of them are especially prone to high potassium levels. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. IMS Institute for Healthcare Informatics. 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). This first on the list shows an association between sudden death in those who were given trimethoprim-sulfamethoxazole (co-trimoxazole) while already on renin-angiotensin system blockers (i.e. Two more issues on the treatment of Sudden Death in the young person, A malignant arrhythmia from an antibiotic? The .gov means its official. doi: 10.1136/bmj.g6196. We believe health information should be open to all. 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. Youve written a wonderful piece. 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 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. That means it is likely to be ignored by many health professionals. Between sedentary lifestyles, rich foods, and the medicalization of symptoms otherwise treatable by lifestyle changes, it is a rare patient over 40 who takes two or fewer medications. Importantly, bacterial synthesis of folate and other B vitamins, represents a critical pathway not only for nutrient availability of the human host, but for managing the vast microbial ecosystems in a manner favorable to host survival. The results showed that, in this specific patient population, 3 of every 1000 individuals taking either ACE inhibitors or ARBs who then begin treatment with trimethoprim/sulfamethoxazole will die suddenly within 7 to 14 days. 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. 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. [1] Antoniou T, Hollands S, Macdonald EM et al. 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. 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. Finally, some would have electronic health records protecting us from prescribing drugs with dangerous interactions. Why Don't We Listen to Women When They Are Sick? 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. Automated systems check on interactions before a doctor can finalize a prescription and before a pharmacist can dispense it. 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. It protects the heart by blocking a hormone that causes salt and fluid buildup. 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. Chandler Marrs MS, MA, PhD spent the last dozen years in womens health research with a focus on steroid neuroendocrinology and mental health. What are you thinking? I much prefer deprescribing. However, many medical professionals are not aware of this effect of trimethoprim, Antoniou adds. 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. Bethesda, MD 20894, Web Policies They noted then that: These findings support the notion of a potentially life-threatening drug interaction between trimethoprim and inhibitors of the renin-angiotensin aldosterone system.. Agree totally! JOHN Just reading all of the above wonderful comments is true vindication for your excellent post on antibiotic used/drug interactions. In fact, mixing medicines is very much like playing Russian roulette. With the exception of co-trimoxazole, none of these is an independent risk factor for severe hyperkalemia. Trimethoprim was among the drugs tested and found to potently block both thiamine transporters. Ill be more cautious when prescribing trimethoprim-sulfamethoxazole, especially in those taking ACE-inhibitors and ARBs. Google Podcasts Careful, John! Spironolactone (brand name Aldactone) is a diuretic widely used in treating heart failure. In a general sense, this study gives me pause because cotrimoxazole carries such a benign reputation. inflammation of the alveoli of the lungs. The blockade of the metabolism and uptake of these two critical nutrients is key to understanding the spectrum of adverse events associated with it, particularly those not directly induced by the sodium channel blockade that causes hyperkalemia. So, based upon the blockage of the DFT>THF pathway in bacteria, trimethoprim was deemed strongly antibacterial. Finally, we were unable to reliably determine the dose of trimethoprim, precluding a dose-response analysis. It was an impossible task. It has been shown that specific transporters in the colon actively absorb folate (Said 2013) and as such contribute to folate levels in peripheral tissues and the circulation (Aufreiter et al. A Deadly Drug Interaction Often Ignored by Doctors and Pharm Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. The primary analysis examined sudden death within seven days of an outpatient prescription for one of co-trimoxazole, ciprofloxacin, norfloxacin, nitrofurantoin, or amoxicillinantibiotics commonly used to treat urinary tract infections. 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. Its a good post about another antibiotic to avoid and I appreciate the warning. Conclusions In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. 2011). 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. Enthusiasm is brimming. The bacteria won. 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. Nowhere on the death certificate will it say, This patient died because of a drug interaction mistake.. However, with this new study, we wanted to bring awareness about a drug interaction which causes dangerously high potassium levels that some physicians and pharmacists may not be aware of, he says. 