2012 July 12

Ceftaroline Fosamil in the Treatment of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and Skin Structure Infections.

Jul 122012

Ceftaroline Fosamil in the Treatment of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and Skin Structure Infections.

Drugs. 2012 Jul 11;

Authors: Lodise TP, Low DE

Abstract

Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of ?-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum ?-lactamases, class B metallo-?-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation of lesion spread and absence of fever, was 74.0% in the ceftaroline fosamil group compared with 66.2% in the vancomycin plus aztreonam group (treatment difference 7.8%, 95% CI 1.3, 14.0). Clinical efficacy of ceftaroline fosamil in 1240 hospitalized adults with CAP was compared with that of ceftriaxone in two additional phase III trials (FOCUS 1 and FOCUS 2). Of note, because ceftriaxone does not have activity against MRSA, patients with confirmed or suspected MRSA CAP were excluded from the FOCUS trials. Results demonstrated that ceftaroline was noninferior to ceftriaxone, with 84.3% in the ceftaroline fosamil group achieving clinical cure compared with 77.7% in the ceftriaxone group (difference 6.7%, 95% CI 1.6, 11.8). An additional analysis of the trials was conducted in patients with moderate to severe CAP and at least one proven typical bacterial pathogen at baseline (i.e. CABP). Day 4 clinical response rates were 69.5% for ceftaroline and 59.4% for ceftriaxone (difference 10.1%, 95% CI -0.6, 20.6). In the phase III trials, adverse event rates were similar between groups. Overall, ceftaroline is well tolerated, which is consistent with the good safety and tolerability profile of the cephalosporin class. In summary, ceftaroline fosamil is a broad-spectrum parenteral cephalosporin with excellent in vitro activity against resistant Gram-positive pathogens, including MRSA, as well as many common Gram-negative organisms. It is a welcome treatment option for ABSSSI and CABP.

PMID: 22779432 [PubMed - as supplied by publisher]

Link to Article at PubMed

A comparison of the accuracy of clinical decisions based on full-text articles and on journal abstracts alone: a study among residents in a tertiary care hospital.

evid based med Start a Discussion »

Jul 122012

A comparison of the accuracy of clinical decisions based on full-text articles and on journal abstracts alone: a study among residents in a tertiary care hospital.

Evid Based Med. 2012 Jul 10;

Authors: Marcelo A, Gavino A, Isip-Tan IT, Apostol-Nicodemus L, Mesa-Gaerlan FJ, Firaza PN, Faustorilla JF, Callaghan FM, Fontelo P

Abstract

BackgroundMany clinicians depend solely on journal abstracts to guide clinical decisions.ObjectivesThis study aims to determine if there are differences in the accuracy of responses to simulated cases between resident physicians provided with an abstract only and those with full-text articles. It also attempts to describe their information-seeking behaviour.MethodsSeventy-seven resident physicians from four specialty departments of a tertiary care hospital completed a paper-based questionnaire with clinical simulation cases, then randomly assigned to two intervention groups-access to abstracts-only and access to both abstracts and full-text. While having access to medical literature, they completed an online version of the same questionnaire.FindingsThe average improvement across departments was not significantly different between the abstracts-only group and the full-text group (p=0.44), but when accounting for an interaction between intervention and department, the effect was significant (p=0.049) with improvement greater with full-text in the surgery department. Overall, the accuracy of responses was greater after the provision of either abstracts-only or full-text (p<0.0001). Although some residents indicated that 'accumulated knowledge' was sufficient to respond to the patient management questions, in most instances (83% of cases) they still sought medical literature.ConclusionsOur findings support studies that doctors will use evidence when convenient and current evidence improved clinical decisions. The accuracy of decisions improved after the provision of evidence. Clinical decisions guided by full-text articles were more accurate than those guided by abstracts alone, but the results seem to be driven by a significant difference in one department.

PMID: 22782923 [PubMed - as supplied by publisher]

Link to Article at PubMed

Efficacy and safety profile of dronedarone in clinical practice. Results of the Magdeburg Dronedarone Registry (MADRE study).

Int J Cardiol Start a Discussion »

Jul 122012

Efficacy and safety profile of dronedarone in clinical practice. Results of the Magdeburg Dronedarone Registry (MADRE study).

