trimethoprim--sulfamethoxazole-drug-combination and Hypoglycemia

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 (co-trimoxazole) is a commonly used broad-spectrum antibiotic, but it can be associated with potentially serious adverse effects, often not recognized by clinicians. This is a relevant problem in elderly patients, who are particularly susceptible to adverse drug reactions. Moreover, multiple medications taken by older people increase the risk for adverse drug reactions and drug-drug interactions.. We report the case of an 85-year-old man with diabetes mellitus who attended the emergency room with severe hypoglycemia that persisted despite multiple intravenous bolus doses and continuous infusion of glucose. He needed hospital admission to stabilize glycemia. The patient, a nursing home resident, was being treated with co-trimoxazole for an uncomplicated urinary tract infection, but was also taking multiple additional drugs for his co-morbidities. After co-trimoxazole was discontinued, plasma glucose levels slowly stabilized within the normal range. A diagnosis of prolonged and refractory hypoglycemia induced mainly by the antimicrobial agent was made, with additional contribution from multiple other drugs. No further episodes of hypoglycemia occurred during the next 6 months of follow-up.. This case study illustrates once more the critical importance of prescription appropriateness in elderly patients with multiple morbidities in terms of type and dosage of drugs, in order to avoid serious adverse reactions.
.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Frail Elderly; Frailty; Humans; Hypoglycemia; Male; Polypharmacy; Risk Factors; Severity of Illness Index; Time Factors; 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: Aged; Anti-Bacterial Agents; Catheter-Related Infections; Drug Therapy, Combination; Enterococcus; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Hypoglycemia; Immunocompromised Host; Kidney Failure, Chronic; Levofloxacin; Male; Ofloxacin; Renal Dialysis; Sepsis; Stenotrophomonas maltophilia; 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

We report a case of severe hypoglycaemia following co-trimoxazole therapy. An 88-year-old woman was admitted with urinary tract infection and treated with co-trimoxazole (960 mg bid). Seven days after initiation of the treatment she became comatose. Blood sugar was 1.3 mmol/l and C-peptide at the upper limit of normal range. Glucose infusion restored normal consciousness and no hypoglycaemia recurred after interruption of co-trimoxazole therapy. Advanced aged was the only risk factor identified. Other risk factors described in previous case reports are renal failure, poor nutritional state and high doses of co-trimoxazole.

Topics: Aged; Blood Glucose; C-Peptide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemia; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Glucose homeostasis is maintained by a balance between the release and action of insulin, and the counterregulatory responses mediated principally by glucagon, catecholamines, growth hormone and cortisol. Hence, the effects of a drug on glucose metabolism may be mediated by any of these agents singly or in combination. Host factors, such as inherent glucoregulatory mechanisms, concurrent diseases, organ function and concomitant medications also increase the risk of drug-induced disturbances of glucose homeostasis in susceptible individuals. By far the most important agents causing hypoglycaemia are insulin and the sulphonylureas. Alcohol (ethanol), over-zealous glycaemic control, hypoglycaemic unawareness, detective counterregulation especially in insulin-dependent diabetes mellitus (IDDM), and renal and liver impairment are all important predisposing factors. Although antihyperglycaemic agents such as metformin and alpha-glucosidase inhibitors do not cause hypoglycaemia alone, they may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as insulin and sulphonylureas. On the other hand, the potential hypoglycaemic effects of ACE inhibitors, alpha-blockers, lipid-lowering agents and recombinant human insulin-like growth factor demonstrated in experimental settings, are of potential therapeutic interest. Iatrogenic hypoglycaemia and intensive insulin treatment are associated with hypoglycaemic unawareness which may be obviated by meticulous avoidance of hypoglycaemia. Effective patient education remains an important preventive measure. Oral glucose is used to treat mild hypoglycaemic episodes while more severe episodes are treated by intravenous glucose or glucagon. Nasal glucagon and theophylline are other experimental measures to improve recovery from hypoglycaemia. In refractory hypoglycaemia due to hyperinsulinaemia such as during sulphonylurea overdosage or quinine treatment, the long-acting somatostatin, octreotide, may suppress insulin release and restore euglycaemia. Diuretics, beta-blockers, sympathomimetics, corticosteroids and sex hormones are commonly prescribed drugs which may have adverse effects on carbohydrate metabolism especially in patients with diabetes mellitus or those who are at risk of developing glucose intolerance. Pentamidine was frequently associated with dysglycaemia due to its pancreatic beta-cell cytotoxic effects but is now used less often to treat Pneumocystis carinii pneumonia in immunosuppressed patients.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antimalarials; Aspirin; Cardiotonic Agents; Drug Interactions; Ethanol; Glucose; Gonadal Steroid Hormones; Human Growth Hormone; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Resistance; Pentamidine; Psychotropic Drugs; Sulfonylurea Compounds; Sympathomimetics; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced hypoglycemia in an immunosuppressed renal transplant patient.. English-language journal articles and reference texts identified via a MEDLINE search and a bibliographic review of pertinent data sources.. Hypoglycemia resulting from the combination of sulfonylureas and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Previously reported cases of TMP/SMX-induced hypoglycemia postulated that the sulfonamide mimics hypoglycemic sulfonylurea agents and stimulates pancreatic islet cells to secrete insulin. We report a case of hypoglycemia following the administration of high-dose TMP/SMX in a renal transplant patient. Elevated C-peptide concentrations following the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion.. Hypoglycemia has been a rarely encountered result of TMP/SMX use. Patients receiving TMP/SMX, particularly those with impaired renal function and those receiving high doses, should be monitored closely for hypoglycemia.