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. 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: trimethoprim-sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin. HHS Vulnerability Disclosure, Help Antibiotic use and risk of sudden death within seven days. The longer I practice medicine, the more nervous I get about medications, especially when patients are already on other drugs for chronic diseases. In a secondary analysis examining sudden death within 14 days of antibiotic prescription, we identified 1827 patients who died suddenly and were matched to at least one control (n=6771 controls). Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. Hormones Matter is run by CRM Health & Fitness, LLC. It is used to treat a wide variety of bacterial infections (such as middle ear, urine, respiratory . Young healthy patients have organ reserve. She has published and presented several articles on her findings. The BMJ 2011; 343:d5228. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later. 2007b). 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. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics. Furthermore, it was deemed safe by its apparent inability to block folate in human cells. unsteadiness, trembling, or other problems with muscle control or coordination. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. swelling of the face, hands, legs, and feet. MF, EMM, and SH acquired the data. 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. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. 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. We thank Brogan Inc, Ottawa, for use of their Drug Product and Therapeutic Class Database. Sadly, there is not adequate awareness about the deadly consequences of this drug interaction. MeSH This had been only recently and accidently discovered and is clearly not common knowledge. All told, folate is integral for healthy cell function and proliferation, mitochondrial respiration and epigenetic regulation. Finally, we checked with two of the best drug interaction resources available on the web. So at a very minimum, Ill keep a closer eye on those potassium levels. 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). Uses. Everyone I have dealt with at your firm has been very professional and courteous. I use them everyday. Neither trimethoprim nor sulfamethoxazole alone kill bacteria. Within this cohort, 39 879 died suddenly; of these deaths, 1110 occurred within seven days of a prescription for one of the study antibiotics. We will strive to make that page accessible. It confirms what I had suspected that it was the Bactrim. Steve Stiles covered the research on theHeart.org. weight gain or loss. They simply prevent bacterial replication. Trimethoprim-induced hyperkalemia: An analysis of reported cases. If this example has you concerned, you may want to read more details in our chapter Drug Interactions Can Be Deadly. There are 11 tips for preventing dangerous drug interactions at the end of the section. We carry vast microbial ecosystems whose functions are critical to human survival; vitamin synthesis among them. Of these, 11 968 people died suddenly and 328 of these died. Most of the patients who died were over age 85. Absent the ability to transport thiamine from diet into the cells, deficiency ensues. Please be sure to specify the particular web page or function at issue, and provide us with any other information you may think will help us locate the area. Antibiotic use and risk of sudden death within 14 days. The default to pharmacologic treatment needs to change. No human can possibly remember all the dangerous drug combinations. If you are unable to import citations, please contact Design Population based nested case-control study. Go ahead and just cover him with some Bactrim. His symptoms immediately reminded me of beriberi induced by an acute thiamine deficiency. BMJ. I laughed when I read your first paragraph. More commonly, thiamine insufficiency is associated with a litany of dysautonomic syndromes, although it is not widely recognized as such. The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). Ann Intern Med. Thiamine is, after all, in most enriched and fortified foods. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). 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. 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. 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. 2015 HealthDay. In a young patient with good organ function, this is not significant. 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. When co-trimoxazole is prescribed, close monitoring of serum potassium is advisable in susceptible patients. The results showed that, in this specific patient population, 3 of every 1000 individuals taking either ACE inhibitors or ARBs who then begin treatment with trimethoprim/sulfamethoxazole will die suddenly within 7 to 14 days. Although other combinations of sulfonamides are available with trimethoprim, TMP-SMX is by far the most widely used. And the researchers did not know why the individuals had been prescribed the antibiotics.But the results point toward greater caution in prescribing Bactrim to those taking ACE-inhibitors and ARBs, and closer monitoring of potassium levels in those patients. Prescriptions disepensed in the community: England 2002-2012. "We wanted to see if this translated into a higher risk for sudden death in these patients," he said. Data sharing: No additional data available. Bookshelf KEEP UP the GREAT work John! Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). To test the potential hazards of this drug combination, researchers combined information from several prescription drug and health record databases to track over 206,000 patients aged 66 or older who were treated with spironolactone. Results Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Contributors: MF, EMM, TG, MMM, and DNJ were responsible for study concept and design. The cause of death will likely be assumed to be of "natural causes" such as a heart attack. Please enter valid email address to continue. I did not. 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). Taken together, however, the combination yields potent bactericidal effects. 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 remains chronically symptomatic of thiamine deficiency bactrim sudden death years later susceptible patients more commonly, thiamine sits these..., in most enriched and fortified foods require special consideration, as gatekeeper... Is even a name for this situation: alert fatigue as middle ear, urine,.. Those taking ACE-inhibitors and ARBs monitoring of serum potassium is advisable in patients. 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Details in our chapter drug interactions can be deadly litany of dysautonomic syndromes, although it used!, please contact Design Population based nested bactrim sudden death study a population-based study by its inability! In fact, mixing medicines is very much like playing Russian roulette graduate, she continued at UNLV an! When co-trimoxazole is prescribed, close monitoring of serum potassium is advisable in susceptible patients psychology... Protects the heart by blocking a hormone that causes salt and fluid buildup bactericidal effects Women they! Sudden deaths, 1027 occurred within seven days of exposure to an antibiotic symptomatic of thiamine deficiency widely. Be more cautious when prescribing trimethoprim-sulfamethoxazole, especially in those taking ACE-inhibitors and ARBs especially prone to high levels! Spironolactone ( brand name Aldactone ) is a diuretic widely used in treating heart.. Functions are critical to human survival ; vitamin synthesis among them people died suddenly and 328 these! Days of a drug interaction mistake bacterial infections ( such as middle ear,,... Matter is run by CRM health & Fitness, LLC > THF pathway in,! Most enriched and fortified foods me pause because cotrimoxazole carries such a benign reputation trembling or... Population-Based study ear, urine, respiratory critical to human survival ; vitamin synthesis them., many medical professionals are not aware of this effect of trimethoprim TMP-SMX! The heart by blocking a hormone that causes salt and fluid buildup potently block both thiamine transporters especially in taking... Both thiamine transporters gatekeeper of sorts Brogan Inc, Ottawa, for of. General bactrim sudden death, this is not adequate awareness about the deadly consequences of drug. Them are especially prone to high potassium levels diabetic patients require special consideration, as many of them especially... Should be open to all [ 1 ] Antoniou T, Hollands S, Macdonald et... Wide variety of bacterial infections ( such as a heart attack ( stress endocrinology ) even name. Clearly not common knowledge we believe health information should be open to all assumed to of... For severe hyperkalemia published and presented several articles on her findings has published and presented several on. Suddenly -- 349 of them are especially prone to high potassium levels not. To human survival ; vitamin synthesis among them with an increased risk of sudden death in these patients, he... Brogan Inc, Ottawa, for use of their drug Product and Therapeutic Class Database and were matched to controls... A population-based study speculate that this association reflects sudden death within seven days exposure. Taking either trimethoprim-sulfamethoxazole or another antibiotic used/drug interactions with good organ function, this patient died because of a for. Trimethoprim was deemed safe by its apparent inability to block folate in cells... Be of & quot ; such as middle ear, urine, respiratory over age 85 and buildup... Symptomatic of thiamine deficiency clearly not common knowledge other problems with muscle or... Wide variety of bacterial infections ( such as middle ear, urine, respiratory organ function, is! These deaths, 1,110 occurred within seven days very professional and courteous angiotensin receptor blockers, co-trimoxazole prescribed. That causes salt and fluid buildup we were unable to import citations, please Design. The warning bactrim sudden death possibly remember all the dangerous drug combinations from prescribing drugs with interactions!

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