trimethoprim--sulfamethoxazole-drug-combination and Acute-Kidney-Injury

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

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antineoplastic Agents, Alkylating; Brain Neoplasms; Diabetes Insipidus, Nephrogenic; Glioblastoma; Humans; Hydrochlorothiazide; Kidney Function Tests; Male; Middle Aged; Nephritis, Interstitial; Sodium Chloride Symporter Inhibitors; Temozolomide; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Crystallization; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Urinalysis; Urine

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Betacoronavirus; Clinical Deterioration; Coinfection; Coronavirus Infections; COVID-19; Fatal Outcome; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Kidney Transplantation; Male; Middle Aged; Pandemics; Pneumonia, Bacterial; Pneumonia, Viral; SARS-CoV-2; Stenotrophomonas maltophilia; Transplant Recipients; 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

Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease.. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis.. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Coinfection; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glomerulosclerosis, Focal Segmental; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Renal Insufficiency, Chronic; Respiration, Artificial; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

A 72-year-old man consulted in November 2012 for abdominal pain in the right upper quadrant. The patient had a history of suspected hepatic amebiasis treated in Senegal in 1985 and has not traveled to endemic areas since 1990. Abdominal CT scan revealed a liver abscess. At first, no parasitological tests were performed and the patient was treated with broad-spectrum antibiotics. Only after failure of this therapy, serology and PCR performed after liver abscess puncture established the diagnosis of hepatic amebiasis. The patient was treated with metronidazole and tiliquinol-tilbroquinol. Amebic liver abscess is the most frequent extra-intestinal manifestation. Hepatic amebiasis 22 years after the last visit to an endemic area is exceptional and raises questions on the mechanisms of latency and recurrence of these intestinal protozoan parasites.

Topics: Acute Kidney Injury; Aged; Antibodies, Protozoan; Antiprotozoal Agents; Bacterial Infections; Diagnostic Errors; Drug Therapy, Combination; Entamoeba histolytica; France; Humans; Liver Abscess, Amebic; Male; Metronidazole; Oxyquinoline; Senegal; Time Factors; Tomography, X-Ray Computed; Travel; Trimethoprim, Sulfamethoxazole Drug Combination; West Indies

Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.

Topics: Acute Kidney Injury; Aged, 80 and over; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Critical Care; Drug Interactions; Fatal Outcome; Female; Humans; Kidney Failure, Chronic; Melphalan; Multiple Myeloma; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Dose adjustment for certain drugs is required in patients with reduced renal function to avoid toxicity as many drugs are eliminated by the kidneys. The aim of this study was to assess whether appropriate dosage adjustments were made in hospitalized patients with renal impairment.. A prospective cross-sectional study was carried out in the internal medicine wards of Tikur Anbessa Specialized Hospital. All patients with creatinine clearance ≤ 59 ml/min admitted to hospital between April and July, 2013 were included in the analysis. Data regarding serum creatinine level, age, sex and prescribed drugs and their dosage was collected from the patients' medical records. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The estimated creatinine clearance was calculated using the Cockcroft- Gault (CG) equation. Guideline for Drug prescribing in renal failure provided by the American College of Physicians was used as the standard for dose adjustment.. Nine percent (73/810) of medical admissions were found to have renal impairment (CrCl  ≤ 59 ml/min). There were 372 prescription entries for 73 patients with renal impairment. Dose adjustment was required in 31 % (115/372) of prescription entries and fifty eight (51 %) prescription entries requiring dose adjustment were found to be inappropriate. Of 73 patients, 54 patient received ≥ 1 drug that required dose adjustment (median 2; range 1-6). Fifteen (28 %) patients had all of their drugs appropriately adjusted while twenty two (41 %) patients had some drugs appropriately adjusted, and seventeen (31 %) of patients had no drugs appropriately adjusted. No patients were documented to have received dialysis.. The findings indicate that dosing errors were common among hospitalized patients with renal impairment. Improving the quality of drug prescription in patients with renal impairment could be of importance for improving the quality of care.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Antifungal Agents; Antihypertensive Agents; Ceftazidime; Cimetidine; Creatinine; Cross-Sectional Studies; Digoxin; Diuretics; Drug Dosage Calculations; Drug Prescriptions; Enalapril; Ethiopia; Female; Fluconazole; Gout Suppressants; Hospitalization; Humans; Male; Medication Errors; Middle Aged; Pharmaceutical Preparations; Prospective Studies; Renal Insufficiency, Chronic; Severity of Illness Index; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Young Adult