Topics: Adult; Humans; Hypoglycemia; Kidney Transplantation; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Combinations; Humans; Hypoglycemia; Male; Middle Aged; Multiple Myeloma; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antimicrobial agent for a wide variety of infections. It is generally well tolerated in a majority of patients; however, serious adverse effects have been described with its usage. Hypoglycaemia is an exceedingly rare but potentially life-threatening side effect of this antimicrobial agent due to its sulfonylurea-like effect. We describe a case of symptomatic, refractory hypoglycaemia secondary to TMP-SMX in a patient being treated for

Topics: Anti-Infective Agents; Glucose; Humans; Hypoglycemia; Octreotide; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Hodgkin Disease; Humans; Hypoglycemia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Both co-trimoxazole and pentamidine are used for the treatment of pneumocystis pneumonia (PCP) and are known to cause hypoglycemia as an adverse drug reaction. Here, we describe a rare case of a late-diagnosed female patient with acquired immunodeficiency syndrome (AIDS) who developed the first hypoglycemic attack as an adverse effect of co-trimoxazole, followed by a second hypoglycemic attack as an adverse effect of pentamidine. Physicians caring for patients with AIDS and PCP should be aware of possible hypoglycemia in patients with many risk factors.

Topics: Acquired Immunodeficiency Syndrome; Aged; Anti-Infective Agents; Atovaquone; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypoglycemia; Pentamidine; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 69-year-old man presented to the emergency department with lower respiratory tract infection and febrile neutropaenia. He was recently discharged following a 50-day hospital stay with newly diagnosed microscopic polyangiitis, complicated by pulmonary haemorrhage and severe renal dysfunction requiring renal replacement therapy, plasma exchange and immunosuppression (cyclophosphamide and methylprednisolone). High risk of pneumocystis pneumonia (PCP) led to an escalation in treatment from prophylactic to therapeutic oral co-trimoxazole, alongside broad-spectrum antibiotics. The patient suffered from severe and protracted hypoglycaemia, complicated by a tonic-clonic seizure 7 days after escalation to therapeutic co-trimoxazole. Endogenous hyperinsulinaemia was confirmed and was attributed to co-trimoxazole use. Hypoglycaemia resolved 48 hours after discontinuation of co-trimoxazole. PCP testing on bronchoalveolar lavage was negative. Owing to the prescription of heavy immunosuppression in patients with vasculitis and the subsequent risk of PCP warranting co-trimoxazole prophylaxis, we believe that the risk of hypoglycaemia should be highlighted.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Hypoglycemia; Male; Microscopic Polyangiitis; Piperacillin; Prednisolone; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults.. We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m. During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893).. Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.

Topics: Adult; Blood Glucose; Body Mass Index; Female; Glucose; Glucose Tolerance Test; Humans; Hypoglycemia; Male; Pre-Exposure Prophylaxis; Trimethoprim, Sulfamethoxazole Drug Combination

