Use of Psychostimulants in Patients with Dementia (October).

Ann Pharmacother. 2010 Aug 24;

Authors: Dolder CR, Davis LN, McKinsey J

OBJECTIVE: To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia. DATA SOURCES: Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed. STUDY SELECTION AND DATA EXTRACTION: All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate. DATA SYNTHESIS: Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities. CONCLUSIONS: Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.

PMID: 20736422 [PubMed - as supplied by publisher]

[Read more →]

Treatment of Recurrent Stenotrophomonas maltophilia Ventilator-Associated Pneumonia with Doxycycline and Aerosolized Colistin (October).

Ann Pharmacother. 2010 Aug 24;

Authors: Wood GC, Underwood EL, Croce MA, Swanson JM, Fabian TC

OBJECTIVE: To report a case of recurrent Stenotrophomonas maltophilia ventilator-associated pneumonia (VAP) that was successfully treated with doxycycline and aerosolized colistin. CASE SUMMARY: A 28-year-old male was admitted with a severe head injury and required mechanical ventilation. The patient developed S. maltophilia VAP on hospital day 17, which was cured after 7 days of treatment with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). However, on day 34, the patient developed recurrent S. maltophilia VAP that did not respond clinically or demonstrate eradication on follow-up culture after 10 days of TMP/SMX. At that time, TMP/SMX was discontinued and treatment was initiated with intravenous doxycycline and aerosolized colistin. The VAP episode was cured after 14 days of treatment with doxycycline/aerosolized colistin. DISCUSSION: S. maltophilia is an emerging cause of VAP in some centers. This organism is associated with high mortality rates and has few treatment options because it is intrinsically resistant to most drug classes. Recent data suggest that doxycycline and aerosolized colistin each are effective in treatment of other multidrug-resistant organisms, such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, this is the first report describing the use of this antibiotic regimen for S. maltophilia. High-dose TMP/SMX is considered to be the drug of choice primarily based on excellent in vitro activity. Few data exist on how to treat patients who fail therapy with TMP/SMX or cannot receive that drug because of resistance, allergy, or adverse events. Thus, it is important to report alternative methods for treating this infection. CONCLUSIONS: The positive clinical response to doxycycline and aerosolized colistin seen in the patient described here suggests that this combination may be an alternative treatment in patients who fail initial treatment or cannot receive standard therapies.

PMID: 20736426 [PubMed - as supplied by publisher]

[Read more →]

Alternate-Day Statin Therapy for the Treatment of Hyperlipidemia (September).

Ann Pharmacother. 2010 Aug 11;

Authors: Reindl EK, Wright BM, Wargo KA

OBJECTIVE: To evaluate the safety, efficacy, and cost of alternate-day statin therapy in the treatment of hyperlipidemia. DATA SOURCES: Systematic searches were conducted for primary literature sources involving alternative statin regimens using PubMed, EMBASE, Google Scholar, and International Pharmaceutical Abstracts (January 1966-March 2010). Articles selected were limited to those published in the English language. Reference citations from relevant publications identified were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified were reviewed and 17 trials (14 prospective and 3 retrospective) involving alternate-day statin dosing were included. Studies involving alternative statin dosing regimens other than alternating days were excluded from this review. DATA SYNTHESIS: Daily administration of statins is the standard of therapy used to reduce low-density lipoprotein cholesterol (LDL-C) levels as well as atherosclerosis that may lead to coronary events. Through LDL-C lowering and pleiotropic effects, statins decrease cardiovascular morbidity and mortality. Unfortunately, due to cost and adverse effects of statins, some patients are nonadherent to statin therapy. Several small studies have found alternate-day statin therapy to be as effective at reducing LDL-C as daily administration, while also lowering the incidence of adverse reactions and potentially lowering cost. CONCLUSIONS: Alternate-day statin therapy may decrease cost and therapy limiting adverse reactions while potentially increasing regimen adherence and positively affecting the lipid panel. Further research is needed to determine whether this alternative regimen produces similar cardiovascular outcomes as those with daily statin therapy.

PMID: 20702760 [PubMed - as supplied by publisher]

[Read more →]

Related Articles

The relationship between inpatient fluoroquinolone use and Clostridium difficile-associated diarrhea.

Ann Pharmacother. 2010 May;44(5):826-31

Authors: Novell MJ, Morreale CA

BACKGROUND: Limited evidence suggests there may be a link between fluoroquinolone use and Clostridium difficile-associated diarrhea (CDAD), but such an association remains unclear due to conflicting data. OBJECTIVE: To determine the relationship between inpatient fluoroquinolone use and CDAD; secondary objectives included the relationship between CDAD and fluoroquinolone selection, duration of therapy, and route of administration, as well as the association between fluoroquinolones and CDAD complications. METHODS: We conducted a retrospective, case-control study of adult inpatients diagnosed with CDAD during the period of July 2007-July 2008. In total, 174 case patients were matched on a 1:1 basis with controls. A thorough assessment of all inpatient antibiotic use was conducted, including regimens administered at our institution within the previous 8 weeks. Odds ratios were calculated using univariate logistic-regression analysis. RESULTS: Use of fluoroquinolones was not significantly different between patients with CDAD and matching controls (OR 1.36; 95% CI 0.09 to 2.10; p = 0.16). No relationship was found between CDAD and the individual fluoroquinolones: ciprofloxacin (OR 1.36; 95% CI 0.87 to 2.12; p = 0.18), levofloxacin (OR 1.17; 95% CI 0.62 to 2.22; p = 0.63), and moxifloxacin (OR 1.34; 95% CI 0.81 to 2.20; p = 0.25). Fluoroquinolone route of administration did not differ significantly between groups for patients receiving intravenous (OR 1.20; 95% CI 0.74 to 1.94; p = 0.46) or oral (OR 0.79; 95% CI 0.44 to 1.44; p = 0.45) therapy. Complications from CDAD were not significantly increased by fluoroquinolone use (OR 1.37; 95% CI 0.72 to 2.61; p = 0.35). CONCLUSIONS: Inpatient administration of fluoroquinolones was not associated with CDAD at our institution. Fluoroquinolone use in patients who developed CDAD was not related to higher incidences of CDAD-related complications.

PMID: 20354161 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Hypokalemia following polyethylene glycol-based bowel preparation for colonoscopy in older hospitalized patients with significant comorbidities.

Ann Pharmacother. 2010 Mar;44(3):466-70

Authors: Ho JM, Juurlink DN, Cavalcanti RB

BACKGROUND: Polyethylene glycol-based bowel preparations (PEGBPs) are widely perceived as safe and effective alternatives to oral sodium phosphate for bowel cleansing prior to colonoscopy. Most studies supporting this belief involve young patients with few comorbidities. OBJECTIVE: To characterize the incidence of electrolyte disturbances following PEGBPs administered prior to colonoscopy among elderly inpatients and hypothesize that PEGBP would be associated with hypokalemia in this setting. METHODS: This retrospective chart review, conducted at 3 tertiary care teaching hospitals in Toronto, Canada, from 2005 to 2007, included 96 consecutive patients aged 65 or older who were admitted to the hospital and given PEGBP prior to their first inpatient colonoscopy. Patients were excluded if they received additional cathartics, underwent colonoscopy while admitted to a critical care unit, or were admitted for a complication arising from an outpatient colonoscopy. The primary outcome was hypokalemia (serum potassium < or =3.2 mEq/L) within 48 hours of PEGBP. RESULTS: Of 96 patients, 73 had serum electrolytes measured at baseline and within 48 hours following PEGBP administration. Hypokalemia was identified in 4 patients (5.5%) prior to PEGBP and in 15 patients (20.5%) after PEGBP (p < 0.001). The incidence of significant hypokalemia, defined as serum potassium < or =3.0 mEq/L, in this group was 9.6% (p = 0.008). We found consistent results among patients with and without concomitant diuretic treatment. CONCLUSIONS: Among older patients, administration of PEGBP is commonly complicated by the development of hypokalemia, which is occasionally severe. Monitoring of electrolytes may be necessary following colonoscopy, particularly in patients with cardiac or renal disease.

