Estimating creatinine clearance: a meta-analysis.
Pharmacotherapy. 2011 Jul;31(7)…

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Impact of an antimicrobial allergy label in the medical record on clinical outcomes in ho…

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Safety of daptomycin in patients receiving hemodialysis.
Pharmacotherapy. 2011 Ju…

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Assessment of the 4Ts pretest clinical scoring system as a predictor of heparin-induced thrombocytopenia.
Pharmacotherapy. 2011 Feb;31(2):138-45
Authors: Strutt JK, Mackey JE, Johnson SM, Sylvia LM
To evaluate the util…

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Empiric antifungal therapy in patients with febrile neutropenia.
Pharmacotherapy. 2011 Apr;31(4):369-85
Authors: Ferrara JJ, Macdougall C, Gallagher JC
Abstract Invasive fungal infections, most commonly candidiasis or …

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Brand Name versus Generic Warfarin: A Systematic Review of the Literature.
Pharmacotherapy. 2011 Apr;31(4):386-93
Authors: Dentali F, Donadini MP, Clark N, Crowther MA, Garcia D, Hylek E, Witt DM, Ageno W,
Abstract T…

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Treatment of heart failure with preserved ejection fraction.

Pharmacotherapy. 2011 Mar;31(3):312-31

Authors: Barnes MM, Dorsch MP, Hummel SL, Koelling TM, Bleske BE

Abstract Heart failure contributes to more than 1 million hospitalizations annually and is one of the most common causes of repeat hospitalizations in the elderly. Previously, it was thought that mortality from heart failure with preserved ejection fraction (PEF) was lower than that from heart failure with reduced ejection fraction (REF), but more recent data infer similar mortality. Although the mortality rate in patients with heart failure with REF is decreasing, the mortality rate in patients with heart failure with PEF remains unchanged-possibly due to the lack of evidence-based treatment regimens or greater recognition of the disease. Without sufficient trials in patients with heart failure with PEF, clinicians are forced to extrapolate treatment from data proven to benefit patients with heart failure with REF. There is no question that clinical trials including only patients with heart failure with PEF are limited. In addition, the definition and clinical diagnosis of this syndrome are not clearly defined, and the guidelines available for treatment lack specificity in recommendations. To describe the current literature for the treatment of heart failure with PEF, we conducted a MEDLINE search of the English-language literature (1950-2009) to identify studies that pertain to the treatment of patients with heart failure with PEF. Ongoing clinical trials continue, but until data become available, clinicians must base their treatment strategies for heart failure with PEF on sparse information.

PMID: 21361741 [PubMed - in process]

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The DRESS Syndrome: The Great Clinical Mimicker.

Pharmacotherapy. 2011 Mar;31(3):332

Authors: Fleming P, Marik PE

Abstract The life-threatening DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is characterized by the presence of at least three of the following findings: fever, exanthema, eosinophilia, atypical circulating lymphocytes, lymphadenopathy, and hepatitis. This syndrome is difficult to diagnose, as many of its clinical features mimic those found with other serious systemic disorders. This idiosyncratic reaction occurs most commonly after exposure to drugs such as allopurinol, sulfonamides, and aromatic anticonvulsants such as phenytoin, phenobarbital, and carbamazepine. We describe a 44-year-old woman who was brought to the emergency department with new-onset hemorrhagic stroke. She was admitted to the intensive care unit where she received supportive care that included clonidine and hydralazine for blood pressure control and phenytoin for seizure prophylaxis. On hospital day 21, the patient developed signs and symptoms of severe sepsis. Despite receipt of broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam) and supportive care, the patient’s clinical condition worsened with progressive jaundice, severe oliguria, and labile blood pressures. All cultures revealed no growth, and her chest radiograph remained clear. Several days after the onset of her fever, the patient developed several hematologic abnormalities including thrombocytopenia, with schistocytes present on a peripheral smear. She also had an elevated lactate dehydrogenase level. A provisional diagnosis of thrombotic thrombocytopenic purpura was made; however, the patient then developed severe facial edema, nearly global erythroderma, and severe exfoliative dermatitis. A punch biopsy of the skin was compatible with the DRESS syndrome. Phenytoin, vancomycin, and piperacillin-tazobactam were discontinued, and the patient was started on systemic corticosteroids, with rapid resolution of her fever and eosinophilia and progressive improvement in her skin rash and multiorgan system dysfunction. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of DRESS syndrome and treatment with phenytoin. Clinicians should have a high index of suspicion for the DRESS syndrome in patients being treated with aromatic anticonvulsants who develop a sepsis-like syndrome. Furthermore, considering the potential severe effects associated with phenytoin, the risks and benefits should be carefully evaluated before using this agent for seizure prophylaxis.