Coadministration of co-trimoxazole with sulfonylureas is reported to increase the risk of hypoglycemia.. We identified a cohort of Medicare beneficiaries aged 66 years or older who took glyburide or glipizide for diabetes from a 5% national sample of Medicare Part D claims data in 2008 (n = 34,239). We tracked each participant's claims during 2008-2010 for a co-trimoxazole prescription and subsequent emergency room visits for hypoglycemia. Descriptive statistics and logistic regression modeling were used to evaluate hypoglycemia-related emergency room visits after coadministration of co-trimoxazole with sulfonylureas and its utilization patterns in older adults with diabetes.. Sulfonylureas users prescribed co-trimoxazole had a significant higher risk of emergency room visits for hypoglycemia, compared with those prescribed noninteracting antibiotics (odds ratio = 3.89, 95% confidence interval = 2.29-6.60 for glipizide and odds ratio = 3.78, 95% confidence interval = 1.81-7.90 for glyburide with co-trimoxazole, using amoxicillin as the reference). Co-trimoxazole was prescribed to 16.9% of those taking glyburide or glipizide during 2008-2010, varying from 4.0% to 35.9% across U.S. hospital referral regions. Patients with polypharmacy and with more prescribers were more likely to receive co-trimoxazole. Patients with an identifiable primary care physician had 20% lower odds of receiving a co-trimoxazole prescription. Hospital referral regions with more PCPs had lower rates of coadministration of the two drugs (r = -.26, p < 0.001).. Coadministration of co-trimoxazole with sulfonylureas is associated with increased risk of hypoglycemia, compared with noninteracting antibiotics. Such coadministration is prevalent among older diabetic patients in the United States, especially in patients without an identifiable primary care physician.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Cohort Studies; Diabetes Mellitus; Drug Interactions; Emergency Service, Hospital; Female; Glipizide; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Medicare; Polypharmacy; Primary Health Care; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia.. To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug.. This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population.. We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment.. Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure.. In multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas.. Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Ciprofloxacin; Clarithromycin; Drug Interactions; Drug Prescriptions; Female; Glipizide; Glyburide; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Levofloxacin; Logistic Models; Male; Medicare; Metronidazole; Morbidity; Odds Ratio; Retrospective Studies; Risk Factors; Sulfonylurea Compounds; Texas; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Aged, 80 and over; Anti-Infective Agents; Causality; Humans; Hypoglycemia; Male; Severity of Illness Index; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

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 4-year-old boy with acute lymphoblastic leukemia who was receiving 6-mercaptopurine during the maintenance chemotherapy experienced prolonged generalized tonic nocturnal seizures because of severe hypoglycemia after his evening dose by a 12-hour period of fasting. Investigations ruled out all causes of these seizures other than the 6-mercaptopurine-induced severe hypoglycemia.

Topics: Anti-Infective Agents; Antimetabolites, Antineoplastic; Child, Preschool; Humans; Hypoglycemia; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Seizures; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of clinically significant hypoglycemia attributed to the concomitant use of trimethoprim/sulfamethoxazole (TMP/SMX) and repaglinide by a diabetic patient.. A 76-year-old diabetic patient with impaired renal function and no history of hypoglycemia was receiving treatment with repaglinide 1 mg 3 times daily. Five days after TMP/SMX therapy was started for a urinary tract infection, the man developed symptomatic hypoglycemia. Repaglinide and TMP/SMX were stopped and intravenous D-glucose was administered to normalize glucose levels. Repaglinide, but not TMP/SMX, was reintroduced 5 days later and no other hypoglycemic episode occurred. Objective causality assessments revealed that the interaction was probable (World Health Organization-Uppsala Monitoring Centre) or possible (Horn Drug Interaction Probability Scale).. This interaction between TMP/SMX and repaglinide was predictable according to available pharmacokinetic data in healthy subjects. Trimethoprim induced CYP2C8 inhibition, thus increasing the plasma concentration of repaglinide. This interaction is mentioned in the repaglinide product information. To our knowledge, however, no case of symptomatic hypoglycemia associated with a combination of repaglinide and trimethoprim has been described before. This discrepancy may be explained by the subtherapeutic dosage used in the pharmacokinetic study. Moreover, our patient had impaired renal function, which may have led to trimethoprim accumulation and potentiated its interaction with repaglinide. A direct lowering of blood glucose levels due to sulfamethoxazole, also potentiated by renal failure, could also be involved in triggering hypoglycemia.. This interaction between TMP/SMX and repaglinide may have involved inhibition of CYP2C8 by trimethoprim. Clinicians should be aware that this association may lead to symptomatic hypoglycemia, particularly in patients with renal dysfunction.

Topics: Aged; Anti-Infective Agents, Urinary; Blood Glucose; Carbamates; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Drug Interactions; Energy Intake; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Piperidines; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The objective of this study was to evaluate whether orally administered anti-infectives increase the risk of severe hypoglycemia in users of glipizide or glyburide. We performed two case-control studies and two case-crossover studies using US Medicaid data. All the anti-infectives examined were associated with an elevated risk of severe hypoglycemia. Using cephalexin as the reference category, in glipizide users, statistically significant associations were found with co-trimoxazole (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.83-5.37); clarithromycin (OR = 2.90; 95% CI: 1.69-4.98); fluconazole (OR = 2.53; 95% CI: 1.23-5.23); and levofloxacin (OR = 2.09; 95% CI: 1.35-3.25). In glyburide users, with cephalexin as the reference, statistically significant associations were found with clarithromycin (OR = 5.02; 95% CI: 3.35-7.54); levofloxacin (OR = 2.83; 95% CI: 1.73-4.62); co-trimoxazole (OR = 2.68; 95% CI: 1.59-4.52); fluconazole (OR = 2.20; 95% CI: 1.04-4.68); and ciprofloxacin (OR = 2.08; 95% CI: 1.23-3.52). In conclusion, exposure to all studied anti-infective agents were associated with subsequent severe hypoglycemia. Using cephalexin as the reference, drug-drug interactions were evident with ciprofloxacin (in glyburide users only), clarithromycin, co-trimoxazole, fluconazole, and levofloxacin.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Antifungal Agents; Aryl Hydrocarbon Hydroxylases; Blood Glucose; Case-Control Studies; Cross-Over Studies; Cytochrome P-450 CYP2C9; Drug Interactions; Enzyme Inhibitors; Ethnicity; Female; Fluconazole; Glipizide; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Risk; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

To report hypoglycaemia, a life-threatening adverse event, associated with trimethoprim-sulfamethoxazole. A sulfonylurea-like effect, leading to insulin raise, was investigated.. Two cases of trimethoprim-sulfamethoxazole-associated hypoglycaemia in 2 patients with a diagnosis of new HIV-1-infection presenting with Pneumocystis jiroveci pneumonia are reported. The patients had no predisposing factors, such as renal or liver impairment, interfering with trimethoprim-sulfamethoxazole elimination, thus leading to hypoglycaemia. Insulin plasma levels were measured in both patients.. Severe hypoglycaemia was associated with increased serum levels of insulin up to 84 microU/ml (normal values < 10 microU/ml). Continuous dextrose infusion was necessary, further suggesting the sulfonylurea-like effect of sulfamethoxazole. Interestingly, plasma levels of insulin progressively raised after trimethoprim-sulfamethoxazole administration.. Only 18 cases of trimethoprim-sulfamethoxazole associated hypoglycaemia are reported in the literature. Hypoglycaemia is a life-threatening condition, likely underreported, to consider when trimethoprim-sulfamethoxazole administration is required, even in the absence of predisposing factors or other hypoglycaemic agents. Physician should bear in mind the potential trimethoprim-sulfamethoxazole-associated adverse event especially when prolonged treatments and elevated dosage are used.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Blood Glucose; Female; Glucose; Humans; Hypoglycemia; Insulin; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4.5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (>12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction.

Topics: Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antifungal Agents; Female; Glucose; Humans; Hypoglycemia; Infant; Insulin; Male; Middle Aged; Pneumonia, Pneumocystis; Risk Factors; Seizures; 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

Hyperinsulinemic hypoglycemia associated with trimethoprim-sulfamethoxazole (TMP-SMX) has generally been reported in adults who had renal impairment or in patients with AIDS using high dose TMP-SMX. We present a 5 month-old infant with immunodeficiency due to major histocompatibility complex class II expression defect, developing hypoglycemic convulsion on the third day of high dose TMP-SMX administration. High insulin and C-peptide levels were documented at the time of hypoglycemia. To overcome hypoglycemia while TMP-SMX tapered off, diazoxide was administered which resolved hypoglycemia in 2 months.

Topics: Blood Glucose; C-Peptide; Diazoxide; Drug Administration Schedule; Female; Gene Expression; Genes, MHC Class II; Glucose; Histocompatibility Antigens Class II; Hospitalization; Humans; Hyperinsulinism; Hypoglycemia; Immunologic Deficiency Syndromes; Infant; Infusions, Intravenous; Pneumonia; Seizures; Time Factors; Treatment Outcome; 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

