Euglycemic Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter Type 2 Inhibitors in Patients With Type 2 Diabetes Mellitus Receiving Oral Therapy.

INTRODUCTION AND OBJECTIVE: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. CASE REPORTS: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. DISCUSSION: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. CONCLUSION: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.

Luminal Toxin-Binding Agents for Clostridium difficile Infection.

OBJECTIVE: To systematically search the literature for trials evaluating luminal toxin-binding agents (LTBAs) for Clostridium difficile infection (CDI). METHODS: A systematic search was conducted utilizing PubMed and International Pharmaceutical Abstracts with the following terms: anion-exchange resins, C difficile, cholestyramine, tolevamer, and colestipol. Articles were included if published in the English language and reported clinical outcomes of more than 5 adult humans with CDI treated with LTBAs. RESULTS: Nearly all clinical trials evaluated LTBA as monotherapy for CDI and LTBAs are inferior to standard therapy. In contemporary practice, LTBAs are employed as adjunctive or sequential therapy for which there is a paucity of data. Some data suggest potential efficacy for recurrent CDI. Current guidelines for CDI assert LTBAs are contraindicated due to drug-drug interactions with vancomycin. However, the impact of this interaction on clinical outcomes has not been evaluated, and it is unknown whether higher doses of vancomycin or separating the administration of LTBAs from vancomycin would mitigate this interaction. CONCLUSION: LTBA monotherapy is inferior to vancomycin and metronidazole for CDI. Some data indicate possible benefit in reducing recurrent CDI, but outcomes with adjunctive and/or sequential LTBAs are unavailable. Further studies are needed to investigate the role of LTBAs for CDI.

Antimicrobial treatment of asymptomatic bacteriuria in noncatheterized adults: a systematic review.

Asymptomatic bacteriuria (ASB) is a common clinical finding characterized by the presence of bacteria in the urine of an individual without signs or symptoms suggestive of urinary tract infection. Despite available guidelines on the diagnosis and management of ASB, it is often managed inappropriately. We performed a systematic review of clinical trials evaluating antimicrobial therapy for ASB, identified translational barriers to evidence-based practice, and we offer strategies to optimize antimicrobial use for ASB. We conducted a systematic search of the PubMed, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health databases, and the Cochrane Library. Randomized controlled trials, cohort trials, case-control studies, and meta-analyses published in the English language were included in this review if they addressed treatment of ASB with at least one antimicrobial agent in nonpregnant adults. Articles were excluded if they evaluated patients with indwelling urinary catheters or were not clinical trials. Of the 304 articles identified from the search, 287 were excluded; thus 17 articles met the inclusion criteria. Although treatment of ASB with antimicrobial therapy may improve short-term microbiologic outcomes, the clinical significance is diminished because the effect is not sustained, there is no measurable improvement in morbidity or mortality, and some data indicate that therapy is deleterious. Several translational barriers that preclude adoption of evidence-based practice are identified. Treatment guidelines may not achieve their desired effect and underscore the need for additional methods to translate clinical trial data into practice. Clinical pharmacists are a core member of the antimicrobial stewardship team and in an important position to participate in initiatives that promote appropriate antimicrobial use. We suggest a multifaceted approach consisting of education and frequent routine prospective audits with feedback coupled with appropriate process and outcome measures.

Antithrombotics in heart failure with reduced ejection fraction and normal sinus rhythm: an evidence appraisal.

OBJECTIVE: To review the thromboembolic risk, pathophysiology associated with the risk, and literature investigating the use of antithrombotics in patients with heart failure with reduced ejection fraction and normal sinus rhythm (HFrEF-NSR). DATA SOURCES: An English language literature search was performed with MEDLINE/PubMed and Embase from January 1950 to October 2013 using the search terms heart failure, HFrEF, systolic heart failure, cardiomyopathy, left ventricular dysfunction, sinus rhythm, thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, acute coronary events, coronary artery disease, stroke, and cerebrovascular events to identify relevant articles. References in the retrieved articles were also assessed to identify other important articles. STUDY SELECTION AND DATA ABSTRACTION: All pertinent original studies, reviews, consensus documents, and guidelines were evaluated for inclusion. DATA SYNTHESIS: Patients with HFrEF-NSR may be predisposed to developing thromboembolic events. Studies that have examined the role of antithrombotics (warfarin and/or antiplatelet therapy) for reducing thromboembolic risk have been inconclusive. The WASH and HELAS pilot trials--the only studies with a no-antithrombotics or placebo comparator group--did not find a benefit with antithrombotic therapy but found an increased risk of bleeding with warfarin and of hospitalizations with aspirin. Although the clinical outcome studies (WATCH and WARCEF) suggested that warfarin may reduce stroke risk compared with antiplatelet therapy, the lack of a placebo group and lower-than-projected enrollment prevents definitive conclusions from being made. CONCLUSIONS: Current evidence does not support the routine use of antithrombotics for preventing thromboembolic events in patients with HFrEF-NSR without compelling indications.

Review of insulin therapy and pen use in hospitalized patients.

OBJECTIVE: Hyperglycemia is common among hospitalized patients, affecting approximately 40% of patients at the time of hospital admission, despite the fact that 1 in every 8 patients has no previous diagnosis of diabetes. Hyperglycemia has been associated with poor patient outcomes, including higher rates of morbidity and mortality across a range of conditions. This review discusses options for the effective management of hyperglycemia with a focus on the use of disposable insulin pens in the hospital. METHODS: Literature, including guidelines for hospital management of hyperglycemia, and information regarding methods of insulin administration were reviewed. RESULTS: Appropriate glucose control via administration of insulin within hospitals has been acknowledged as an important goal and is consistent with achieving patient safety. Insulin may be administered subcutaneously using a pen or vial and syringe or infused intravenously. Levels of patient and provider satisfaction are higher with pen administration than with vial and syringe. Insulin pens have many safety and convenience features including enhanced dose accuracy and autocover/autoshield pen needles. CONCLUSION: Use of insulin pens instead of vials and syringes can provide several advantages for hospitalized patients, including greater satisfaction among them and health care providers, improved safety, and reduced costs. These advantages can continue following patient discharge.