PMID: 21361742 [PubMed - in process]

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Acute-on-chronic liver failure: the brain.

Curr Opin Crit Care. 2011 Feb 22;

Authors: García-Martínez R, Córdoba J

PURPOSE OF REVIEW: Brain disturbances, which are considered a form of hepatic encephalopathy, are common in acute-on-chronic liver failure. RECENT FINDINGS: Patients with hepatic encephalopathy exhibit sings of energy impairment that may participate in the development of disturbances in neurotransmission. Ammonia participates in the genesis of brain edema and in the development of oxidative stress injury to astrocytes. Neuroinflammation is a new element that has been described in experimental models. These mechanisms are involved in the genesis of cognitive sequels that may persist after liver transplantation. Clinical trials have demonstrated the value of drugs that decrease the production of ammonia in the intestines to prevent encephalopathy. In addition, improvement of circulatory dysfunction with the use of albumin and vasoconstrictors may prevent hepatic encephalopathy in acute-on-chronic liver failure. New drugs that act by enhancing ammonia disposal through the synthesis of nitrogenous metabolites have shown promising results. SUMMARY: A better knowledge of the pathogenesis of brain disturbances in acute-on-chronic liver failure provides the rationale for using ammonia-focused therapy in the prevention and treatment of encephalopathy. New therapies addressed to correct brain edema, circulatory dysfunction and inflammation may also be useful for encephalopathy and may improve the neurological outcome.

PMID: 21346567 [PubMed - as supplied by publisher]

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Acute-on-chronic liver failure: the liver and portal haemodynamics.

Curr Opin Crit Care. 2011 Feb 22;

Authors: Mookerjee RP

PURPOSE OF REVIEW: During acute-on-chronic liver failure (ACLF), the marked systemic inflammatory response and rapid deterioration in liver function are associated with a significant deterioration in organ perfusion and an appreciable rise in portal pressure. Indeed, the development of sepsis and multiorgan dysfunction that commonly follows presentation in these patients is intricately related to the severity of portal hypertension. It follows that understanding the drivers for rising portal pressure in ACLF will inform new therapies. RECENT FINDINGS: As this review aims to highlight, there has been a paradigm shift in understanding of the drivers of portal hypertension, from a prior focus on splanchnic vasodilatation and therapies targeting portal inflow, toward appreciation of increasing intrahepatic resistance as the trigger for further vascular derangement, especially in the context of systemic inflammatory responses. SUMMARY: By elaborating on those mechanisms that are especially perturbed by inflammatory responses, this article aims to show how this understanding has helped inform the identification of potential new targets for therapy in ACLF. Particular emphasis is given to agents with data supporting their progression toward clinical trials and those currently undergoing validation in clinical studies.

PMID: 21346568 [PubMed - as supplied by publisher]

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Drotrecogin alpha: a rational approach to the treatment of submassive pulmonary embolism?

Crit Care. 2011 Feb 22;15(1):123

Authors: Samama CM, Godier A

ABSTRACT: Combining therapeutic doses of low-molecular-weight heparins and increasing doses of recombinant activated protein C – Drotrecogin alpha (activated), or DAA – is of theoretical interest with regard to the control of coagulation activation. The study by Dempfle and colleagues presents new data showing that endogenous activated protein C levels do not increase in nonseptic patients with pulmonary embolism. However, the results of the addition of these two treatments are puzzling, leaving unresolved the questionable clinical relevance of this combination and the possible increase in bleeding risk.

PMID: 21345242 [PubMed - as supplied by publisher]

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Too early initiation of renal replacement therapy may be harmful.

Crit Care. 2011 Jan 26;15(1):112

Authors: Vinsonneau C, Monchi M

ABSTRACT: In an observational multicenter study, Elseviers and colleagues report that renal replacement therapy (RRT) in acutely ill patients treated for acute kidney injury is an independent risk factor for death. This result may question the benefit of the current practice of early RRT initiation.

PMID: 21345253 [PubMed - as supplied by publisher]

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Hospital resource utilization and costs of inappropriate treatment of candidemia.

