trimethoprim--sulfamethoxazole-drug-combination and Renal-Insufficiency

Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.. Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.. A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.. Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Glucose; Humans; Hypoglycemia; Infant; Male; Middle Aged; Renal Insufficiency; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

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

To investigate drug concentration of trimethoprim-sulfamethoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe. A 72-year-old man with hypoxemic respiratory failure due to COVID-19 infection was admitted to the intensive care unit for invasive mechanical ventilation. The patient developed acute renal failure that required RCA-CVVH. Pulmonary co-infection with PJP was diagnosed, and a high TMP-SMX dose was initiated according to (inter)national guidelines with dose reduction after 3 days because of renal failure. Population pharmacokinetics were assessed for TMP and SMX as well as clearance by RCA-CVVH, volume of distribution, and time above threshold levels for measured plasma concentrations.. During renal failure requiring RCA-CVVH, a corresponding dose reduction of TMP-SMX to 320/1,600 mg twice a day, according to current Dutch SWAB and Dutch Association of Hospital Pharmacists guidelines, resulted in unintended under-dosing with sub-therapeutic TMP-SMX concentrations. Pharmacokinetic modeling and dose adjustment of TMP-SMX to 640/3,200 mg 3 times daily resulted in steady-state TMP-SMX peak concentrations associated with efficacy against PJP. Hence, the patient was successfully weaned from the ventilator and discharged.. We hypothesize that our new dose recommendation of 640/3,200 mg TMP-SMX 3 times daily is associated with an increased probability of critical patients being successfully liberated from mechanical weaning following PJP pneumonia and COVID-19 infection.

Topics: Aged; Coinfection; Continuous Renal Replacement Therapy; COVID-19; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Renal Insufficiency; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to determine the rates of trimethoprim/sulfamethoxazole (TMP/SMX)-associated pseudo-elevation and true nephrotoxicity by comparison of creatinine-estimated and cystatin C-estimated GFRs (glomerular filtration rates) before and after TMP/SMX administrations.. Patients in whom serum creatinine and cystatin C were simultaneously measured are the cohort of this study. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by ≥ 20% were defined as true nephrotoxicity. A decreasing of creatinine-estimated GFR posterior to TMP/SMX by ≥ 20% and a decreasing of cystatine C-estimated GFR posterior to TMP/SMX by < 20% were defined as pseudo-elevation.. A total of 66 patients were enrolled. Within the 19 patients in whom serum creatinine and cystatin C were measured simultaneously both before and after TMP/SMX administrations, 10 patients (52.6%) had nephrotoxicity. Fewer random error and systematic bias between creatinine- and cystatine C-estimated GFR were observed after TMP/SMX than before TMP/SMX by Bland-Altman analysis.. Using cystatin C, we reveled TMP/SMX-associated nephrotoxicity is not uncommon. We should equally pay attention to TMP/SMX-associated nephrotoxicity and pseudo-elevation. In spite of pseudo-elevation, creatinine-estimated GFR after receiving TMP/SMX is ironically reliable as surrogate maker for renal clearance.

Topics: Creatinine; Drug-Related Side Effects and Adverse Reactions; Glomerular Filtration Rate; Humans; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Nitrofurantoin is recommended as a first-line antibiotic for the treatment of urinary tract infections (UTIs). However, it is contraindicated in patients with a creatinine clearance (Clcr) less than 60 mL/min. In 2015, the American Geriatrics Society updated the Beers criteria to recommend nitrofurantoin for short-term use in patients with a Clcr greater than or equal to 30 mL/min. It is unknown if nitrofurantoin can be safely and effectively used in a frail patient population with a high incidence of UTIs and frequent use of antibiotics. It is important to have treatment options other than fluoroquinolones and sulfamethoxazole/trimethoprim for patients with recurrent UTIs and frequent antibiotic use to sustain optimal antimicrobial stewardship practices. This study evaluated the safety and efficacy of nitrofurantoin for UTIs in medically complex patients with renal impairment living in a community setting, and it highlights the potential role for pharmacists to encourage antimicrobial stewardship.

Topics: Aged; Anti-Bacterial Agents; Fluoroquinolones; Frail Elderly; Humans; Independent Living; Nitrofurantoin; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Biopsy; Drug Hypersensitivity Syndrome; Fatal Outcome; Fluorescent Antibody Technique; Glucocorticoids; Herpesvirus 6, Human; Humans; Kidney; Male; Middle Aged; Renal Dialysis; Renal Insufficiency; Roseolovirus Infections; Trimethoprim, Sulfamethoxazole Drug Combination

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

A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Drug Hypersensitivity Syndrome; Eosinophilia; Herpesvirus 6, Human; Humans; Male; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

Topics: Acidosis, Lactic; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anemia, Hemolytic; Antifungal Agents; Cryptococcus neoformans; Drug Therapy, Combination; Female; Humans; Male; Meningitis, Cryptococcal; Renal Insufficiency; Thrombocytopenia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic.. We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m(2)) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim-sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m(2)).. The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36-0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25-0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses.. In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Ciprofloxacin; Female; Glomerular Filtration Rate; Humans; Nitrofurantoin; Norfloxacin; Renal Insufficiency; Retrospective Studies; Sex Factors; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Bethanechol; Biopsy; Diagnosis, Differential; Female; Fluoroquinolones; Humans; Ill-Housed Persons; Kidney; Kidney Function Tests; Malacoplakia; Middle Aged; Muscarinic Agonists; Organ Size; Prognosis; Renal Dialysis; Renal Insufficiency; Substance-Related Disorders; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Nephrogenic adenoma is an uncommon urothelial lesion that has been associated with chronic inflammation and surgical manipulation of the urinary tract. Several cases of vesical nephrogenic adenoma in patients with a history of renal transplantation have been reported. The present case report reviewed the management of recurrent nephrogenic adenoma in a 6-year-old boy with history of renal transplantation 3 years before the diagnosis of nephrogenic adenoma. After multiple surgical resections for recurrent nephrogenic adenoma, the lesion finally resolved with long-term treatment with ibuprofen (Motrin) and trimethoprim and sulfamethoxazole (Septra).

Topics: Adenoma; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Child; Endoscopy; Humans; Ibuprofen; Inflammation; Kidney Transplantation; Male; Recurrence; Renal Insufficiency; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Bladder Neoplasms

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

HIV infections are a growing concern in the elderly as a result of improvements in therapeutics and monitoring, which have extended the life span for this HIV-infected population. Elderly patients potentially are more complicated to treat than younger HIV-infected individuals because of comorbidities and the physiological effects of aging on pharmacokinetics and pharmacodynamics. The patient, a 67-year-old African-American HIV-infected male, presents to the transitional care unit of university-affiliated hospital refusing to take medications and undergo laboratory testing, including blood draws. This patient's treatment is further complicated by poor renal function, medications with potential interactions, and a recent diagnosis of depression. This case demonstrates treatment and monitoring of an elderly patient with HIV and reveals the complications associated with this disease state. Specifically, it identifies nonadherence to medications and a lack of laboratory results, which affect the efficacy of treatment and monitoring, medication adjustments based on metabolism and renal excretion, monitoring of adverse effects of HIV and antiretroviral therapy, and comorbid conditions that may be linked to HIV and antiretroviral therapy such as depression and bone disease. Education on HIV medications, monitoring, and standards of care for pharmacists working with the geriatric population is warranted and should be emphasized as the HIV-infected elderly population continues to grow.

Topics: Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antihypertensive Agents; Azithromycin; CD4 Lymphocyte Count; Depressive Disorder; Diltiazem; Drug Interactions; Drug Monitoring; HIV Infections; Humans; Hypertension; Lopinavir; Male; Patient Compliance; Pharmacists; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Here we present a case of refractory hypoglycaemia associated with use of the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). This was used to treat Pneumocystis jirovecii pneumonia (PCP) infection. The patient had significant pre-existing renal impairment with a kidney transplant in situ. Refractory hypoglycaemia occurred 5 days after starting the antibiotic and persisted for 36 h after its cessation. SMX contains the same sulphanilamide structural group as the oral hypoglycaemic agents called sulphonureas. SMX could therefore act as an insulin secretagogue. The inappropriately raised insulin and c-peptide levels seen in our patient support this theory. The 5-day asymptomatic period would allow sufficient time for the drug to accumulate and the extended period seen after its cessation would be seen in a dose-dependent side effect. Following 3 days of observation and continuous glycaemic support on the High Dependency Unit she was discharged back to the ward, with no further occurrence of hypoglycaemia.

Topics: Anti-Bacterial Agents; C-Peptide; Female; Humans; Hypoglycemia; Insulin; Kidney Transplantation; Middle Aged; Pneumonia, Pneumocystis; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination; White People

A case of severe dyspnea, hypercalcemia and renal failure secondary to sarcoidosis is reported. The clinical diagnosis of sarcoidosis in a 48-year-old man was confirmed by histology and cytology. Transiently decreased numbers of CD4+ T cells (282/microliter) indicated impaired immunity in the absence of HIV-infection during the acute phase of the disease. Surprisingly, numerous "trophozoites" of Pneumocystis carinii were detected by immunofluorescence staining and PCR in the bronchoalveolar fluid indicating infection or colonization of the lungs. Corticosteroid therapy was administered together with trimethoprim-sulfamethoxazole and rapidly reduced elevated serum calcium and creatinine concentrations. Since airborne person-to-person transmission of P. carinii to susceptible individuals might be possible, patients with sarcoidosis could be a previously unrecognized reservoir for P. carinii distribution in hospitals and in the community at large.

Topics: CD4 Lymphocyte Count; Drug Therapy, Combination; Humans; Hypercalcemia; Immune Tolerance; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisone; Renal Insufficiency; Sarcoidosis, Pulmonary; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Therapy, Combination; Humans; Liver Failure; Male; Middle Aged; Pancytopenia; Renal Insufficiency; Trimethoprim, Sulfamethoxazole Drug Combination

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