April D. Miller

Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations

Antimicrobials are the most frequently implicated class of drugs in drug‐induced seizure, with β‐lactams being the class of antimicrobials most often implicated. The seizure‐inducing potential of the carbapenem subclass may be directly related to their β‐lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, we conducted a literature search of the MEDLINE (1966—May 2010), EMBASE (1974–May 2010), and International Pharmaceutical Abstracts (1970—May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, seizure propensity of the β‐lactams is related to their binding to 7‐aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem‐cilastatin, with seizure rates ranging from 3–33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High‐dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. Although specific studies have not been conducted, data indicate that carbapenem‐associated seizure is best managed with benzodiazepines, followed by other agents that enhance GABA transmission. Due to the drug interaction between carbapenems and valproic acid, resulting in clinically significant declines in valproic acid serum concentrations, the combination should be avoided whenever possible. Clinicians should be vigilant regarding the possibility of carbapenem‐induced seizures when selecting and dosing antimicrobial therapy.

Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection

Infection with Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients, and recent surveillance data indicate that C. difficile has surpassed methicillin-resistant Staphylococcus aureus as the number one cause of hospital-acquired infections in some areas of the USA. In addition, concern over C. difficile has increased over the past decade due to the appearance of new hypervirulent strains. Metronidazole and vancomycin have remained the treatments of choice for initial therapy of primary infection with C. difficile for the past 25 years, but the persistence of spores leads to a recurrence of infection in an estimated 20-25% of patients. Patients who have one recurrent episode have up to a 65% chance of having additional recurrence. While the judicious use of antimicrobials in accordance with antibiotic stewardship guidelines remains the most effective method for the control of C. difficile, the high recurrence rate, increasing incidence, and changing epidemiology of C. difficile has led to an increased interest in the study of alternative strategies for the prevention and treatment of C. difficile disease. These alternative strategies attempt to eliminate C. difficile spores, replenish the normal gut flora, reduce the C. difficile toxin load in the bowel, or bolster the patients own immune response to the C. difficile toxins. To evaluate the available evidence on these alternative strategies, we conducted a literature search of MEDLINE (1966-March 2011) and International Pharmaceutical Abstracts (1970-March 2011). Available citations from these articles were also utilized. The aim of this review is to summarize the available evidence for alternative treatment strategies for C. difficile disease and to make recommendations for their place in therapy.

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.

Extended-Release Mesalamine Granules for Ulcerative Colitis

OBJECTIVE: To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). DATA SOURCES: Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. DATA SYNTHESIS: The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. CONCLUSIONS: Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient.

What is known and Objective:  Thermodysregula‐tion, including hypothermia, is recognized as a potential adverse effect secondary to atypical antipsychotics. We report the first known case of hypothermia possibly associated with long‐acting risperidone depot injection, precipitating further adverse events secondary to supratherapeutic phenytoin concentrations.

Topiramate: Safety and Efficacy of its Use in the Prevention and Treatment of Migraine

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramates role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports have demonstrated topiramate as a cause of cognitive and behavioural changes. The use of topiramate in migraine prevention can improve a patients quality of life and is a cost-effective option for migraine prevention.

Topiramate-induced myoclonus and psychosis during migraine prophylaxis

PURPOSE A case of topiramate-induced myoclonus and acute psychosis in a patient taking the recommended dosage of topiramate for migraine prophylaxis is reported. SUMMARY A 29-year-old Caucasian, wheelchair-bound woman with diplegic cerebral palsy and a history of migraines was admitted to the hospital after developing paranoid thoughts and episodes of myoclonus two weeks after an increase in her topiramate dosage (25 mg twice daily to 50 mg twice daily). Her physical examination upon admission was unremarkable, with the exception of a temperature of 38.2 degrees C. Diagnostic laboratory test values, including those of the cerebrospinal fluid, were within normal limits. During neurologic examination, arm jerking, lip smacking, and finger movements occurred spontaneously and unprovoked, and severe bilateral leg myoclonus with plantar stimulation was observed. The results of an ultrasound of her lower extremities and a computed tomography scan of the brain with and without contrast revealed no abnormalities. An electroencephalogram was taken and showed nothing unusual. After nonpharmacologic etiologies were ruled out, her topiramate dosage was decreased and discontinued over four days. Her mental status and myoclonus drastically improved. She was stable and discharged within 24 hours of topiramate discontinuation. Follow-up at six months revealed that her myoclonus had completely resolved. While she has experienced additional psychotic episodes, these were mild and appear to be related to her depression. Myoclonus has not returned. CONCLUSION A patient with cerebral palsy experienced myoclonus and acute psychosis after receiving a standard dosage of topiramate for migraine prophylaxis.

Medication use in bariatric surgery patients: what orthopedists need to know.

By understanding bariatric surgery procedures performed and the need for additional medication management, optimal outcomes can be achieved in these patients.

Antimicrobial prophylaxis in open lower extremity fractures

Clinical question: Based on the grade of open fracture, which antibiotic should be selected for antimicrobial prophylaxis, and what is the optimal timing and duration of administration? Results: For Grade I and II open fractures, a first-generation cephalosporin (eg, cefazolin) should be administered within 3 hours of initial injury and be continued for 24 hours after initial injury. Grade III open fractures require coverage with an aminoglycoside in addition to a first-generation cephalosporin within 3 hours of initial injury, and antibiotics should be continued for 48–72 hours after initial injury but no more than 24 hours after wound closure. If a fracture is at risk of contamination with clostridium species, such as a farm-related injury, penicillin should be added to the antibiotic regimen. Implementation: Pitfalls to avoid when using antibiotics for infection prophylaxis in open fractures include utilizing cultures immediately postinjury to direct choice of agent for antimicrobial prophylaxis, because infecting pathogens do not typically correlate to pathogens initially cultured after injury; failure to consider patients’ medication allergy history or reconcile allergy records; and failure to obtain a thorough history to determine injury exposure (eg, farm, water).

Differences in hospital glycemic control and insulin requirements in patients recovering from critical illness and those without prior critical illness

Introduction Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. Methods Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). Results Average blood glucose did not differ significantly between groups (transition group 9.49 mmol/L, direct floor group 9.6 mmol/L; P = 0.83). Significant differences in insulin requirements were observed between groups with average daily doses of 55.9 units in patients transitioning from the intensive care unit (ICU) versus 25.6 units in the direct floor group (P = 0.004). Conclusions Patients recovering from critical illness required significantly larger doses of insulin than those patients admitted directly to the floor. Managing insulin therapy in patients transitioning from the ICU may require greater insulin doses.