PMID: 20124467 [PubMed - indexed for MEDLINE]

[Read more →]

Inappropriate Prescribing Predicts Adverse Drug Events in Older Adults(June).

Ann Pharmacother. 2010 May 11;

Authors: Lund BC, Carnahan RM, Egge JA, Chrischilles EA, Kaboli PJ

BACKGROUND: Explicit measures of potentially inappropriate prescribing, such as the Beers criteria, have been associated with risk for adverse drug events (ADEs). However, no such link has been established for actual inappropriate prescribing using implicit measures. OBJECTIVE: To determine whether an implicit measure of inappropriate prescribing can predict ADE risk. METHODS: Patients were veterans aged 65 years and older who were seen in primary care clinics and participated in a randomized controlled trial of a pharmacist-physician collaborative intervention. Inappropriate prescribing was determined at baseline, using the 2003 Beers criteria as an explicit measure and the Medication Appropriateness Index (MAI) as an implicit measure. A modified MAI scoring approach was designed to target ADE risk and was used in addition to standard scoring. ADEs that occurred during the 3 months following baseline were assessed by patient interview and plausibility verification by blinded pharmacist review. Logistic regression analysis was used to determine whether inappropriate prescribing predicted risk for an ADE, controlling for potential confounding factors. RESULTS: Of 236 patients, 34 (14.4%) experienced an ADE. Inappropriate prescribing was common at baseline, with 48.7% of patients receiving a Beers criteria drug and 98.7% of patients having an inappropriate rating on at least 1 MAI criterion. Modified MAI scoring, but not other measures of inappropriate prescribing, significantly predicted ADE risk. For every unit increase in modified MAI score (3.1 +/- 3.5; mean +/- SD), the adjusted 3-month odds of an ADE increased 13% (OR 1.13; 95% CI 1.02 to 1.26). For example, patients with a modified MAI score of 3, near the precise mean score of 3.1, were at a nearly 40% greater risk for an ADE compared with patients with a score of zero. CONCLUSIONS: Implicit measurement of actual inappropriate prescribing predicted ADE risk, an important clinical outcome. This finding helps confirm the validity of prior studies that have relied on explicit measures to link potentially inappropriate prescribing to adverse health outcomes.

PMID: 20460558 [PubMed - as supplied by publisher]

[Read more →]

Eltrombopag: A Novel Oral Thrombopoietin Receptor Agonist (June) (CE).

Ann Pharmacother. 2010 May 11;

Authors: Corman SL, Mohammad RA

OBJECTIVE: To review the pharmacology and pharmacokinetics and evaluate the safety and efficacy of eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenia associated with hepatitis C virus (HCV) cirrhosis. DATA SOURCES: A Cochrane Controlled Trial Register, clinicaltrials.gov, EMBASE, and MEDLINE search was performed (January 1966-March 2010) using the key terms eltrombopag and SB-497115-GR. Searches were limited to published English-language studies in humans and a reference review of the pertinent literature was conducted. STUDY SELECTION AND DATA EXTRACTION: Published pharmacokinetic data and safety and efficacy trials, case reports, and case series on the use of eltrombopag were selected for inclusion. DATA SYNTHESIS: Eltrombopag is a novel second-generation thrombopoietin receptor agonist that was approved by the Food and Drug Administration for the treatment of chronic ITP in patients who had an insufficient response to corticosteroids, intravenous immune globulin, or splenectomy. Eltrombopag has been shown to be superior to placebo in increasing platelet counts, with more patients achieving counts >50 x 10(3)/muL. One study has also shown eltrombopag to be effective in the treatment of thrombocytopenia associated with HCV cirrhosis. Eltrombopag has a boxed warning related to risk of hepatotoxicity, with criteria for discontinuation in patients with elevated liver enzyme levels or clinical signs of liver damage. As such, close monitoring of laboratory parameters is required, and patients must be registered with the PROMACTA CARES program. CONCLUSIONS: Eltrombopag is effective in increasing platelet counts in patients with chronic ITP and in patients with HCV cirrhosis. In the treatment of ITP, eltrombopag has been studied only for short durations and is more expensive than first-line oral corticosteroids; therefore, it should be considered a second-line agent. More studies are needed to identify a place in therapy for eltrombopag in the treatment of thrombocytopenia associated with HCV cirrhosis.