To assess the prevalence, presentation, and risk factors of pentamidine-induced dysglycemia.. Blood glucose values were screened in 244 consecutive immunocompromised patients with Pneumocystis carinii pneumonia: 116 being treated with cotrimoxazole and 128 others with pentamidine.. Two cotrimoxazole patients developed diabetes as a result of necrotizing pancreatitis (1.7%); the others remained euglycemic. Forty-eight pentamidine-treated patients (38.5%) developed severe glucose homeostasis disorders: hypoglycemia in 7, hypoglycemia and then diabetes in 18, and diabetes alone in 23 (P < 0.001 vs. the cotrimoxazole group). Hypoglycemia was early, sudden, often recurrent, and life-threatening, associated with inappropriately high insulin levels in plasma; the B-cell response to stimuli was poor. Of the 41 diabetic patients, 26 required insulin therapy; their plasma C-peptide levels were lower than normal, and the B-cell secretory responses to stimuli were poor. Islet cell antibodies, insulin antibodies, and insulitis were not detected. The pentamidine-treated dysglycemic patients differed from their euglycemic counterparts by higher pentamidine doses (P < 0.001), higher plasma creatinine levels (P < 0.001), and more severe anoxia (P < 0.05) and shock (P < 0.001). Most of them had received pentamidine mesylate parenterally (n = 36; 75%); six others received the isethionate salt and six exclusively pentamidine aerosols.. Pentamidine-induced dysglycemic accidents are primarily due to inappropriate insulin release and toxicity to the islet B-cells. Drug accumulation due to excessive doses, iterative courses, and/or renal impairment is the determining risk factor.

Topics: Adult; AIDS-Related Opportunistic Infections; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hypoglycemia; Infusions, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Radioimmunoassay; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMZ) and pentamidine are both licensed for the treatment of Pneumocystis carinii pneumonia (PCP). However, their use is associated with various adverse side effects. In this prospective study, 26 AIDS patients with 32 episodes of PCP were treated with pentamidine (4 mg/kg/d). Each patient was treated for 12 to 21 days, depending on the rapidity of onset of the clinical response. During the 32 PCP episodes, hypoglycemia occurred in 16 instances, azotemia in 12, liver toxicity in 10, and leukopenia in 8. The occurrence of thrombopenia, leukopenia, and liver toxicity was not related to age, pentamidine levels, or other complications. However, patients who had hypoglycemia during pentamidine treatment had higher serum pentamidine levels than patients who did not have hypoglycemia (107 +/- 40 versus 70 +/- 26 ng/ml, p less than 0.004). In addition, we observed that patients with azotemia showed higher pentamidine levels during treatment (120 +/- 35 versus 64 +/- 22 ng/ml, p less than 0.001). In fact, 100% (11/11) of patients with serum pentamidine concentration greater than 100 ng/ml had fasting hypoglycemia and/or azotemia, while 33% (7/21) of those with pentamidine levels less than 100 ng/ml had these side effects (p less than 0.001). The relative risk of these complications with pentamidine levels greater than 100 ng/ml was 3 (95% confidence interval, 1.6 to 5.5). Fine-tuning the dose of pentamidine may eventually prove useful to avoid toxicity and optimize therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Analysis of Variance; Chi-Square Distribution; Female; Humans; Hypoglycemia; Male; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Quebec; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Uremia

Topics: Blood Glucose; Bronchitis; Cough; Humans; Hypoglycemia; Pharyngitis; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfonamides have been reported to augment the hypoglycemic effects of chlorpropamide, glyburide, and tolbutamide. This case report is the first to describe a possible interaction with glipizide. An 83-year-old man receiving glipizide 10 mg bid developed symptomatic hypoglycemia within three days of adding trimethoprim/sulfamethoxazole (TMP/SMX) to his regimen. All other factors, including laboratory data, dietary intake, activity level, and concurrent use of other medications, were stable and noncontributory. This patient may have been at increased risk for this interaction secondary to his age and history of alcohol abuse. The mechanism of the interaction is probably inhibition of glipizide metabolism rather than protein-binding displacement. This case suggests that, when TMP/SMX is combined with glipizide, patients should be closely monitored, especially those at high risk for hypoglycemia.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Interactions; Glipizide; Humans; Hypoglycemia; Male; Sulfonylurea Compounds; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Drug Combinations; Humans; Hypoglycemia; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Drug Combinations; Humans; Hypoglycemia; Kidney Failure, Chronic; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfonylureas hypoglycemic action may be potentiated by sulfonamides. This case report describes a 69-year-old female with a hypoglycemic episode suggestive of an interaction between chlorpropamide and sulfamethoxazole (co-trimoxazole). The patient had no renal or liver dysfunction. This interaction is rare but one should be aware of it, especially with combination products.

Topics: Aged; Blood Glucose; Chlorpropamide; Drug Combinations; Female; Humans; Hypoglycemia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Drug Combinations; Humans; Hypoglycemia; Immunologic Deficiency Syndromes; Male; Pentamidine; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Chlorpropamide; Drug Combinations; Drug Synergism; Female; Humans; Hypoglycemia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination