NURS572_Drugs that Target the Bacterial Cell Wall II.pdf -...

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9/5/2019 Introduction 1/7 Drugs that Weaken the Bacterial Cell Wall II: Cephalosporins, Carbapenems, and Others Cephalosporins and Carbapenems Cephalosporins 1st generation 2nd generation 3rd generation 4th generation 5th generation Carbapenems Imipenem [Primaxin] Meropenem [Merrem IV] Ertapenem [Invanz] Cephalosporins Cephalosporin antibiotics are similar in structure and action to penicillins Bactericidal Active against a broad spectrum of pathogens Toxicity is low Because of these characteristics, the cephalosporins are popular therapeutic agents and constitute our most widely used group of antibiotics Hospitals in the U.S. spend more money on cephalosporins than all other antibiotics combined Chemistry All cephalosporins are derived from the same nucleus, which contains a beta-lactam ring Mechanism of Action Similar to action of penicillins Bind to penicillin-binding proteins Disrupting cell wall synthesis Activating autolysins (enzymes that cleave bonds in the cell wall) The resulting damage to the cell wall causes death by lysis Like penicillins, cephalosporins are most effective against cells undergoing active growth and division
9/5/2019 Introduction 2/7 Resistance Principal cause of cephalosporin resistance is production of beta-lactamases Beta-lactamases are enzymes that cleave the beta-lactam ring of cephalosporins, thereby rendering them inactive Not all cephalosporins are equally susceptible to beta-lactamases 1st generation: most are destroyed by beta-lactamases 2nd generation: less sensitive to destruction 3rd and 4th generation: highly resistant to destruction In some cases, bacterial resistance results from production of altered penecillin-binding proteins such that they have a low affinity for cephalosporins Methicillin-resistant staphylococci produce these unusual PBPs and are resistant to cephalosporins as a result Classification of Cephalosporins Grouped into five generations, based on the order of their introduction into clinical use Generations differ significantly with respect to antimicrobial spectrum and susceptibility to beta- lactamases In general, as you progress from 1st generation to 5th generation agents, there is: Increasing activity against gram-negative bacteria and anaerobes Increasing resistance to destruction by beta-lactamases Increasing ability to reach the cerebrospinal fluid Major Differences Between Cephalosporin Generations Class Activity Against Gram Negative Bacteria Resistance to Beta- lactamases Distibution to CSF Activity Against MRSA 1st Low Low Poor Low 2nd Higher Higher Poor Low 3rd Higher Higher Good Low 4th Highest Highest Good Low 5th Highest Highest Good High Cephalosporins: Pharmacokinetics Absorption Because of poor absorption from the GI tract, many cephalosporins must be administered parenterally (IM or IV) Of the 25 cephalosporins used in the U.S., only 12 can be administered by mouth
9/5/2019 Introduction

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