Pharmacotherapy. 2010 Apr;30(4):361-8

Authors: Arnold HM, Micek ST, Shorr AF, Zilberberg MD, Labelle AJ, Kothari S, Kollef MH

STUDY OBJECTIVES: To evaluate the impact of inappropriate therapy–defined as delayed antifungal therapy beyond 24 hours from culture collection, inadequate antifungal dosage, or administration of an antifungal to which an isolate was considered resistant–on postculture hospital length of stay and costs, and to evaluate the relationship between modifiable risk factors, including failure to remove a central venous catheter, antifungal delay, and inadequate dosage, for an additive effect on hospital length of stay and costs. DESIGN: Single-center retrospective cohort study. SETTING: 1250-bed academic medical center. PATIENTS: One hundred sixty-seven consecutive adult patients admitted between January 2004 and May 2006 with culture-confirmed Candida bloodstream infections that occurred within 14 days of hospital admission and who received at least one dose of antifungal treatment. MEASUREMENTS AND MAIN RESULTS: Patients were stratified according to appropriateness of antifungal therapy. Appropriate therapy was defined as initiation of an antifungal to which the isolated pathogen was sensitive in vitro within 24 hours of positive culture collection, in addition to receipt of an adequate dose as recommended by the Infectious Diseases Society of America and the antifungal package insert. Postculture length of stay was the primary outcome and hospital costs the secondary outcome. An evaluation of modifiable risk factors was performed separately. Data were analyzed for 167 patients (22 in the appropriate therapy group and 145 in the inappropriate therapy group). Postculture length of stay was shorter in the appropriate therapy group (mean 7 vs 10.4 days, p=0.037). This correlated with total hospital costs that were lower in the appropriate therapy group (mean $15,832 vs $33,021, p<0.001.) A graded increase in costs was noted with increasing number of modifiable risk factors (p=0.001). CONCLUSION: Inappropriate therapy for Candida bloodstream infection occurring within 14 days of hospitalization was associated with prolonged postculture length of stay and increased costs. A rise in costs, but not length of stay, was noted with increasing modifiable risk factors.

PMID: 20334456 [PubMed - indexed for MEDLINE]

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Cethromycin: a promising new ketolide antibiotic for respiratory infections.

Pharmacotherapy. 2010 Mar;30(3):290-303

Authors: Rafie S, MacDougall C, James CL

Community-acquired pneumonia remains the primary infectious cause of death in the United States. At current levels of antimicrobial resistance, conventional agents are at risk of becoming less effective, and the need for new agents is pressing. Cethromycin is a new ketolide antibiotic being investigated for use in respiratory tract infections. To review its pharmacology, in vitro susceptibilities, pharmacokinetics, efficacy, safety, and drug interactions, we conducted a MEDLINE search restricted to English-language articles citing cethromycin or ABT-773 (its original designation) from 1990-May 2009. Additional data sources were identified from the references of selected articles. All published trials and available poster data citing cethromycin were selected for review. In vitro, cethromycin displays more potent antibacterial effects than its predecessor telithromycin. Cethromycin exhibits potent inhibition of both gram-positive and gram-negative respiratory pathogens. A new drug application for cethromycin was submitted to the United States Food and Drug Administration in 2008 for the treatment of community-acquired pneumonia. Clinical trial data in the treatment of respiratory tract infections support cethromycin’s efficacy. The limited safety data have not included any reports of hepatotoxicity. If cethromycin proves to be safe with regard to hepatotoxicity, it has great promise as an alternative to current standard therapy for community-acquired respiratory infections, especially pneumonia. Given current resistance levels, cethromycin could provide more reliable coverage against common respiratory pathogens than traditional agents in the beta-lactam and macrolide classes.

PMID: 20180612 [PubMed - indexed for MEDLINE]

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Ceftobiprole: first cephalosporin with activity against methicillin-resistant Staphylococcus aureus.

Pharmacotherapy. 2009 May;29(5):511-25

Authors: Vidaillac C, Rybak MJ

Ceftobiprole medocaril is the first member of a new series of advanced cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). The drug received an approvable letter from the United States Food and Drug Administration (FDA) in March 2008 and from Health Canada in June 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis. It has an established stability against hydrolysis by many gram-positive beta-lactamases and a higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older beta-lactams. Ceftobiprole activity does not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii. Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Ceftobiprole is available only for intravenous administration; recommended dosage regimens have not been approved by the FDA as of this writing. However, based on the Canadian package insert, expected dosage recommendations are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram-positive pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram-negative or both gram-positive and susceptible gram-negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2-hour infusion every 12 hours. Several precautions regarding hypersensitivity and drug incompatibility are reported. Ceftobiprole represents a promising option for the treatment of mono- and polymicrobial infections caused by multidrug-resistant gram-positive and susceptible gram-negative pathogens, but further toxicity and safety studies are warranted.

PMID: 19397461 [PubMed - in process]

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