PMID: 20460556 [PubMed - as supplied by publisher]

[Read more →]

Saxagliptin: A New Dipeptidyl Peptidase 4 Inhibitor for Type 2 Diabetes (June) (CE).

Ann Pharmacother. 2010 May 11;

Authors: Borja-Hart NL, Whalen KL

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of saxagliptin, a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes. DATA SOURCES: Searches of PubMed (1966-March 2010) and International Pharmacy Abstracts (1970-March 2010) were conducted using the key words saxagliptin, Onglyza, and BMS-477118. A review of bibliographies of retrieved articles was also performed to identify additional references. STUDY SELECTION AND DATA EXTRACTION: All identified studies published in English and involving efficacy and safety of saxagliptin in the treatment of type 2 diabetes were reviewed. DATA SYNTHESIS: Saxagliptin is a competitive inhibitor of DPP-4 that slows the degradation of incretin hormones, thereby stimulating insulin secretion, reducing postprandial glucagon, and decreasing glucose levels. Saxagliptin is well absorbed after oral administration and demonstrates a pharmacokinetic profile that is compatible with once-daily dosing. Clinical trials with saxagliptin monotherapy for the treatment of type 2 diabetes showed a reduction in hemoglobin A1c (A1C) of 0.43-0.9%. Saxagliptin has demonstrated similar reductions in A1C when used as add-on therapy with metformin, sulfonylureas, and thiazolidinediones. The combination of saxagliptin and metformin for initial therapy in treatment-naïve patients was associated with greater improvements in A1C than either agent alone. In general, saxagliptin therapy is well tolerated. The most common adverse effects occurring in clinical trials were headache, nasopharyngitis, upper respiratory tract infections, and urinary tract infections. CONCLUSIONS: Saxagliptin is effective as monotherapy or add-on therapy for the management of type 2 diabetes. Because saxagliptin has a higher cost and reduces A1C and other surrogate markers of glucose control to a lesser extent than other well-validated therapies, such as metformin, saxagliptin should be reserved for patients who fail or are intolerant of conventional treatments for type 2 diabetes.

PMID: 20460554 [PubMed - as supplied by publisher]

[Read more →]

Evaluation of Aminoglycoside Clearance Using the Modification of Diet in Renal Disease Equation Versus the Cockcroft-Gault Equation as a Marker of Glomerular Filtration Rate(June).

Ann Pharmacother. 2010 Apr 27;

Authors: Ryzner KL

BACKGROUND: Accurate estimation of kidney function is essential for safe administration of renally cleared drugs. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault (CG) equation as an estimation of glomerular filtration rate. Few data exist regarding the utility of the Modification of Diet in Renal Disease (MDRD) equation in drug dosing. OBJECTIVE: To evaluate glomerular filtration rate based on creatinine clearance (CrC1) derived from the MDRD or the CG equation compared with patient-specific CrCl calculated from aminoglycoside peak and trough concentrations. METHODS: Medical records of patients who received aminoglycoside antibiotics were reviewed over 1 year. Patients who received aminoglycosides via conventional dosing with peak and trough concentrations at steady state were included. Calculations based on standard pharmacokinetic equations were used to estimate CrCl from aminoglycoside serum concentrations. Patient-specific CrCl estimated from aminoglycoside concentrations was compared with estimated CrCl from the CG or MDRD equation. RESULTS: Fifty-five patients were included in the final analysis. The primary outcome showed concordance between estimated and actual aminoglycoside clearance was 0.53 (95% CI 0.18 to 0.88) for the CG equation and 0.41 (95% CI 0.04 to 0.78) for the MDRD equation. Subgroup analysis also favored CG as a better predictor of CrCl. This signified a stronger correlation between the CG equation and aminoglycoside clearance. CONCLUSIONS: Compared with the MDRD equation, the CG equation provided better correlation of estimated glomerular filtration rate for aminoglycoside antibiotics. Institutions should continue to use the CG equation as the standard of practice to safely adjust aminoglycoside doses in patients with renal dysfunction.

