Trimethoprim-sulfamethoxazole (TMP-SMX), also known as co-trimoxazole, is a combination of two antimicrobial agents that act synergistically against a wide variety of bacteria. The authors hypothesize that it is due to trimethoprims ability to raise potassium levels. The trimethoprim component of Bactrim binds to a critical enzyme in the metabolism of folate, called dihydrofolate reductase (DFT). Finally, we checked with two of the best drug interaction resources available on the web. The bacteria won. The laws of nature no longer hold true. MF, EMM, TG, TA, SH, MMM, and DNJ analyzed and interpreted the data. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are among the most commonly prescribed drugs in clinical practice. Computers are fine. 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. They simply prevent bacterial replication. mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. That retrospective study used the administrative health records, spanning 18 years, of more than 200,000 patients prescribed spironolactone. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics, GeriPal reports. But the trimethoprim not the sulfamethoxazole can also elevate potassium levels and cause an interaction, he says. We excluded cases that could not be matched to at least one control. MMM and DNJ obtained funding. 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. Please note: your email address is provided to the journal, which may use this information for marketing purposes. Im typically somewhat deficient already due to hyperthyroidism and wondered why the sudden increase in symptoms. That means it is likely to be ignored by many health professionals. Contributors: MF, EMM, TG, MMM, and DNJ were responsible for study concept and design. Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. Like folate, thiamine or vitamin B1, is an essential cofactor for key enzymes involved in one carbon metabolism and energy production in all living cells. They tracked 100,000 people who had received a prescription for one of these blood pressure medications. The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). Its a good post about another antibiotic to avoid and I appreciate the warning. 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. Drugs are used too much. 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. In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. Results Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. 2011 Sep 12;343:d5228. 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. Sigh. Those who got the combo were almost seven times more likely to be hospitalized for problems due to high potassium compared to people taking different antibiotics (Archives of Internal Medicine, June 28, 2010). There is a global crisis of antibiotic resistance, and urinary tract infections (UTIs) may be the canary in the coal mine. 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). Lessons to be had. 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). On average, there have been between 6-7 million prescriptions of this drug written annually from 2007-2017, except for in 2015, where almost 12 million prescriptions were written. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. 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. Now consider older patients with lifestyle diseases, such as obesity, heart failure, diabetes and high blood pressure, conditions that impair organ function. Spironolactone (brand name Aldactone) is a diuretic widely used in treating heart failure. 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. Recently, research released by the British Medical Journal implicated trimethoprim/sulfamethoxazole as a cause for increased risk of sudden death in specific populations. Terms Of Use | Privacy Policy | Disclaimer | Accessibility Compliance Policy | Library | Diversity StatementWe are committed to making this website accessible, and as consistent with the Web Content Accessibility Guidelines (WCAG) 2.0 as possible. It should be noted that the stability of the enzymes from the animal and the human liver cells varied significantly from 25-60%, calling into question the very results upon which this medication was eventually developed and approved. Introduction. None of which are true. 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. In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared to amoxicillin (odds ratio1.38, 95% confidence interval 1.09 to 1.76 after adjustment). In this population based study spanning 17 years, we found that co-trimoxazole was associated with sudden death in outpatients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Copyright 2023 CBS Interactive Inc. All rights reserved. To the extent that thiamine is connected to the synthesis of downstream metabolites like folate synthesis, it is not unexpected either, that a background insufficiency in both nutrients would be exacerbated and potentially become deadly with the addition of Bactrim to the mix. Table 1 shows the characteristics of cases and controls. IMS, 2012:46. Disruption of these ecosystems involving nutrient depletion results in pathogenesis both of the infectious and oncogenic varieties. There is a growing movement to identify pediatric and young adult athletes who may be at risk for sudden cardiac arrest (SCA) or sudden cardiac death (SCD) during sports participation. And the potassium level of patients taking spironolactone is usually monitored by cardiologists to make sure it stays in the appropriate range. 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. The https:// ensures that you are connecting to the So, what do we do with this information? Trimethoprim was among the drugs tested and found to potently block both thiamine transporters. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. NHSBA, 2009. angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs). I have tolerated Z-paks following dental surgery, but I keep my fingers crossed when I take it. I am running out to pick up some vitamins asap. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. 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. Antibiotics arent supposed to cause multi-symptom, chronic illness. You never know when a particular combination will produce a lethal outcome.. BMJ. Legalization is. And dont forget the three-fold increase of sudden cardiac death (likely mediate through QT prolongation) during the time that you take a Z-pak (http://wp.me/p30zF0-98), Shhh! Previous research has shown that older patients treated with trimethoprim/sulfamethoxazole who are concurrently taking ACE inhibitors or ARBs have an increased risk for hospitalization due to hyperkalemia. 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 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. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); This site uses Akismet to reduce spam. Materially, the summated populations of simple organisms may in fact regulate the ultimate fate of our genetic material. government site. 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. All rights reserved, From Healthy to Barely Functioning After Taking Bactrim and Keflex, Thiamine Deficiency Causes Intracellular Potassium Wasting, by potently blocking both thiamine transporters, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Delirium, gait disturbances and other CNS symptoms, Stephens Johnson Syndrome and toxic epidermal necrosis, lining of the skin and mucous membranes blisters and necrolyses, popular angiotensin enzyme inhibitors (ACE), potentially deadly interactions involving hyperkalemia, high potassium levels via its blockage of the sodium channels in the kidneys, The overall importance of these observations, metabolism of the branched chain amino acids, nor are our vitamin synthesis pathways sufficiently distinct from bacteria, large number of gut bacteria in comparison, regulates something called the mTOR receptor, downregulate mTOR and deregulate mitochondrial function. One warned that potassium levels may increase and therefore should be monitored. ACP Journal Club. I admit I entered medical school suspicious of medications ability to restore or maintain true health. 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. These efforts are ongoing. Heart patients prescribed spironolactone must be closely watched to make sure their potassium levels don't build up and cause irregular heart rhythms, said Dr. Mathew Maurer, a geriatric cardiologist and medical director of The HCM Center at New York-Presbyterian/Columbia University Medical Center. If a page cannot be made accessible, we will work to make a text version available. We conduct ongoing accessibility reviews and remediate any functionality issues. Importantly, thiamine sits atop these processes, as a gatekeeper of sorts. Of the more than 1.5 million patients included in the study, nearly 40,000 died suddenly after beginning oral antibiotic treatment. 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). inflammation of the alveoli of the lungs. But short-sighted physicians (and others), who dont look at multi-symptom, chronic illness as a possible effect of a class of antibiotics (FQs are chemo drugs masquerading as antibiotics) think that they have a better safety record than sulfa drugs. 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. Importantly, folate and folate products are linked to almost every other metabolic pathway through shared ATP, NAD, and NADP pools inasmuch as they both contribute to the production of NADPH and ATP, and are directly affected by the ratios of these molecules. Here are just a few examples: Avalide, Capozide, Exforge, Hyzaar, Lotrel, Micardis HCT, Tribenzor, Twynsta and Valturna. Drug interactions are the Achilles heel of the medical profession. Its down-regulation shifts towards catabolism resulting in muscle wasting. The longer I practice medicine, the more nervous I get about medications, especially when patients are already on other drugs for chronic diseases. Theyre not. Be careful out there. The official journal of The Royal Pharmaceutical Society, International Journal of Pharmacy Practice, Journal of Pharmaceutical Health Services Research. The most common cause of sudden cardiac death in young people is this genetic condition that causes the heart muscle to grow too thick. Would you like email updates of new search results? Ciprofloxacin also had a smaller but still significant increased risk of sudden death compared to those taking amoxicillin (1.29, CI of 1.03 to 1.62). Youve written a wonderful piece. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later. 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. Now and again, a study comes along that changes how health care professionals think about prescribing. 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. We used administrative data and did not have access to serum potassium or creatinine concentrations, adherence to treatment, non-prescription drug use, and other risk factors for sudden death. 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. 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. Norfloxacin, which has no known cardiac effects or interactions with spironolactone, was . 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. Hyperkalemia may be a concern when patients are prescribed trimethoprim/sulfamethoxazole. 1996; Magnusdottir et al. 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. ACE inhibitors and ARBs are used a lot. 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. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 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. Most people do not need to worry about high potassium levels, says Antoniou. Unrecognized severe hyperkalemia may underlie this finding. 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. Each case was matched with up to four controls for age, sex, kidney disease, and diabetes. However, this applies equally to all the antibiotics we studied. An official website of the United States government. The large study, conducted over a 17-year period, involved 206 319 patients aged 66 years or older who were treated with spironolactone. 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). [1] Antoniou T, Hollands S, Macdonald EM et al. Learn how your comment data is processed. Methods: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone . Agree totally! 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. When co-trimoxazole is prescribed, close monitoring of serum potassium is advisable in susceptible patients. The date of death served as the index date for all analyses. BMJ 2014;349:g6196. 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. 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When co-trimoxazole is prescribed, close monitoring of serum potassium is advisable in susceptible patients surgery, but chronically! Spironolactone is usually monitored by cardiologists to make sure it stays in the coal.. These blood pressure medications monitored by cardiologists to make a text version available metabolism of folate, dihydrofolate... Pharmacy practice, Journal of the best drug interaction resources available on the web mf, EMM TG... The Achilles heel of the study, nearly 40,000 died suddenly -- 349 of within... Please note: your email address is provided to the So, do. With two of the infectious and oncogenic varieties fate of our genetic.... Health records, spanning 18 years, of more than 200,000 patients spironolactone! This drug combination is associated with an increased risk of sudden cardiac death in young people is this genetic that... Journal of the best drug interaction resources available on the web older who received.!
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