Targeting reperfusion injury in acute myocardial infarction: a review of reperfusion injury pharmacotherapy.

Expert Opin Pharmacother. 2012 Jun;13(8):1153-75

Authors: Sharma V, Bell RM, Yellon DM

Abstract
Introduction: Acute myocardial infarction (AMI) (secondary to lethal ischemia-reperfusion [IR]) contributes to much of the mortality and morbidity from ischemic heart disease. Currently, the treatment for AMI is early reperfusion; however, this itself contributes to the final myocardial infarct size, in the form of what has been termed 'lethal reperfusion injury'. Over the last few decades, the discovery of the phenomena of ischemic preconditioning and postconditioning, as well as remote preconditioning and remote postconditioning, along with significant advances in our understanding of the cardioprotective pathways underlying these phenomena, have provided the possibility of successful mechanical and pharmacological interventions against reperfusion injury. Areas covered: This review summarizes the evidence from clinical trials evaluating pharmacological agents as adjuncts to standard reperfusion therapy for ST-elevation AMI. Expert opinion: Reperfusion injury pharmacotherapy has moved from bench to bedside, with clinical evaluation and ongoing clinical trials providing us with valuable insights into the shortcomings of current research in establishing successful treatments for reducing reperfusion injury. There is a need to address some key issues that may be leading to lack of translation of cardioprotection seen in basic models to the clinical setting. These issues are discussed in the Expert opinion section.

PMID: 22594845 [PubMed - in process]

Ceftaroline fosamil for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection.

Expert Opin Pharmacother. 2012 Jun;13(8):1177-86

Authors: Casapao AM, Steed ME, Levine DP, Rybak MJ

Abstract
Introduction: Bacterial resistance is increasing on a global basis, making treatment options more limited. The development of new agents to meet this threat is a matter of urgency. Ceftaroline fosamil , a member of an advanced cephalosporin class of antimicrobials, is currently approved by the US Food and Drug Administration for use in for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia. Ceftaroline displays activity against Gram-positive and Gram-negative bacteria, including both methicillin-susceptible and resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae (including penicillin- and ceftriaxone-resistant strains), respiratory pathogens (such as Moraxella catarrhalis and Haemophilus influenzae, including beta-lactamase-producing strains) and limited coverage against Enterobacteriaceae. Areas covered: Chemistry, mechanism of action, spectrum of activity, resistance, pharmacokinetics/pharmacodynamics, indications for use, safety and special populations are covered in this review. Expert opinion: Ceftaroline's unique activity against MRSA and penicillin- and ceftriaxone-resistant S. pneumoniae strains is due to its high affinity for penicillin binding protein (PBP)-2a and PBP-2x, respectively. In randomized, double-blinded, clinical trials, ceftaroline fosamil was found to be non-inferior to ceftriaxone for the treatment CABP and to vancomycin plus aztreonam for ABSSSI. Substantial differences between the cephalosporins exist. Ceftaroline has unique characteristics that may make it useful in specific clinical circumstances, especially against multi-drug-resistant Gram-positive organisms.

PMID: 22594846 [PubMed - in process]