PMID: 20424182 [PubMed - as supplied by publisher]

[Read more →]

Use of Information Technology in Medication Reconciliation: A Scoping Review (May).

Ann Pharmacother. 2010 Apr 6;

Authors: Bassi J, Lau F, Bardal S

OBJECTIVE: To identify studies involving information technology (IT) in medication reconciliation (MedRec) and determine how IT is used to facilitate the MedRec process. DATA SOURCES: The search strategy included a database search of MEDLINE and Cumulative Index of Nursing and Allied Health Literature (CINAHL), hand-searching of collected material, and references from articles retrieved. The database search was limited to English-language papers. MEDLINE includes publications dating back to 1950 and CINAHL includes those dating back to 1982. The search included articles in both databases up to March 2009. Boolean queries were constructed using combinations of search terms for medication reconciliation, IT, and electronic records. STUDY SELECTION AND DATA EXTRACTION: Three inclusion criteria were used. The study had to (1) involve the MedRec process, (2) be a primary study, and (3) involve the use of IT. Selection was performed by 2 reviewers through consensus. Data related to study characteristics, focus, and IT use were extracted. DATA SYNTHESIS: The included studies described a range of IT used throughout the MedRec process, from basic email and databases to specialized MedRec tools. A generic MedRec workflow was created and types of IT found in the studies were mapped to the workflow activities as well as to a set of functionalities based on the Institute of Medicine’s Key Capabilities of an Electronic Health Record System. In the studies reviewed, IT was mainly used to obtain medication information. Although there were only a few MedRec tools in the studies, those that did exist supported the central activities for MedRec: comparison of medications and clarification of discrepancies. CONCLUSIONS: MedRec is an important process to ensure patient medication safety. Evidence was found that IT can and has been used to facilitate some MedRec activities and new applications are being developed to support the entire MedRec process.

PMID: 20371752 [PubMed - as supplied by publisher]

[Read more →]

High-Dose Continuous Infusion {beta}-Lactam Antibiotics for the Treatment of Resistant Pseudomonas aeruginosa Infections in Immunocompromised Patients (May).

Ann Pharmacother. 2010 Apr 6;

Authors: Moriyama B, Henning SA, Childs R, Holland SM, Anderson VL, Morris JC, Wilson WH, Drusano GL, Walsh TJ

OBJECTIVE: To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. CASE SUMMARY: Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. DISCUSSION: Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. CONCLUSIONS: Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.

PMID: 20371747 [PubMed - as supplied by publisher]

[Read more →]

The Relationship Between Inpatient Fluoroquinolone Use and Clostridium difficile-Associated Diarrhea(May).

