trimethoprim--sulfamethoxazole-drug-combination and Hyperkalemia

Trimethoprim-sulfamethoxazole (TMP/SMX) causes hyperkalemia, and hyponatremia caused by TMP/SMX is a challenge for clinicians. We described the clinical features of hyponatremia induced by TMP/SMX after collecting cases.. The median age of the 24 patients (10 males and 14 females) was 67 years (range: 28-90 years). Hyponatremia induced by TMP/SMX manifested as nausea (41.7%) and vomiting (29.2%) or asymptomatic hyponatremia (20.8%). The median duration of hyponatremia was 5 days (range: 3-10 days). The median serum sodium concentration was 118 mmol/L (range: 101-128.1 mmol/L). The serum sodium levels gradually returned to the normal range at 4 days (median; range: 2-14 days) after withdrawing TMP/SMX.. TMP/SMX-induced hyponatremia is a rare and serious adverse reaction. Clinicians should be aware of electrolyte disturbances caused by TMP/SMX and should always consider electrolyte monitoring.

Topics: Adult; Aged; Aged, 80 and over; Electrolytes; Female; Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Sodium; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalemia is a common and potentially life-threatening complication following kidney transplantation that can be caused by a composite of factors such as medications, delayed graft function, and possibly potassium intake. Managing hyperkalemia after kidney transplantation is associated with increased morbidity and healthcare costs, and can be a cause of multiple hospital admissions and barriers to patient discharge. Medications used routinely after kidney transplantation are considered the most frequent culprit for post-transplant hyperkalemia in recipients with a well-functioning graft. These include calcineurin inhibitors (CNIs), pneumocystis pneumonia (PCP) prophylactic agents, and antihypertensives (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers). CNIs can cause hyperkalemic renal tubular acidosis. When hyperkalemia develops following transplantation, the potential offending medication may be discontinued, switched to another agent, or dose-reduced. Belatacept and mTOR inhibitors offer an alternative to calcineurin inhibitors in the event of hyperkalemia, however should be prescribed in the appropriate patient. While trimethoprim/sulfamethoxazole (TMP/SMX) remains the gold standard for prevention of PCP, alternative agents (e.g. dapsone, atovaquone) have been studied and can be recommend in place of TMP/SMX. Antihypertensives that act on the Renin-Angiotensin-Aldosterone System are generally avoided early after transplant but may be indicated later in the transplant course for patients with comorbidities. In cases of mild to moderate hyperkalemia, medical management can be used to normalize serum potassium levels and allow the transplant team additional time to evaluate the function of the graft. In the immediate post-operative setting following kidney transplantation, a rapidly rising potassium refractory to medical therapy can be an indication for dialysis. Patiromer and sodium zirconium cyclosilicate (ZS-9) may play an important role in the management of chronic hyperkalemia in kidney transplant patients, although additional long-term studies are necessary to confirm these effects.

Topics: Humans; Hyperkalemia; Kidney Transplantation; Renin-Angiotensin System; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis; Aged; Anti-Infective Agents; Anuria; Arthritis, Rheumatoid; Coma; Emergencies; Humans; Hyperkalemia; Hypoglycemia; Kidney Failure, Chronic; Male; Myocardial Ischemia; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abnormalities, Drug-Induced; Anti-Infective Agents; Anticoagulants; Biomedical Research; Cytochrome P-450 Enzyme System; Drug Eruptions; Drug Interactions; Female; Folic Acid Deficiency; Hematologic Diseases; Hemolysis; Humans; Hyperkalemia; Hypoglycemia; Hypoglycemic Agents; Immunocompromised Host; Infant, Newborn; Infant, Small for Gestational Age; Kidney; Nervous System Diseases; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination; Warfarin

A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell anemia presented to the University of Wisconsin Hospital on two separate occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). Several days into each treatment course he developed hyperkalemia and systemic acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The abnormalities resolved in the first instance with the addition of amphotericin B while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX. While an increasing number of cases with TMP/SMX-induced hyperkalemia have been reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy, occurring in patients with predisposing factors for acidosis such as aldosterone defects, medullary dysfunction and renal insufficiency.

Topics: Acidosis, Renal Tubular; Adult; AIDS-Related Opportunistic Infections; Anemia, Sickle Cell; Anti-Infective Agents; Drug Therapy, Combination; HIV-1; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. A previously unreported and potentially lethal adverse reaction associated with "high dose" trimethoprim-sulfamethoxazole therapy, hyperkalemia, was described. Subsequent to the descriptions of hyperkalemia with "high dose" trimethoprim-sulfamethoxazole, a handful of cases noted the development of hyperkalemia with "standard dose" trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A surveillance study of patients treated with "standard dose" trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium associated with trimethoprim-sulfamethoxazole therapy. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole-induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Hence, trimethoprim-sulfamethoxazole therapy was found to be associated with a new adverse reaction, hyperkalemia, nearly 25 years after its introduction into clinical practice as an antimicrobial agent.

Topics: Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Hyperkalemia; Kidney; Potassium; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Topics: Age Factors; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Dose-Response Relationship, Drug; Humans; Hyperkalemia; Kidney; Pneumonia, Pneumocystis; Potassium; Renal Insufficiency; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.

Topics: Acquired Immunodeficiency Syndrome; Clinical Trials as Topic; Dapsone; Drug Therapy, Combination; Humans; Hyperkalemia; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A prospective, randomized clinical study was undertaken to determine the effect of standard-dose trimethoprim-sulfamethoxazole combination treatment on serum potassium concentrations in outpatients treated in an ambulatory clinic. Ninety-seven patients were treated with oral antibiotics for a variety of infections. Fifty-one patients treated with trimethoprim-sulfamethoxazole (trimethoprim, 320 mg/day; sulfamethoxazole, 1,600 mg/day) constituted the treatment group, while 46 patients treated with other antibiotics served as controls. Serum potassium, sodium, and chloride concentrations, serum carbon dioxide content, blood urea nitrogen level, serum creatinine level, and serum glucose concentration were measured. The baseline serum potassium concentration in the treatment group was 4.30 +/- (SD) 0.36 mmol/l, and it increased significantly (p < 0.001) to 4.66 +/- 0.45 mmol/l on day 5 of therapy. Subgroup analysis of mean serum potassium concentration on day 5 of therapy failed to detect clinically relevant hyperkalemia. In patients with a serum creatinine level equal to or greater than 1.1 mg/dl (K+, 4.83 +/- 0.48 mmol/l), a nonsignificant difference (p = 0.3) in the potassium concentration was noted on day 5 as compared with patients with a serum creatinine level <1.1 mg/dl (K+, 4.63 +/- 0.44 mmol/l). Although diabetics had a higher serum potassium concentration (K+, 4.91 +/- 0.44 mmol/l) than nondiabetics (K+, 4.61 +/- 0.44 mmol/l), the difference was not statistically significant (p = 0.055). Patients aged >/=50 years (K+, 4.82 +/- 0.59 mmol/l) had a significantly different (p = 0.046) serum potassium concentration on day 5 than patients aged <50 years (K+, 4.55 +/- 0.28 mmol/l). In contrast, the baseline serum potassium concentration in the control group was 4.37 +/- 0.45 mmol/l, and it decreased (p = 0.1) to 4.22 +/- 0.4 mmol/l on 5 days of drug therapy. Trimethoprim-sulfamethoxazole therapy, when used to treat a variety of infections, leads to an increase in serum potassium concentration in most patients. After 5 days of therapy with this drug, the treatment group developed a statistically significant rise in the serum potassium concentration as compared with the control group. However, severe hyperkalemia (K+ >/=5.5 mmol/l) occurred in only 3 patients (6%) treated with trimethoprim-sulfamethoxazole. In addition, none of the subgroups of treated patients developed clinically important hyperkalemia. This suggests that outpatients, in contrast to acquir

Topics: Ambulatory Care; Anti-Infective Agents; Female; Humans; Hyperkalemia; Male; Middle Aged; Potassium; Prospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of standard-dose trimethoprim-sulfamethoxazole on serum potassium concentration in hospitalized patients.. Prospective chart review.. Community-based teaching hospital.. 105 patients with various infections were hospitalized and treated. Eighty patients treated with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, < or = 320 mg/d; sulfamethoxazole, < or = 1600 mg/d) composed the treatment group; 25 patients treated with other antibiotic agents served as the control group.. Serum sodium, potassium, and chloride concentrations; serum carbon dioxide content; anion gap; blood urea nitrogen level; and serum creatinine level.. The serum potassium concentration in the treatment group (mean +/- SD) was 3.89 +/- 0.46 mmol/L (95% CI, 3.79 to 3.99 mmol/L), and it increased by 1.21 mmol/L (CI, 1.09 to 1.32 mmol/L) 4.6 +/- 2.2 days after trimethoprim-sulfamethoxazole therapy was initiated. Blood urea nitrogen levels increased from 7.92 +/- 5.7 mmol/L (CI, 6.67 to 9.16 mmol/L) to 9.2 +/- 5.8 mmol/L (CI, 7.9 to 10.5 mmol/L), and serum creatinine levels increased from 102.5 +/- 49.5 mumol/L (CI, 91.4 to 113.6 mumol/L) to 126.1 +/- 70.7 mumol/L (CI, 110.3 to 141.9 mumol/L). Patients with a serum creatinine level of 106 mumol/L (1.2 mg/dL) or more developed a higher peak potassium concentration (5.37 +/- 0.59 mmol/L [CI, 5.15 to 5.59 mmol/L]) than patients with a serum creatinine level of less than 106 mumol/L (4.95 +/- 0.48 mmol/L [CI, 4.80 to 5.08 mmol/L]). Patients with diabetes had a slightly higher peak potassium concentration (5.14 +/- 0.45 mmol/L [CI, 4.93 to 5.39 mmol/L]) than did patients without diabetes (5.08 +/- 0.59 mmol/L [CI, 4.93 to 5.23 mmol/L]), but the difference was not statistically significant. The serum potassium concentration in the control group was 4.33 +/- 0.45 mmol/L (CI, 4.15 to 4.51 mmol/L), and it decreased nonsignificantly over 5 days of therapy.. Standard-dose trimethoprim-sulfamethoxazole therapy used to treat various infections leads to an increase in serum potassium concentration. A peak serum potassium concentration greater than 5.0 mmol/L developed in 62.5% of patients; severe hyperkalemia (peak serum potassium concentration > or = 5.5 mmol/L) occurred in 21.2% of patients. Patients treated with standard-dose trimethoprim-sulfamethoxazole should be monitored closely for the development of hyperkalemia, especially if they have concurrent renal insufficiency (serum creatinine level > or = 106 mumol/L).

