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Drugs That Weaken the Bacterial Cell Wall II: Cephalosporins, Carbapenems, Vancomycin, Telavancin, Aztreonam, Teicoplanin, and Fosfomycin Cephalosporins Most widely used group of antibiotics Beta-lactam antibiotics Similar to penicillin structure Bactericidal Usually given parenterally Toxicity is low Cephalosporins Mechanism of action Bind to penicillin-binding proteins (PBPs), disrupt cell wall synthesis, and cause cell lysis Most effective against cells undergoing active growth and division Resistance Beta-lactamases (cephalosporinases) • Third- and fourth-generation agents more resistant than first- and second-generation agents Classification of Cephalosporins First-generation Second-generation Cefaclor (Ceclor) Third-generation Cefazolin (Ancef) Cefoperazone (Cefobid) Fourth-generation Cefepime (Maxipime) Cephalosporins Drug interactions Probenecid Alcohol Drugs that promote bleeding Calcium and ceftriaxone Adverse effects Allergy Bleeding Thrombophlebitis Cephalosporins Therapeutic uses 19 cephalosporins currently used in United States First- and second-generation agents rarely used for active infection Third-generation • Preferred therapy for several infections • Highly active against gram-negative organisms • Able to penetrate to cerebrospinal fluid (CSF) Fourth-generation • Broad spectrum • Penetration to CSF is good Carbapenems Beta-lactam antibiotics have an extremely broad antimicrobial spectrum with low toxicity Not active against methicillin-resistant Staphylococcus aureus (MRSA) Imipenem (Primaxin) Meropenem (Merrem IV) Ertapenem (Invanz) Doripenem (Doribax) Vancomycin (Vancocin, Vancoled) Action Inhibits cell wall synthesis Uses Severe infections only Methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis Oral dose used for Clostridium difficile if metronidazole was tried and found ineffective Vancomycin (Vancocin, Vancoled) Adverse effects Ototoxicity (reversible or permanent) Red man syndrome Thrombophlebitis (common) Thrombocytopenia (rare) Allergy Monobactam Aztreonam (Azactam) Binds to penicillin-binding protein 3 (PBP3) Narrow antimicrobial spectrum Gram-negative aerobic bacteria only Must be given parenterally Adverse effects similar to those of other betalactam antibiotics Teicoplanin (Targocid) Similar in structure and actions to vancomycin Does not have beta-lactam ring MRSA and C. difficile are sensitive to drug Not approved in United States (approved in Japan and Europe) No infusion-related reactions Fosfomycin (Monurol) Approved for single-dose therapy of uncomplicated urinary tract infection (UTI) caused by Escherichia coli or Enterococcus faecalis Disrupts the synthesis of peptidoglycan polymer strands that compose the cell wall Side effects Most common: diarrhea, headache, vaginitis, nausea