Cephalosporins PDF

Cell Wall Synthesis Inhibitors Cephalosporins  Fourth Generation Fifth Generation Cephalosporin: Cefepime Cephalosporin: Cetobiprole  Cephalosporins R groups determine spectrum of activity and pharmacological properties Mechanism of action/resist...

Cell Wall Synthesis Inhibitors Cephalosporins  Fourth Generation Fifth Generation Cephalosporin: Cefepime Cephalosporin: Cetobiprole  Cephalosporins R groups determine spectrum of activity and pharmacological properties Mechanism of action/resistance and class pharmacology essentially the same as penicillins  1st Generation Cephalosporins: Cefazolin, Cephalexin, Cephadroxil Excellent against susceptible staph and strep Modest activity against G- Cefazolin given parentally, others orally Excreted by kidneys unmetabolized Good for staph and strep skin and soft tissue infections  2nd Generation Cephalosporins Cefaclor, cefuroxime, cefprozil, cefotetan, cefoxitine, cefamandole Modest activity against G+, increased activity against G-, works against anaerobes Absorption and excretion same as first gen. Good for treating: – respiratory tract infections – intra-abdominal infections – pelvic inflammatory disease – diabetic foot ulcers  3rd Generation Cephalosporins Cefotaxime, ceftriaxone, cefpodoxime, cefixime, cedinir, cefoperazone Broad spectrum killers Drugs of choice for serious infections No effect against Listeria and beta-lactamase producing pneumococci Cefpodoxime and cefixime are given orally, others parentally Most excreted by kidney Therapeutic uses – Bacterial meningitis (2 exceptions cefoperazone, cefixime) – Life-threatening G- sepsis  Fourth Generation Cephalosporin: Cefepime – Same antimicrobial spectrum as third generation but resists more beta-lactamases – Given parentally, excellent penetration into CSF – Good for nosocomial infections  Toxicity/Contraindications of Cephalosporins Hypersensitivity reactions (uncommon) essentially same as for penicillins Cross-reaction between 2 classes Other adverse effects: – Pain at injection site – Phlebitis after IV injection – When given with aminoglycosides, may increase nephrotoxicity – Drugs containing methylthiotetrazole (eg cefamandole, cefaperazone, cefotetan)may cause hypoprothrombinemia and disulfiram-like reaction.  4. Carbapenems Imipenem, Meropenem, Ertapenem Effect on microbes and pharmacology of carbapenems similar to penicillins – Wider G+ activity, G-, and anaerobes For pseudomonal infections: given with aminoglycosides Parenteral administration Drugs of choice for infections caused by Enterobacter.  5. Monobactam: Aztreonam Works only on G-, including Pseudomonas aeruginosa Useful for treating G- infections that require a beta-lactam because it does not elicit hypersensitivity reactions  Toxicity/Contraindications of Carbapenems Nausea and vomiting (common) Hypersensitivity reactions (uncommon) – Essentially the same as for penicillins, exception is the monobactam – Cross-reactivity is possible, exception is the monobactam Cell Wall Synthesis Inhibitors (Non-B-lactams) 1. Vancomycin 2. Daptomycin 3. Teicoplanin 4. Telvancin 5. Bacitracin  1. Vancomycin Vancomycin is a tricyclic Bacitracin is a mixture of glycopeptide polypeptides that also inhibits bacterial cell wall Effective against multiple synthesis. drug-resistant organisms, It is active against a wide such as MRSA and variety of gram-positive enterococci. organisms. Concerns about the Its use is restricted to emergence of vancomycin topical application resistance. because of its potential for nephrotoxicity with systemic use. A. Mode of action of vancomycin It inhibits: This prevents the transglycosylation step in – synthesis of bacterial peptidoglycan cell wall polymerization, thus weakening the cell wall phospholipids and damaging the – peptidoglycan underlying cell membrane. polymerization by binding to the D-Ala- Inhibits cell wall synthesis D-Ala side chain of by inhibiting the precursor peptidoglycan synthetase pentapeptide. B: Antibacterial Spectrum Vancomycin is effective primarily against gram- positive organisms. It has been lifesaving in the treatment of: – MRSA – methicillin-resistant Staphylococcus epidermidis (MRSE) infections – enterococcal infections. C: The use of vancomycin should be restricted to: 1. the treatment of serious infections caused by b- lactam resistant, gram-positive microorganisms or 2. for patients with gram-positive infections who have a serious allergy to the b-lactams. Oral vancomycin: – is limited to treatment for potentially life-threatening, antibiotic-associated colitis due to C. difficile or staphylcocci.  Treatment of vancomycin-resistant organisms: – Daptomycin – quinopristin/dalfopristin – linezolid Vancomycin acts synergistically with the aminoglycosides, and this combination can be used in the treatment of enterococcal endocarditis. D. Pharmacokinetics of Vancomycin A. Absorbance 1. usually given IV over an hour 2. can be given orally for pseudomembranous colitis B. Fate after absorption 1. 30% of drug bound to serum proteins 2. appears in various bodily fluids, including CSF if inflammation is present C. Excretion - kidneys E. Toxicity/Contraindications A. Red-man syndrome (common) 1. erythematous or urticarial reaction to rapid infusion 2. mast cells are releasing histamine because of vancomycin’s toxicity B. Ototoxicity and nephrotoxicity (uncommon to rare) due to excessively high concentrations Red Man Syndrome (Erythrodermatitis) 2. Others: for treating infections caused by resistant gram-positive organisms, including: – MRSA – Vancomycin-resistant enterococci (VRE). 1. Daptomycin 2. Teicoplanin 3. Telvancin: A semi-synthetic lipoglycopeptide