Ann Pharmacother. 2010 Mar 30;

Authors: Novell MJ, Morreale CA

BACKGROUND: Limited evidence suggests there may be a link between fluoroquinolone use and Clostridium difficile-associated diarrhea (CDAD), but such an association remains unclear due to conflicting data. OBJECTIVE: To determine the relationship between inpatient fluoroquinolone use and CDAD; secondary objectives included the relationship between CDAD and fluoroquinolone selection, duration of therapy, and route of administration, as well as the association between fluoroquinolones and CDAD complications. METHODS: We conducted a retrospective, case-control study of adult inpatients diagnosed with CDAD during the period of July 2007-July 2008. In total, 174 case patients were matched on a 1:1 basis with controls. A thorough assessment of all inpatient antibiotic use was conducted, including regimens administered at our institution within the previous 8 weeks. Odds ratios were calculated using univariate logistic-regression analysis. RESULTS: Use of fluoroquinolones was not significantly different between patients with CDAD and matching controls (OR 1.36; 95% CI 0.09 to 2.10; p = 0.16). No relationship was found between CDAD and the individual fluoroquinolones: ciprofloxacin (OR 1.36; 95% CI 0.87 to 2.12; p = 0.18), levofloxacin (OR 1.17; 95% CI 0.62 to 2.22; p = 0.63), and moxifloxacin (OR 1.34; 95% CI 0.81 to 2.20; p = 0.25). Fluoroquinolone route of administration did not differ significantly between groups for patients receiving intravenous (OR 1.20; 95% CI 0.74 to 1.94; p = 0.46) or oral (OR 0.79; 95% CI 0.44 to 1.44; p = 0.45) therapy. Complications from CDAD were not significantly increased by fluoroquinolone use (OR 1.37; 95% CI 0.72 to 2.61; p = 0.35). CONCLUSIONS: Inpatient administration of fluoroquinolones was not associated with CDAD at our institution. Fluoroquinolone use in patients who developed CDAD was not related to higher incidences of CDAD-related complications.

PMID: 20354161 [PubMed - as supplied by publisher]

[Read more →]

Successful Treatment of Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Bacteremia with the Addition of Rifampin to Daptomycin (May).

Ann Pharmacother. 2010 Mar 30;

Authors: Ahmad NM, Rojtman AD

OBJECTIVE: To report a case in which daptomycin-nonsusceptible methicillinresistant Staphylococcus aureus (MRSA) bacteremia was successfully treated with the addition of rifampin to daptomycin. CASE SUMMARY: An 84-year-old male presented with fever and chills following cystoscopy. After culturing was conducted, the patient received single doses of vancomycin and gentamicin and then continued on vancomycin plus ceftazidime. Blood cultures grew MRSA, with vancomycin and daptomycin minimum inhibitory concentrations (MICs) of </=1 mug/mL and 0.25 microg/mL, respectively. Vancomycin was continued, with trough concentrations maintained >15 microg/mL, but results of blood cultures remained positive. On day 10, therapy was switched to daptomycin 6 mg/kg/day, but culture results remained positive. On day 13, testing for vancomycin heteroresistance was negative, with the MIC unchanged. The vancomycin MIC remained unchanged on day 19, but the daptomycin MIC had increased to 2 microg/mL. Rifampin 300 mg orally twice daily was added on day 20; blood cultures obtained 2 days later were sterile. The patient was discharged to complete a 6-week course of antibiotics and was doing well 4 months following therapy. DISCUSSION: Analysis of MRSA isolates obtained on days 1 and 19 showed an increase in the daptomycin MIC from 0.25 to 2 microg/mL. Because intervening isolates were not available for susceptibility testing, it is not possible to associate this increase with exposure to either vancomycin or daptomycin. Although in vitro synergy was not seen in this case, addition of rifampin to daptomycin therapy resolved the bacteremia. CONCLUSIONS: In patients with persistent MRSA bacteremia, isolates should be retested for susceptibility to both daptomycin and vancomycin, including assessment for vancomycin heteroresistance. Addition of rifampin to daptomycin may be effective for persistent MRSA bacteremia, even if daptomycin MICs are elevated. Prospective studies are needed to define the role of combination therapy.

PMID: 20354160 [PubMed - as supplied by publisher]

[Read more →]

Adverse Drug Events in Adult Patients Leading to Emergency Department Visits(April).

Ann Pharmacother. 2010 Mar 16;

Authors: Sikdar KC, Alaghehbandan R, Macdonald D, Barrett B, Collins KD, Donnan J, Gadag V

BACKGROUND: Adverse drug events (ADEs) occurring in the community and treated in emergency departments (EDs) have not been well studied. OBJECTIVE: To determine the prevalence, severity, and preventability of ADEs in patients presenting at EDs in 2 university-affiliated tertiary care hospitals in the Canadian province of Newfoundland and Labrador. METHODS: A retrospective chart review was conducted on a stratified random sample (n = 1458) of adults (>/=18 y) who presented to EDs from January 1 to December 31, 2005. Prior to the chart review, the sample frame was developed by first eliminating visits that were clearly not the result of an ADE. The ED summary of each patient was initially reviewed by 2 trained reviewers in order to identify probable ADEs. All eligible charts were subsequently reviewed by a clinical team, consisting of 2 pharmacists and 2 ED physicians, to identify ADEs and determine their severity and preventability. RESULTS: Of the 1458 patients presenting to the 2 EDs, 55 were determined to have an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.4%. Prevalence increased with age (0.7%, 18-44 y; 1.9%, 45-64 y; 7.8%, >/=65 y) and the mean age for patients with ADEs was higher than for those with no ADEs (69.9 vs 63.8 y; p < 0.01). A higher number of comorbidities and medications was associated with drug-related visits. Approximately 29% of the ADEs/PADEs identified were considered to be preventable, with 42% requiring hospitalization. Cardiovascular agents (37.4%) were the most common drug class associated with ADEs/PADEs. CONCLUSIONS: Adult ADE-related ED visits are frequent in Newfoundland and Labrador, and in many cases are preventable. Further efforts are needed to reduce the occurrence of preventable ADEs leading to ED visits.

PMID: 20233911 [PubMed - as supplied by publisher]

[Read more →]

Effects of Inhaled Corticosteroids in Monotherapy or Combined with Long-Acting {beta}2-Agonists on Mortality Among Patients with Chronic Obstructive Pulmonary Disease (April).

Ann Pharmacother. 2010 Mar 16;

Authors: Cyr MC, Beauchesne MF, Lemière C, Aaron SD, Blais L

BACKGROUND: The benefits of inhaled corticosteroids (ICS) in reducing the mortality related to chronic obstructive pulmonary disease (COPD) are controversial. OBJECTIVE: To estimate whether ICS in monotherapy or in combination with long-acting beta2-agonists (LABA) reduces the mortality rate among COPD patients compared to those treated with LABA monotherapy. METHODS: Using data from the Canadian province of Quebec’s health administrative databases, a nested case-control study was conducted. A cohort of COPD patients aged 50 years and over between 1996 and 2000 was initially formed. Patients were included if they filled at least 6 prescriptions of an inhaled bronchodilator, received at least 1 medical service for COPD, and did not receive any diagnosis of asthma over a 12-month period. For each case of death identified in the cohort, up to 37 controls were time matched. For cases and controls, the exposure to ICS and LABA was assessed within the 3 months prior to the date of death for cases and date of selection for controls. Adjusted mortality rate ratios were estimated by conditional logistic regression comparing patients using ICS monotherapy or ICS/LABA combination therapy with patients using LABA monotherapy. RESULTS: This study included 5996 cases of death and 54,750 controls. The mortality rates were found to be lower among users of ICS monotherapy than users of LABA monotherapy (OR 0.69; 95% CI 0.53 to 0.88) and lower among users of an ICS/LABA combination than users of LABA monotherapy (OR 0.73; 95% CI 0.56 to 0.96). No significant differences were observed between users of ICS/LABA combination therapy and users of ICS monotherapy (OR 1.07; 95% CI 0.93 to 1.23). CONCLUSIONS: ICS were found to be associated with a reduction in mortality rate when compared to LABA among patients with COPD. However, the ICS/LABA combination therapy did not provide any additional benefit on mortality when compared to ICS monotherapy.

PMID: 20233915 [PubMed - as supplied by publisher]

[Read more →]