Dosing of antibiotics in critically ill patients is challenging. It becomes even more difficult if renal or hepatic impairment ensue. Modern means of renal replacement therapy are capable of removing antibiotics to a higher rate than decades ago, leaving clinicians with a high degree of uncertainty concerning the dose of antibiotics in this patient population. Cotrimoxazole, a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is frequently used in the treatment of several infections including Pneumocystis jirovecii pneumonia (PCP).. Here we describe a patient with acute kidney injury in which we investigated the TMP and SMX levels during the course of an ICU stay. Cotrimoxazole was administered every six hours i.v. in a dose of TMP/SMX 15/75 mg/kg/day. Extended dialysis was performed with a high-flux dialyzer. Blood samples, as well as pre- and postdialyzer samples and aliquots of the collected spent dialysate were collected.Observed peak concentrations (Cmax) were 7.51 mg/l for TMP and 80.80 mg/l for SMX. Decline of blood levels during extended dialysis (TMP 64%; SMX 84%) was mainly due to removal by the dialysis procedure, illustrated by the high dialyzer clearances (median of 4 extended dialysis sessions: TMP 94.0 / SMX 51.0 ml/min), as well as by the absolute amount of both substances in the collected spent dialysate (median of 6 extended dialysis sessions: TMP 556 mg / SMX 130 mg). Within the limitation of a case report our data from 4 consecutive extended dialysis sessions suggest that this procedure substantially removes both TMP and SMX.. Dose reduction, which is usually advocated in patients with acute kidney injury under renal replacement therapy, might lead to significant under-dosing. Pharmacokinetic studies for TMP/SMX dosing in this patient population are necessary to allow adequate dosing.

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Humans; Male; Renal Dialysis; 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

An association between herpes virus reactivations and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is accepted. We report six cases of DRESS with viral reactivation occurring within a single 1-month period. We attempted to find a common factor for these six cases and carried out clinical and virological examinations. Before and after this "epidemic", the mean number of cases of DRESS seen at the same centre was one per quarter, making the occurrence of six cases within a single month all the more remarkable and prompting us to seek an explanation.. All six patients had taken a partly causative medication from different drug classes three to six weeks prior to the start of symptoms and herpes virus was detected in the blood of all of these subjects at the time of DRESS onset (four reactivations and two primary infections), and one patient subsequently displayed herpetic meningoencephalitis 95 days after the initial episode, associated with recurrence of DRESS.. There was no common denominator among these six DRESS patients in terms of either drug class or reactivation of a particular type of herpes virus, which raises the possibility of a single unidentified environmental agent. DRESS does not appear fully explainable in terms of a cellular response to drug antigens but seems rather to result from complex interactions between the drug-induced immune response, viral reactivation and antiviral immune response. Several investigators have reported sequential reactivation of herpes viruses in DRESS. A viral epidemic could thus cause a "DRESS epidemic" in patients on medication.. These cases point to the possible existence of a shared initial environmental factor (infectious or not) that favours reactivation of herpes viruses and induces DRESS in patients on medication. Before and after this "DRESS epidemic", about one patient each quarter was admitted to hospital for DRESS.

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Amoxicillin; Anti-Bacterial Agents; Carbamazepine; Chemical and Drug Induced Liver Injury; Cytomegalovirus; Cytomegalovirus Infections; Disease Outbreaks; Drug Eruptions; Epstein-Barr Virus Infections; Female; France; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Hypereosinophilic Syndrome; Imidazoles; Immunocompromised Host; Male; Middle Aged; Models, Biological; Roseolovirus Infections; Seasons; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation

Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population.. We reviewed complete electronic records for all patients who, during a 3 year period, had received ≥6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available.. Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled.. In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Creatinine; Dialysis; Female; Humans; Incidence; Male; Metabolic Clearance Rate; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Urea

Topics: Acute Kidney Injury; Adult; AIDS-Associated Nephropathy; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Anti-Retroviral Agents; Diagnosis, Differential; HIV Seropositivity; Humans; Male; Medication Adherence; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography; Renal Dialysis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Anti-Infective Agents; Crystallization; Humans; Hydrogen-Ion Concentration; Leg Injuries; Spectrophotometry, Infrared; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Urine

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.

Topics: Acute Kidney Injury; Adult; Azithromycin; Biopsy; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Leucovorin; Male; Methotrexate; Mucositis; Necrosis; Pancytopenia; Plasma; Psoriasis; Recombinant Proteins; Self Medication; Skin Ulcer; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the extent of elimination of trimethoprim (TMP) and sulfamethoxazole (SMX) via continuous venovenous hemodiafiltration (CVVHDF) in 2 critically ill patients with renal failure.. A 62-year-old woman with Pneumocystis jirovecii pneumonia (PCP) was admitted to our intensive care unit for severe acute respiratory distress syndrome. A 77-year-old man was admitted for aortic root replacement and developed septic shock and nosocomial pneumonia due to Stenotrophomonas maltophilia. Both patients developed acute renal failure, necessitating CVVHDF. They were treated with intravenous TMP/SMX adapted to renal function. The first patient received TMP 6.4 mg/kg/day and SMX 32 mg/kg/day, corresponding to 50% of the recommended high-dose TMP/SMX regimen in PCP patients. The second patient received TMP 1.7 mg/kg/day and SMX 8.6 mg/kg/day, corresponding to 50% of the usual dose in bacterial infections. We determined peak and trough serum TMP and SMX concentrations and the extent of TMP/SMX CVVHDF clearance at steady-state while the patients were still anuric and oliguric.. Data on TMP and SMX pharmacokinetics in CVVHDF are lacking and dosing recommendations are inconclusive. In both patients, CVVHDF clearance of TMP ranged from 21.5 to 28.9 mL/min, corresponding with normal renal clearance (20-80 mL/min). SMX clearance in CVVHDF showed high variability (18.7, 26.7, and 42.6 mL/min) and exceeded renal clearance values in normal renal function (1-5 mL/min). Accordingly, peak TMP serum concentrations were within the recommended range in the patient treated with a reduced TMP/SMX dose for PCP, whereas her SMX peak concentrations were only one third of recommended target concentrations.. Our data indicate that both TMP and SMX are removed by CVVHDF to a significant degree, and dose reduction of TMP/SMX in CVVHDF bears the risk of underdosing. Given variability in drug exposure in critically ill patients, therapeutic drug monitoring is advisable in anuric or oliguric patients undergoing continuous renal replacement therapy to ensure optimal TMP/SMX dosing.

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Hemodiafiltration; Humans; Infusions, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Adenine; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Fatal Outcome; Humans; Kidney Diseases; Male; Middle Aged; Multiple Organ Failure; Organophosphonates; Pneumocystis carinii; Pneumonia, Pneumocystis; Recurrence; Renal Dialysis; Tenofovir; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Renal

We report on a 3-year-old Melanesian girl admitted for acute renal failure following subfulminant hepatitis A virus infection. While the child was slowly recovering from severe cytolytic hepatitis, she presented 8 weeks of protracted fever and major eosinophilia (30,000/microl); thereafter, acute renal failure (serum creatinine 295 micromol/l) occurred. Renal histology displayed diffuse eosinophilic infiltrate, with severe acute tubulointerstitial lesions associated with mild glomerular endocapillary proliferation and eosinophilic infiltrate, suggesting an immunoallergic mechanism. The child had received cefixime and cotrimoxazole 3 weeks prior to hospitalisation for the hepatitis A virus infection. The final diagnosis was of the syndrome drug reaction with eosinophilia and systemic symptoms or DRESS, induced by cefixime or cotrimoxazole and possibly triggered by the hepatitis A virus infection.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Cefixime; Child, Preschool; Drug Therapy, Combination; Eosinophilia; Female; Hepatitis A; Humans; Kidney; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a fatal case of haemolytic uraemic syndrome in a young woman with AIDS, and disseminated adenovirus (ADV) and cytomegalovirus (CMV) co-infection. We hypothesize that ADV/CMV co-infection may have a causative role in this clinical picture.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Adenovirus Infections, Human; Colitis; Cytomegalovirus Infections; Enteritis; Fatal Outcome; Female; Foscarnet; Ganciclovir; Hemolytic-Uremic Syndrome; Humans; Respiratory Distress Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Communication Barriers; Community-Acquired Infections; Cultural Diversity; Diagnosis, Differential; Humans; Hypertension; Male; Nocardia asteroides; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

A 46-year-old morbidly obese man was admitted to the medical intensive care unit with respiratory failure. He required pressure-control ventilation and high levels of sedation with continuous-infusion lorazepam. He developed Stenotrophomonas maltophilia pneumonia; treatment included scheduled intravenous trimethoprim-sulfamethoxazole. Each of these drugs contain several hundred milligrams/milliliter of propylene glycol. On day 17 of his hospital course, 3 days after starting the trimethoprim-sulfamethoxazole, the patient developed acute renal failure consistent with acute tubular necrosis. Propylene glycol toxicity was suspected; therefore, all drugs containing propylene glycol were discontinued, and laboratory data were collected. A marked osmol gap, metabolic acidosis, and renal toxicity were attributed to both continuous and large intermittent doses of intravenous propylene glycol. Particular attention should be paid to the total amount of propylene glycol provided to patients from administered drugs. Patients in the intensive care setting who require high doses of intravenous lorazepam for sedation, as well as antimicrobial therapy with trimethoprim-sulfamethoxazole for treatment of either Stenotrophomonas maltophilia or Pneumocystis carinii pneumonia, may be at increased risk for propylene glycol toxicity and should be monitored closely.

Topics: Acute Kidney Injury; Cross Infection; Humans; Injections, Intravenous; Lorazepam; Male; Middle Aged; Pharmaceutical Solutions; Pneumocystis carinii; Pneumonia, Bacterial; Propylene Glycols; Solvents; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced hypoglycemia in a patient with acute renal failure.. English-language references identified via a MEDLINE search from January 1966 to August 1996 and a bibliographic review of pertinent articles.. Similar to sulfonylureas, sulfonamides are thought to cause hypoglycemia by increasing pancreatic secretion of insulin. To date, nine cases of TMP/SMX-induced hypoglycemia have been reported in the literature. This case represents the second report in which a patient experienced TMP/SMX-induced hypoglycemia that resolved after the dosage was adjusted for the patient's decreased renal function. This case involved a 73-year-old comatose white man initiated on high-dose TMP/SMX for nosocomial pneumonia caused by Stenotrophomonas maltophilia. After 5 days of therapy, the patient presented with severe hypoglycemia that persisted over 8 hours despite multiple intravenous bolus doses and infusions of dextrose. The patient had several risk factors that may have compounded his risk for hypoglycemia, including food deprivation and acute renal failure. After management with dextrose and dose adjustment of the patient's TMP/SMX regimen according to renal function, the hypoglycemia resolved.. TMP/SMX may cause reversible hypoglycemia that may be prolonged (approximately 12 h), particularly in patients with risk factors for hypoglycemia. Common risk factors include compromised renal function, prolonged fasting conditions, malnutrition, and the use of excessive doses. Patients with these risk factors should be monitored closely and, more importantly, initiated on a dosing regimen adjusted for renal impairment.

Topics: Acute Kidney Injury; Aged; Anti-Infective Agents; Cross Infection; Gram-Negative Bacterial Infections; Humans; Hypoglycemia; Male; Pneumonia, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

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: Acute Kidney Injury; Aged; Drug Combinations; Drug Eruptions; Humans; Kidney; Kidney Tubular Necrosis, Acute; Male; Sulfamethoxazole; Trimethoprim; 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

Bilateral kidney enlargement and renal failure are described in a five-years-old girl with brucellosis. The diagnosis was made on the basis of a rising brucella agglutination titre. Both the function and the size of the kidneys returned to normal after four weeks treatment with co-trimoxazole. Renal brucellosis may stimulate renal tuberculosis or chronic pyelonephritis and should be considered in areas where brucellosis is endemic.

Topics: Acute Kidney Injury; Brucellosis; Drug Combinations; Female; Humans; Infant; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Acute Kidney Injury; Adult; Brucellosis; Doxycycline; Drug Combinations; Humans; Male; Rhabdomyolysis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Kidney Injury; Adolescent; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Combinations; Humans; Infant; Kidney Failure, Chronic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Although acute renal failure secondary to infections is relatively common in adult patients, uremia requiring dialysis has not previously been reported in an adult patient with shigella enterocolitis. Our patient, infected with S flexneri, had severe renal failure without any evidence of sepsis, rhabdomyolysis, or the hemolytic-uremic syndrome. Antibiotic therapy with trimethoprim-sulfamethoxazole appeared to play a role in his eventual recovery.

Topics: Acute Kidney Injury; Adult; Drug Combinations; Dysentery, Bacillary; Enterocolitis, Pseudomembranous; Humans; Male; Peritoneal Dialysis; Shigella flexneri; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination