Other β-lactam. A. Carbapenems:
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1 A. Carbapenems: Other β-lactam Carbapenems are synthetic β-lactam antibiotics Differ in structure from the penicillins in that the sulfur atom of the thiazolidine ring. Imipenem, meropenem, doripenem, and ertapenem are the drugs of this group currently available. Imipenem is compounded with cilastatin to protect it from metabolism by renal dehydropeptidase.
2 Antibacterial Spectrum: Imipenem resists hydrolysis by most β- lactamases. This drug plays a role in empiric therapy because it is active against β-lactamase producing gram-positive and gramnegative organisms, anaerobes, and P. aeruginosa.
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4 Pharmacokinetics: Imipenem/cilastatin and meropenem are administered IV Excreted by glomerular filtration. Imipenem undergoes cleavage by a dehydropeptidase found in the brush border of the proximal renal tubule. Inactive metabolite is resulted that is potentially nephrotoxic. Compounding the imipenem with cilastatin protects the parent drug and, thus, prevents the formation of the toxic metabolite. The other carbapenems do not require coadministration of cilastatin.
5 Monobactams β-lactam ring is not fused to another ring Aztreonam which is the only commercially available monobactam has antimicrobial activity Directed primarily against gram-negative pathogens. It lacks activity against gram positive organisms and anaerobes. Aztreonam is resistant to the action of most β-lactamases. Administered either IV or IM. Aztreonam is relatively nontoxic. it shows little cross-reactivity with antibodies induced by other β-lactams. May offer a safe alternative for treating patients who are allergic to other penicillins cephalosporins, or carbapenems.
6 Monobactams
7 β-lactamase Inhibitors Hydrolysis of the β-lactam ring.destroys the antimicrobial activity of a β-lactam antibiotic. β-lactamase inhibitors: Clavulanic Acid Sulbactam Tazobactam o Contain a β-lactam ring but, by themselves, do not have significant antibacterial activity or cause any significant adverse effects. o Bind to and inactivate β-lactamases, thereby protecting the antibiotics that are normally substrates for these enzymes. o The β-lactamase inhibitors are therefore formulated in combination with β-lactamase sensitive.
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10 Vancomycin Vancomycin has become increasingly important in the treatment of lifethreatening infections. MRSA infections. Methicillin-resistant Staphylococcus epidermidis (MRSE) infections Enterococcal infections.
11 Daptomycin Telavancin Fosfomycin Polymyxins
12 Protein Synthesis Inhibitors
13 Protein Synthesis Inhibitors o Antibiotics exert their antimicrobial effects by targeting bacterial ribosomes and inhibiting bacterial protein synthesis. o Bacterial ribosomes composed of 30S and 50S subunits. o Mammalian ribosomes have 40S and 60S subunits. o Selectivity minimizes potential adverse o Structure of mitochondrial ribosomes more closely resembles bacterial ribosomes. High concentration side effect(tetracyclines and chloramphenicol).
14 Mechanism of action: Tetracyclines
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16 Absorption Administration with dairy products or other substances that contain divalent and trivalent cations (magnesium, aluminum antacids or iron supplements) decreases absorption particularly for tetracycline.
17 Tetracyclines Bacteriostatic including gram-positive and gram-negative bacteria. Resistance to tetracyclines is: Efflux pump that expels drug out of the cell Enzymatic inactivation of the drug. Production of bacterial proteins that prevent tetracyclines from binding to the ribosome.
18 Contraindications: The tetracyclines should not be used in pregnant. Breast-feeding women. Children less than 8 years of age.
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life-threatening infections
Vancomycin Vancomycin has become increasingly important in the treatment of life-threatening infections. MRSA infections. Methicillin-resistant Staphylococcus epidermidis (MRSE) infections Enterococcal
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