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Blood Urea Nitrogen; Creatinine; Female; Hospitalization; Humans; Hyperkalemia; Infections; Male; Middle Aged; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX versus amoxicillin and determined if this risk is modified by a patient's baseline kidney function [estimated glomerular filtration rate (eGFR)].. We conducted a population-based cohort study in Ontario, Canada involving adults ≥66 years of age newly treated with TMP-SMX (n = 58 999) matched 1:1 with those newly treated with amoxicillin (2008-2020). The primary outcome was a hospital encounter with hyperkalemia defined by a laboratory serum potassium value ≥5.5 mmol/L within 14 days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury (AKI) and all-cause hospitalization. Risk ratios (RRs) were obtained using a modified Poisson regression.. A hospital encounter with hyperkalemia occurred in 269/58 999 (0.46%) patients treated with TMP-SMX versus 80/58 999 (0.14%) in those treated with amoxicillin {RR 3.36 [95% confidence interval (CI) 2.62-4.31]}. The absolute risk of hyperkalemia in patients treated with TMP-SMX versus amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for an eGFR ≥60 ml/min/1.73 m2, 0.42% for eGFR 45-59, 0.85% for eGFR 30-44 and 1.45% for eGFR <30; additive interaction P < .001). TMP-SMX versus amoxicillin was associated with a higher risk of a hospital encounter with AKI [RR 3.15 (95% CI 2.82-3.51)] and all-cause hospitalization [RR 1.43 (95% CI 1.34-1.53)].. The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX versus amoxicillin and the risk was highest in patients with a low eGFR.

Topics: Acute Kidney Injury; Adult; Amoxicillin; Cohort Studies; Hospitals; Humans; Hyperkalemia; Ontario; Potassium; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR.. To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr.. This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date.. The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.. The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance.. A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003).. Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

Topics: Adult; Aged; Baclofen; Cohort Studies; Creatinine; Cystatin C; Digoxin; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Since trimethoprim (TMP) dose-dependently inhibits the excretion of potassium, a population kinetic-pharmacodynamic analysis was performed to establish an adequate dosing schedule and characterize factors of hyperkalaemia. Dataset was constructed using a retrospective observational cohort of hospitalized patients (>18 years) with oral sulfamethoxazole/trimethoprim formulation. The model integrated a kinetic model for TMP, a urinary TMP concentration-response curve and a kinetic model for serum potassium using an indirect response model. The model was a function of body weight, renal function, serum potassium levels and TMP dosing schedule. We evaluated covariates by the stepwise forward and backward selection methods. The Monte Carlo simulation determined the probability of hyperkalaemia (>5.5 or >6.0 meq/L) according to the dosing schedule, renal function and covariates. This study included 317 patients [age 62 (42-72) years] with 4359 serum potassium levels. The significant covariate was non-steroidal anti-inflammatory drugs (NSAIDs), with a 72.3% reduction in 50% inhibitory concentration. Monte Carlo simulation revealed that high-dose TMP (400 mg thrice daily) co-administered with NSAIDs led to mild hyperkalaemia (>10%) and severe hyperkalaemia (approximately 5%), regardless of renal function. In conclusion, clinicians should pay attention to hyperkalaemia with TMP high-dose and co-administered NSAIDs.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Humans; Hyperkalemia; Middle Aged; Potassium; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) use in immunocompromised patients can cause dose-dependent electrolyte irregularities including hyponatremia, hyperkalemia, and metabolic acidosis. We report a case of isolated hyponatremia caused by low-dose TMP-SMX use in an immunocompetent patient that mimicked the syndrome of inappropriate antidiuretic hormone secretion (SIADH).. A 72-year-old woman was admitted to the hospital for acute onset of weakness and ambulatory dysfunction after starting TMP-SMX (160 mg/800 mg). She was found hyponatremic (sodium level, 125 mmol/L, down from 141 mmol/L prior to medication initiation). After ruling out diuretics use, and adrenal and thyroid dysfunction, we started her on intravenous saline infusion to manage her TMP-SMX-induced hyponatremia, and her symptoms resolved.. Electrolyte problems in immunocompromised patients treated for opportunistic infections with high-dose TMP-SMX (≥ 8 mg/kg/d TMP) are well-documented. However, the effects in immunocompetent patients are uncommon when standard dose (< 8 mg/kg/d TMP) is used.. TMP-SMX blocks the aldosterone-mediated sodium reabsorption in the collecting ducts, and the trimethoprim component itself is structurally similar to potassium-sparing diuretics, which block sodium uptake at the distal nephron-both of which can cause hyponatremia.

Topics: Aged; Diuretics; Female; Humans; Hyperkalemia; Hyponatremia; Sodium; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Drug Combinations; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

A70-year-old man, with established hypoadrenalism due to a previous bilateral adrenalectomy, was admitted with recurrent episodes of postural dizziness and presyncope. He had been discharged from hospital 3 weeks earlier on a 1-month course of cotrimoxazole following a diagnosis of prostatitis. His electrolytes on admission showed new onset hyponatraemia and hyperkalaemia.His usual glucocorticoid replacement dose was doubled in view of a presumed diagnosis of hypocortisolaemia. However, the hyperkalaemia persisted. On rereviewing his treatment, we suspected a possible diagnosis of cotrimoxazole-induced hyperkalaemia. Cotrimoxazole was stopped and ciprofloxacin started instead. His fludrocortisone replacement was doubled for 3 days after stopping treatment to decrease his postural symptoms. His postural symptoms improved, his serum potassium decreased to normal levels and he was safely discharged.It is essential to remember that cotrimoxazole, a commonly used antibiotic, can induce a potentially fatal hyperkalaemia especially in patients with known hypoadrenalism.