Int J Cardiol. 2012 Jul 9;

Authors: Said SM, Esperer HD, Kluba K, Genz C, Wiedemann AK, Boenigk H, Herold J, Schmeisser A, Braun-Dullaeus RC

Abstract

BACKGROUND: Dronedarone is a new antiarrhythmic agent that has only recently been approved for the therapy of atrial fibrillation (AF). Results regarding a broader spectrum of patients and experience accumulated in clinical practice are still very scarce. Therefore, we prospectively investigated the efficacy and tolerance of dronedarone in a real life setting. METHODS AND RESULTS: The study included 191 patients (85 women) aged 63±9.9years with a history of paroxysmal or persistent AF. Follow-up time was 14.3±4.9months. In patients with persistent AF, sinus rhythm was restored using electrical cardioversion prior to dronedarone administration. Each patient underwent standard ECG on a daily basis during the first 4days of treatment, and on days 7, 30 and 90, resp. After that, the patients had a follow-up visit every three months. Creatinine, creatine kinase, and hepatic enzymes were closely monitored. Clinical history was meticulously taken at multiple follow-up visits. Dronedarone maintained sinus rhythm in 33.5% (95% CI: 27%-40%), and AF recurrence rate was high: 66.5% (95% CI: 60%-73%). Adverse effects occurred in 31.9% (95% CI: 27%-38%) of the patients and necessitated permanent discontinuation of dronedarone in 22% (95% CI: 17%-27%). CONCLUSIONS: The results suggest that dronedarone may not be superior to available antiarrhythmic agents and caution against its use as a first line therapy in AF.

PMID: 22781508 [PubMed - as supplied by publisher]

Link to Article at PubMed

Effectiveness and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections in "Real Life": An International, Multicenter Poststudy Survey (ProREAL).

Arch Intern Med Start a Discussion »

Jul 122012

Effectiveness and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections in "Real Life": An International, Multicenter Poststudy Survey (ProREAL).

Arch Intern Med. 2012 May 14;172(9):715-22

Authors: Albrich WC, Dusemund F, Bucher B, Meyer S, Thomann R, Kühn F, Bassetti S, Sprenger M, Bachli E, Sigrist T, Schwietert M, Amin D, Hausfater P, Carre E, Gaillat J, Schuetz P, Regez K, Bossart R, Schild U, Mueller B, Proreal Study Team FT

Abstract

BACKGROUND In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. METHODS We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. RESULTS Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). CONCLUSIONS This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN40854211.

PMID: 22782201 [PubMed - in process]

Link to Article at PubMed

Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs.

BMJ Start a Discussion »

Jul 122012

Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs.

BMJ. 2012;345:e4388

Authors: Douglas IJ, Evans SJ, Hingorani AD, Grosso AM, Timmis A, Hemingway H, Smeeth L

Abstract

OBJECTIVE: To measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin.

DESIGN: Observational cohort study and self controlled case series.

SETTING: United Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration)

POPULATION: 24?471 patients receiving clopidogrel and aspirin.

MAIN OUTCOME MEASURES: The primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use.

RESULTS: Of the 24?471 patients prescribed clopidogrel and aspirin, 12?439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors.

CONCLUSION: The lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant.

PMID: 22782731 [PubMed - in process]

Link to Article at PubMed

Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases.

j pharm pharmacol Start a Discussion »

Jul 122012

Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases.

J Pharm Pharmacol. 2012 Apr;64(4):470-81

Authors: Rashikh A, Ahmad SJ, Pillai KK, Najmi AK

Abstract

OBJECTIVES: High blood pressure (BP) is a major risk factor for cardiovascular and renal complications. A majority of treated hypertensive patients still complain of high BP. The renin-angiotensin aldosterone system (RAAS) has been a centre-stage target for all the cardiovascular and cardio-renal complications. Aliskiren, is the first direct renin inhibitor (DRI) to be approved by the US FDA. Renin controls the rate-limiting step in the RAAS cascade and hence is the most favorable target for RAAS suppression.

KEY FINDINGS: This review article strives to summarize the pharmacokinetic, preclinical and clinical studies done so far pertaining to the efficacy of aliskiren. Further, the pharmacology of aliskiren has been comprehensively dealt with to enhance understanding so as to further research in this unfathomed area in the multitude of cardiovascular disorders and renal diseases.

SUMMARY: Aliskiren has been shown to have comparable BP-lowering effects to other RAAS inhibitors. Recent clinical trials have indicated that it might contribute significantly in combination with other agents for the protection of end-organ diseases.

PMID: 22420653 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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