Topics: Addison Disease; Aged; Humans; Hyperkalemia; Hypoaldosteronism; Male; Potassium; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfamethoxazole/trimethoprim causes hyperkalemia; however, the effect of sulfamethoxazole/trimethoprim dose and co-administered glucocorticoids on hyperkalemia has not been clarified.. This single-center, retrospective, observational cohort, chart review study involving patients (>20 years) who were treated with sulfamethoxazole/trimethoprim was conducted at Tokyo Women's Medical University, Medical Center East from June 2015 to May 2019. Multivariate Cox proportional hazard model was used to identify risk factors for hyperkalemia (serum potassium level > 5.5 mEq/L). Additionally, Kaplan-Meier curve analyzed the cumulative incidence of hyperkalemia focusing on sulfamethoxazole/trimethoprim dose and concomitant use of glucocorticoids with mineralocorticoid activity.. Among 333 patients, 44 (13%) patients developed hyperkalemia associated with sulfamethoxazole/trimethoprim use for over 49 (interquartile range; 17-233) days. We found associations between the time to hyperkalemia development and sulfamethoxazole/trimethoprim dose (hazard ratio 1.238, 95% confidence interval 1.147-1.338, p < 0.001) and glucocorticoid use (hazard ratio 0.678, 95% confidence interval 0.524-0.877, p = 0.003). Interestingly, the Kaplan-Meier curves revealed that the concomitant use of glucocorticoids did not attenuate the risk of hyperkalemia in patients receiving high-dose sulfamethoxazole/trimethoprim (p = 0.747), whereas concomitant use of glucocorticoids significantly reduced the risk of hyperkalemia in patients receiving non-high dose sulfamethoxazole/trimethoprim (p < 0.001).. High-dose sulfamethoxazole/trimethoprim is a significant predictor of hyperkalemia. The effect of glucocorticoids on hyperkalemia varies depending on the sulfamethoxazole/trimethoprim dose.

Topics: Female; Glucocorticoids; Humans; Hyperkalemia; Potassium; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+ 0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 to < 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+ 0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.

Topics: Anti-Bacterial Agents; Ceftriaxone; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Middle Aged; Netherlands; Pneumocystis carinii; Pneumonia, Pneumocystis; Potassium; Trimethoprim, Sulfamethoxazole Drug Combination

Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Data was collected retrospectively from patients in five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 ≤ 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biomarkers; Ceftriaxone; Drug Monitoring; Female; Guideline Adherence; Hospitalization; Humans; Hyperkalemia; Inpatients; Male; Middle Aged; Potassium; Practice Guidelines as Topic; Practice Patterns, Physicians'; Predictive Value of Tests; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) is a bactericidalantibiotic. The most common adverse effect of TMP/SMX is skinrashes and gastrointestinal symptoms. Although hyperkalemia canoccur with TMP/SMX component but hyponatremia is uncommon. A55- year old woman, known case of rheumatoid arthritis, presentedwith fever and mild dyspnea. According to diagnostic work upthe infection with pneumocystis jirovecii was confirmed. TMP/SMX was started but after 10 days the patient acutely representedwith nausea and became lethargic. The laboratory studies showedmoderate hyperkalemia and severe hyponatremia. TMP/SMX wasstopped and alternative treatment started. Upon discontinuation ofthe drug, serum sodium and potassium levels were both changed tonormal. Hyponatremia as a life threatening adverse effect appearsto be rare with TMP-SMX therapy, but clinicians should be awareof electrolyte disturbances developed with this drug and electrolytemonitoring should always be considered.

Topics: Female; Humans; Hyperkalemia; Hyponatremia; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as prophylaxis against Pneumocystis pneumonia (PCP) in renal transplant recipients. The optimal duration of prophylaxis is unknown. Longer duration of prophylaxis may increase the risk of adverse effects. The aim of this retrospective observational cohort study was to assess the impact of increasing duration of TMP-SMX prophylaxis from 3 to 6 months after transplant on drug-resistant urinary tract infection (UTI), hyperkalemia, peripheral blood cytopenias, and incidence of PCP. MATERIAL AND METHODS Patients transplanted over a 4.5-year period before and after a change in protocol from 3- to 6-months TMP-SMX prophylaxis in our unit were grouped according to planned duration of prophylaxis, and results were analyzed on an intention-to-treat basis. Baseline characteristics, laboratory values, and all urine microbiology results in the 6 months after transplant were analyzed. RESULTS The overall UTI incidence rate was higher in the 3-month (3-m) treatment group than the 6-month (6-m) treatment group (0.52 vs. 0.33 UTI per 100 patient days; rate ratio 1.56 [95% CI 1.27-1.95]). However, this was not attributable to TMP-SMX: the incidences were significantly different in months 0-3 but not months 4-6. Twenty-eight multi-resistant UTIs occurred in the 3-m group, but there were none in the 6-m group (p=0.004). There were no significant differences in renal function, serum potassium, or cytopenias during the first 6 months. There were 15 cases of PCP in the 3-m group, 3 cases in the 6-m group, and no cases during prophylaxis. CONCLUSIONS Extending the duration of TMP-SMX prophylaxis was not associated with change in frequency of UTIs or multi-drug-resistant UTIs, nor was it associated with increased adverse events. TMP-SMX is an effective PCP prophylaxis, and these data support recommendations to extend the duration of prophylaxis after transplant.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cohort Studies; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Hyperkalemia; Kidney Transplantation; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Cotrimoxazole is associated with the development of hyponatremia, hyperkalemia and elevated serum creatinine, especially when combined with inhibitors of the renin-angiotensin-aldosterone system (RAAS).. We evaluated whether high-grade glioma patients taking renin-angiotensin-aldosterone system inhibitors receiving low-dose cotrimoxazole for. We conducted a retrospective chart review of adult neuro-oncology patients treated for WHO Grade III or IV glioma between 2013 and 2016. Patient serum Na, K, creatinine, and eGFR were compared (renin-angiotensin-aldosterone system vs. non-renin-angiotensin-aldosterone system) using the chi-square test. Binary logistic regression analysis was then performed to account for differences between cohorts.. Of 63 patients (35 non-renin-angiotensin-aldosterone system, 28 renin-angiotensin-aldosterone system), patients in the renin-angiotensin-aldosterone system cohort were more likely to experience a laboratory disturbance (odds ratio=3.17,. Adding low-dose cotrimoxazole for

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Antibiotic Prophylaxis; Creatinine; Drug Interactions; Female; Glioma; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Middle Aged; Neoplasm Grading; Pneumonia, Pneumocystis; Potassium; Renin-Angiotensin System; Retrospective Studies; Sodium; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalaemia is a potentially life-threatening condition frequently encountered in hospitalised patients. Among the many causes of hyperkalaemia, drugs have often been implicated. In the South African context, with the high burden of HIV, there is an increased incidence of opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), and consequently many patients receive high doses of trimethoprim-sulfamethoxazole. A lesser-known side-effect of the trimethoprim component of this combination antibiotic is hyperkalaemia. We report a case in which life-threatening hyperkalaemia developed after institution of high-dose co-trimoxazole for PJP.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Female; HIV Infections; Humans; Hyperkalemia; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population.. Cohort study.. UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database.. Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015.. The outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics.. Among a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury.. Trimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.

Topics: Acute Kidney Injury; Age Factors; Aged; Anti-Infective Agents, Urinary; England; Female; Humans; Hyperkalemia; Male; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX.. In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients' age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), β-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed.. The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR <60 mL/min/1.73 m(2), adjusted OR 4.62). Moreover, in the subpopulation of patients with renal insufficiency, ACEi/ARB use was considered to be a major risk factor for hyperkalemia (adjusted OR 3.96).. Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Renal Insufficiency; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia.. We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. 1, 1994, and Dec. 31, 2011. 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). For each case, we identified up to 4 controls matched by age and sex. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index.. Of the 11,968 patients who died of sudden death while receiving spironolactone, we identified 328 whose death occurred within 14 days after antibiotic exposure. 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). 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.. The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. When clinically appropriate, alternative antibiotics should be considered in these patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Case-Control Studies; Confidence Intervals; Death, Sudden; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hyperkalemia; Male; Mineralocorticoid Receptor Antagonists; Odds Ratio; Ontario; Risk Factors; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Death, Sudden; Female; Humans; Hyperkalemia; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Cellulitis; Humans; Hyperkalemia; Male; Middle Aged; Potassium; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges.. To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections.. Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint.. From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01).. Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone Diseases, Infectious; Creatinine; Female; Health Care Costs; Humans; Hyperkalemia; Length of Stay; Male; Middle Aged; Potassium; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Angiotensin Receptor Antagonists; Drug Interactions; Electrocardiography; Female; Humans; Hyperkalemia; Intraoperative Complications; Mastoid; Trimethoprim, Sulfamethoxazole Drug Combination; Tympanoplasty

To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death.. Population based nested case-control study.. Ontario, Canada, from 1 April 1994 to 1 January 2012.. Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes.. 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.. Of 39,879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. 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). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. 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.. In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.

Topics: Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Infective Agents, Urinary; Case-Control Studies; Death, Sudden; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hyperkalemia; Male; Odds Ratio; Ontario; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) for the empiric treatment of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections has been evaluated for efficacy, but characterization of adverse reactions is lacking.. To describe adverse reactions associated with high-dose TMP-SMX therapy, a retrospective medical record review of outpatients receiving TMP-SMX was conducted. Each episode (case) of a patient receiving high-dose TMP-SMX (at least 4 double-strength tablets per day) was matched by next closest prescription number with a patient (control) receiving standard-dose TMP-SMX.. 982 cases were reviewed; 491 in each arm. At least one adverse drug reaction (ADR) occurred in 9.1% of patients. There was a significant difference in the incidence for any ADR between high-dose and standard-dose groups (13.0% vs 5.09%, respectively; p<0.0001). More patients taking high-dose TMP-SMX developed hyperkalemia (3.46% vs 0.81%, p=0.0066), acute renal injury (3.67% vs 1.63%, p=0.044), and rash (1.83% vs 0.20%, p=0.021). Patients receiving high-dose TMP-SMX had significantly higher rates of electrolyte abnormality ADR (5.09% vs 1.63%, p=0.0021), gastrointestinal ADR (5.30% vs 2.24%, p=0.011), renal ADR (3.67% vs 1.63%, p=0.044), central nervous system ADR (2.65% vs 0.81%, p=0.047), and hypersensitivity (2.24% vs 0.41%, p=0.022). Concomitant receipt of an angiotensin-converting enzyme (ACE) inhibitor was a univariate variable associated with hyperkalemia, and advanced age and receipt of high-dose TMP-SMX were independent variables.. ADRs such as hyperkalemia are more likely to be associated with the use of high-dose TMP-SMX in the ambulatory setting. Clinicians should use caution when initiating high-dose TMP-SMX and consider laboratory monitoring in patients of advanced age or those receiving concomitant ACE inhibitor therapy.

Topics: Adult; Age Factors; Aged; Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Anti-Infective Agents; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Female; Humans; Hyperkalemia; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient.

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Diuretics; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Humans; Hyperkalemia; Renal Dialysis; Sotalol; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse events associated with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) for outpatient infections, particularly those likely caused by community-acquired methicillin-resistant Staphylococcus aureus, have not been adequately characterized.. Describe hyperkalemia and acute renal injury associated with high-dose TMP-SMX.. An electronic medical record database retrospective study was conducted of outpatients receiving high-dose or low-dose TMP-SMX, comparing the incidences of hyperkalemia and acute renal injury.. Of 6162 patients, more developed hyperkalemia (3.06% vs 1.05%, P < .0001) or acute renal injury (1.99% vs 0.700%, P = .0001) in the high-dose TMP-SMX group. Variables independently associated with hyperkalemia included age >58 years (odds ratio [OR] = 3.44; 95% CI = 1.86-7.0; P < .0001), concomitant receipt of an NSAID (OR = 1.71; 95% CI = 1.02-2.79; P = .044) or an ACE inhibitor (OR = 3.27; 95% CI = 2.06-5.14; P < .0001), high-dose TMP-SMX prescribed (OR = 2.92; 95% CI = 1.85-4.60; P < .0001), and baseline elevated serum creatinine (OR = 45.1; 95% CI = 21.7-93.2; P < .0001). Variables independently associated with acute renal injury included concomitant receipt of an ACE inhibitor (OR = 2.36; 95% CI = 1.01-5.24; P = .048) or a potassium supplement (OR = 4.10; 95% CI = 1.45-10.1; P = .010), high-dose TMP-SMX prescribed (OR = 3.70; 95% CI = 1.70-8.12; P = .0012), and baseline elevated serum creatinine (OR = 2110; 95% CI = 724-7980; P < .0001).. Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose TMP-SMX.

Topics: Acute Kidney Injury; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Creatinine; Female; Humans; Hyperkalemia; Incidence; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Potassium; Retrospective Studies; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with renal failure who are taking trimethoprim have an increased risk of developing hyperkalemia, which can cause muscle weakness. In patients with postpolio syndrome, a normal creatinine level could be abnormally high, renal failure is possible because of lack of creatinine production, and the muscle weakness from resultant hyperkalemia could be more severe because of their underlying condition. This abnormally high creatinine level has been termed from this point relative renal failure. The objective of the study was to review a case in which relative renal failure and hyperkalemia caused muscle weakness that manifested as shortness of breath and confusion with electrocardiographic changes. A dehydrated patient with relative renal failure and postpolio syndrome had taken trimethoprim-sulfamethoxazole that caused symptomatic hyperkalemia. The patient presented with muscle weakness, shortness of breath, and confusion, with her postpolio syndrome compounding the situation and likely making the muscle weakness more severe. A patient on trimethoprim with renal failure is at an increased risk of developing hyperkalemia. Patients with postpolio syndrome could have severe muscle weakness from the hyperkalemia and could have renal failure even with a normal creatinine level. This case report will remind treating physicians to evaluate such patients for hyperkalemia if they present with muscle weakness, especially if the patient has renal failure and is on trimethoprim.

Topics: Aged, 80 and over; Creatinine; Electrocardiography; Female; Humans; Hyperkalemia; Postpoliomyelitis Syndrome; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

A 76-year-old man was admitted to our hospital because of severe anemia. Routine screening revealed a sigmoid adenocarcinoma, and he underwent sigmoidectomy. Post-operatively, he developed rapidly progressive glomerulonephritis. He was positive for myeloperoxidase anti-neutrophil cytoplasmic antibody. A renal biopsy revealed idiopathic crescentic glomerulonephritis of the pauci-immune type. He was treated with methylprednisolone semi-pulse therapy with clinical improvement. After the steroid pulse therapy, he was given oral prednisolone, 40 mg per day, and oral trimethoprim (TMP), 160 mg, and sulfamethoxazole (SMX), 800 mg twice weekly for chemoprophylaxis against pneumocystis pneumonia. One month after the initiation of TMP/SMX, he developed hyperkalemia and hyponatremia. His transtubular K gradient was low, and urinary potassium excretion was decreased. On the other hand, plasma renin activity and plasma aldosterone concentrations were within normal limits. These results suggested that TMP acted similarly to a potassium-sparing diuretic amiloride and reduced renal potassium excretion. Administration of calcium polystyrene sulfonate resulted in correction of the hyperkalemia without discontinuation of TMP/SMX. We emphasize that patients with impaired renal function are at the significant risk of developing trimethoprim-induced hyperkalemia even with chemoprophylaxis.

Topics: Adenocarcinoma; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibiotic Prophylaxis; Glomerulonephritis; Humans; Hyperkalemia; Immunocompromised Host; Male; Pneumonia, Pneumococcal; Postoperative Complications; Sigmoid Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Female; Hospitalization; Humans; Hyperkalemia; Incidence; Ontario; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Catheterization; Coronary Angiography; Diagnosis, Differential; Electrocardiography; Feeding Behavior; Heart Conduction System; Humans; Hyperkalemia; Lisinopril; Male; Musa; Myocardial Infarction; Potassium; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.. Population based nested case-control study.. Ontario, Canada, from 1 April 1992 to 1 March 2010.. Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date.. Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia.. During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4). Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

Topics: Aged; Aged, 80 and over; Amoxicillin; Anti-Infective Agents, Urinary; Case-Control Studies; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hyperkalemia; Logistic Models; Male; Mineralocorticoid Receptor Antagonists; Nitrofurantoin; Norfloxacin; Odds Ratio; Ontario; Patient Admission; Risk; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Female; Humans; Hyperkalemia; Male; Mineralocorticoid Receptor Antagonists; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination

The simultaneous use of beta adrenergic receptor blockers (beta-blockers) and trimethoprim-sulfamethoxazole (TMP-SMX) may confer a high risk of hyperkalemia.. Two nested case-control studies were conducted to examine the association between hospitalization for hyperkalemia and the use of TMP-SMX in older patients receiving beta-blockers. Linked health administrative records from Ontario, Canada, were used to assemble a cohort of 299,749 beta-blockers users, aged 66 years or older and capture data regarding medication use and hospital admissions for hyperkalemia.. Over the study period from 1994 to 2008, 189 patients in this cohort were hospitalized for hyperkalemia within 14 days of receiving a study antibiotic. Compared with amoxicillin, the use of TMP-SMX was associated with a substantially greater risk of hyperkalemia requiring hospital admission (adjusted odds ratio, 5.1; 95% confidence interval [CI], 2.8 to 9.4). No such risk was identified with ciprofloxacin, norfloxacin, or nitrofurantoin. When dosing was considered, the association was greater at higher doses of TMP-SMX. When the primary analysis was repeated in a cohort of non-beta-blocker users, the risk of hyperkalemia comparing TMP-SMX to amoxicillin was not significantly different from that found among beta-blocker users.. Although TMP-SMX is associated with an increased risk of hyperkalemia in older adults, these findings show no added risk when used in combination with beta-blockers.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Anti-Infective Agents; Biomarkers; Case-Control Studies; Female; Hospitalization; Humans; Hyperkalemia; Logistic Models; Male; Odds Ratio; Patient Admission; Polypharmacy; Potassium; Risk Assessment; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 7-10 days and has been reported in 20%-50% of patients receiving trimethoprim-sulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due, in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on trimethoprim-related hyperkalaemia.. Thirty patients qualified for inclusion and were reviewed. Patients were divided into two groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients); and the other group received trimethoprim-sulfamethoxazole alone (12 patients).. The two groups were comparable at baseline, except for the severity of the P. jiroveci pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group is surprising and was counter to our expectation.. Although it is possible that there is an unexplained interaction between trimethoprim and prednisolone, we postulate that our observation is a result of the catabolic effect of prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone appear to be more likely to develop hyperkalaemia than patients treated with trimethoprim-sulfamethoxazole alone.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of intractable hyperkalaemia in an elderly patient with myeloma, who received conventional dose of trimethoprim-sulfamethoxazole and hyperkalaemia resolved following therapy with fludrocortisone. We recommend monitoring of serum potassium in high-risk patients receiving conventional doses of trimethoprim-sulfamethoxazole for 5 or more days.

Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Fludrocortisone; Humans; Hyperkalemia; Male; Multiple Myeloma; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.. To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.. Three population-based, nested case-control studies.. Ontario, Canada, from January 1, 1994, to December 31, 2000.. All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).. Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.. During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).. Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Asthmatic Agents; Anti-Infective Agents; Antihypertensive Agents; Case-Control Studies; Clarithromycin; Contraindications; Digoxin; Diuretics; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Female; Glyburide; Hospitalization; Humans; Hyperkalemia; Hypoglycemia; Male; Ontario; Trimethoprim, Sulfamethoxazole Drug Combination

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders.. Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination.. Electrolyte disorders (Na < 135 mEq/l and/or K > 5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7 +/- 24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7 +/- 84.2 mg vs. 101.9 +/- 9.38 mg, p = 0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP < 80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr > 1.2 mg/dl), compared with 17.5% of patients with normal renal function (p = 0.0008). Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively.. Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX. These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX.

Topics: Anti-Infective Agents; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Potassium; Retrospective Studies; Sodium; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Humans; Hyperkalemia; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalemia is a serious electrolyte disorder and is a frequent finding in renal transplant recipients. Trimethoprim-induced hyperkalemia has been increasingly reported in recent years. We describe two renal transplant recipients who developed end-stage renal disease secondary to familial Mediterranean fever and presented with severe hyperkalemia secondary to the use of standard dose of trimethoprim. One of the patients had potential underlying adrenal insufficiency, which might be a contributing factor for the development of hyperkalemia. We concluded that renal transplant patients receiving even the standard dose of trimethoprim should be monitored closely for the development of hyperkalemia. They should be recognized as a group with increased risk in regard to their concurrent renal insufficiency, concomitant use of cyclosporine, and associated tubulointerstitial disease. Patients with secondary amyloidosis are at even greater risk, and subclinical adrenal insufficiency may be an underlying risk factor for the development of severe, life-threatening hyperkalemia among this group of patients.

Topics: Adult; Amyloidosis; Anti-Infective Agents; Familial Mediterranean Fever; Humans; Hyperkalemia; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Combinations; Female; Humans; Hyperkalemia; Hyponatremia; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced hyperkalemia is an important but often overlooked problem encountered commonly in clinical practice. It may occur in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient should include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. Medications generally produce hyperkalemia either by causing redistribution of potassium (beta2 -adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by (1) interfering with the production and/or secretion of aldosterone (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or (2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal insufficeiency is generally required to cause hyperkalemia, an elevated serum potassium concentration in a patient with mild-to-moderate renal failure should not be ascribed to renal failure alone. A careful search for "hidden" potassium loads and for causes of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is important to recognize that the causes of hyperkalemia may be additive. Patients may have more than one cause of hyperkalemia at the same time. Therefore, all potential causes of hyperkalemia, including drugs, should be systematically evaluated in every hyperkalemic patient.

Topics: Adult; AIDS-Related Opportunistic Infections; Aldosterone; Anti-Infective Agents; Diagnosis, Differential; Electrocardiography; Fluid Shifts; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Potassium; Tissue Distribution; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acidosis, Renal Tubular; Anti-Infective Agents, Urinary; Electrochemistry; Escherichia coli Infections; Humans; Hydrogen-Ion Concentration; Hyperkalemia; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Anti-Infective Agents; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents, Urinary; Humans; Hyperkalemia; Hypoaldosteronism; Male; Renin; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Anti-Infective Agents; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hyperkalemia; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Humans; Hyperkalemia; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

A case is reported of a 96-year-old woman with congestive heart failure, hypertension, and chronic obstructive pulmonary disease who presented with altered mental status and severe hyperkalemia, a serum potassium 9.3 meq/L, and electrocardiograph changes. The patient was discharged 1 week prior, with a normal serum potassium, receiving trimethoprim-sulfamethoxazole for urinary tract infection and pneumonia. Serum potassium measurements returned to normal after discontinuation of the drug. Other causes of hyperkalemia were ruled out. Mild hyperkalemia due to trimethoprim-sulfamethoxazole was first reported in 1983 in a 69-year-old woman in whom leukemia with leukopenia developed. In literature to date, mild hyperkalemia in younger geriatric patients has been described. Trimethoprim is thought to act by inhibiting amiloride sensitive sodium channels in the distal nephron and impairing renal potassium secretion in a dose dependent manner. The authors report the case, review the literature, and discuss age-related reduction in renal function as a possible etiology.

Topics: Aged; Female; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of standard-dose trimethoprim/sulfamethoxazole (TMP/SMX) (TMP 160 mg and SMX 800 mg q12h) on the serum potassium concentration.. Retrospective and concurrent study.. A Veterans Affairs Medical Center.. Fifty-three men hospitalized at the Fargo Veterans Affairs Medical Center. Thirty-three patients who received standard-dose TMP/SMX for 3 or more days comprised the study group. Twenty patients who received oral cephradine or amoxicillin for 3 or more days comprised the control group. Patients who received potassium supplements, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, nonsteroidal antiinflammatory drugs, beta-blockers, heparin, known nephrotoxic agents, patients with a serum creatinine concentration of more than 177 mumol/L, and patients with baseline hyperkalemia (serum potassium concentration > 5.1 mmol/L) were excluded.. The serum potassium concentration in the study group was 4.22 +/- 0.40 mmol/L and increased by 0.31 +/- 0.38 mmol/L at the end of therapy (p < 0.001). Twenty-six patients in the study group (78.8%) had an increase in the serum potassium concentration during TMP/SMX therapy. Fourteen of these patients had follow-up serum potassium concentrations obtained after completion of therapy. The serum potassium concentration returned to baseline in 10 of these patients. The serum creatinine concentration also increased during therapy. However, the correlation between the increase in the serum potassium concentration and the increase in the serum creatinine concentration was weak (Pearson r = 0.29). The serum potassium in the control group was 4.34 mmol/L and remained essentially unchanged during therapy.. Therapy with standard-dose TMP/SMX is associated with a slight increase in the serum potassium concentration. Routine monitoring of the serum potassium concentration in patients who are treated with standard-dose TMP/SMX therapy is unnecessary. However, TMP/SMX should be considered as a possible cause of unexplained hyperkalemia in elderly patients receiving TMP/SMX therapy.

Topics: Aged; Anti-Infective Agents, Urinary; HIV Infections; Humans; Hyperkalemia; Male; Potassium; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents, Urinary; Drug Interactions; Drug Therapy, Combination; Humans; Hyperkalemia; Male; Trimethoprim, Sulfamethoxazole Drug Combination

A 40-year-old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L-1) during high dose treatment with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride-like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, and the combination of ACE-inhibition and potassium-sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE-inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE-inhibitors with other potassium-sparing diuretics.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Infective Agents; Enalapril; Fatal Outcome; Female; Humans; Hyperkalemia; Lung Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Humans; Hyperkalemia; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Humans; Hyperkalemia; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Energy Intake; Hospitalization; Humans; Hyperkalemia; Nutritional Status; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Insufficiency; AIDS-Related Opportunistic Infections; Anti-Infective Agents; HIV Seropositivity; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Humans; Hyperkalemia; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is a fixed-dose antimicrobial agent used in a variety of infections. Adverse reactions are more common in patients with AIDS, but occasionally occur in immunocompetent patients. Renal toxicity is usually a hypersensitivity reaction to the sulfa component, and manifests as interstitial nephritis or sulfa crystallization in the renal tubules. Reversible hyperkalemia is a rarely reported side effect of TMP-SMX therapy attributed to TMP inhibition of potassium secretion in the distal renal tubule in a manner similar to the potassium sparing diuretic, amiloride. In this article, the author reports a case of hyperkalemia associated with TMP-SMK occurring in an elderly man with no other risk factors for hyperkalemia, which resolved upon discontinuation of the drug.

Topics: Aged; Electrolytes; Humans; Hyperkalemia; Male; Potassium; Soft Tissue Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Urea

An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced electrolyte imbalance have been reported in the English-language literature to date. Recently, however, we treated two patients with Pneumocystis carinii pneumonia who developed severe hyponatremia and hyperkalemia on administration of high-dose Tmp-Smx. These electrolyte disturbances were attributable to the direct effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by infusion of a sodium-enriched and potassium-free liquid. Therefore, it is suggested that even after electrolyte disturbances have occurred, high-dose Tmp-Smx therapy may be continued for severe infectious diseases under appropriate electrolyte correction.

Topics: Humans; Hyperkalemia; Hyponatremia; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; AIDS-Related Opportunistic Infections; Fatal Outcome; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Humans; Hyperkalemia; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; Female; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; Aged, 80 and over; Female; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Age Factors; Aged; Female; Humans; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Humans; Hyperkalemia; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Hyperkalaemia with renal tubular dysfunction by oral therapy of sulfamethoxazole-trimethoprim (co-trimoxazole) is described in 2 elderly Japanese patients with lymphoid malignancy, who developed Pneumocystis carinii pneumonia and improved. A high dose of cotrimoxazole induced hyperkalaemia with the elevation of serum creatinine and blood urea, and increased urinary N-acetyl glucosaminase after several days of the drug administration in these patients; one patient became unconscious. Discontinuation of co-trimoxazole normalized serum potassium level and symptoms. A repeated low dose of the drug induced hyperkalaemia. Before the treatment of co-trixomazole, their serum levels of creatinine showed upper limits of normal ranges. In the present study, our cases suggested that patients receiving a high dose of co-trimoxazole should be evaluated for these potential complications during a course of treatment, particularly in elderly patients with preexisting renal dysfunction.

Topics: Aged; Humans; Hyperkalemia; Hyponatremia; Kidney Diseases; Kidney Tubules; Leukemia, T-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration.. Retrospective cohort study.. An urban teaching hospital.. Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded.. Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization.. High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Cohort Studies; Female; Humans; Hyperkalemia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Allopurinol; Amiloride; Aspirin; Drug Combinations; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hyperkalemia; Indomethacin; Male; Nifedipine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination