Other Beta - lactam Antibiotics
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1 Other Beta - lactam Antibiotics Assistant Professor Dr. Naza M. Ali Lec 5 8 Nov 2017
2 Lecture outlines Other beta lactam antibiotics Other inhibitors of cell wall synthesis
3 Other beta-lactam Antibiotics A. Carbapenems B. Monobactam C. Beta-Lactamase inhibitors
4 A. Carbapenems Chemically different from penicillins but retaining the beta-lactam ring structure. Imipenem, Meropenem, Ertapenem, Doripenem Have wide activity against gram positive cocci, gram negative rods, anaerobes.
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6 Plays a role in empiric therapy because it is active against penicillinase-producing gram-positive gram- negative organism anaerobes P. aeruginosa Imipenem resists hydrolysis by most β-lactamases, but not the metallo-β-lactamases. Used in combination with aminoglycoside for pseudomonal infection
7 Meropenem and doripenem have antibacterial activity similar to that of imipenem. Ertapenem lacks coverage against P. aeruginosa, Enterococcus species. They are used by IV & are useful for infections caused by organism resistant to other antibiotics.
8 They are drugs of choice for infections caused by Enterobacter. Imipenem is compounded with cilastatin to protect it from metabolism by renal dehydropeptidase. Imipenem & meropenem are administered IV and penetrate well into body tissues & fluids, including CSF when meninges are inflamed.
9 B. Monobactam Drugs with monocyclic beta-lactam ring. Aztreonam is resistant to action of beta - lactamases. has antimicrobial activity against gram-negative rods (Enterobacteriaceae) including pseudomonas It lacks activity against gram-positive organisms and anaerobes.
10 It is administered (IV or IM) Is excreted in urine, it can accumulate in patients with renal failure. Aztreonam is relatively nontoxic, can use as alternative for treating patients who are allergic to penicillins or cephalosporins.
11 C. Beta-Lactamase Inhibitors Hydrolysis of the beta-lactam ring by enzymatic cleavage or by acid, destroys the antimicrobial activity. Clavulanic acid, Sulbactum, Tazobactam contain a beta-lactam ring but, by themselves, do not have significant antibacterial activity. They bind to and inactivate beta-lactamases protecting the antibiotics that are substrates for these enzymes.
12 Clavulanic acid & Amoxicillin combination.
13 Carbapenem: Imipenem, Meropenem differ in str contain betalactam ring Gm+ cocci gm- rods (enterobacteriaceae) anaerobes pseudomonas +aminoglycosid IV Monobactam: Aztreonam Monocyclic beta lactam ring narrow spec. -ve rode No toxic,safe IM,IV P. aeruginosa No activity for +ve Beta-lactam inhibitors: Clavulanic acid, Sulbactam, tazobactam Contain beta lactum ring, do not have significant antibacterial activity Oral, parenteral
14 Other Inhibitors of Cell Wall Synthesis 1. Vancomycin 2. Teicoplanin same characteristics of Vancomycin 3. Telvancin 4. Daptomycin 5. Fosfomycin 6. Bacitracin 7. Polymyxins
15 Vancomycin It is Bactericidal, tricyclic glycopeptide Time dependent Mechanism of action: It inhibits synthesis of bacterial cell wall phospholipids by binding to D-Ala-D-Ala side chain
16 Antibacterial spectrum 1. Is effective against gram-positive organisms 2. It has been lifesaving in the treatment of MRSA, MRSE (methicillin-resistant Staphylococcus epidermidis) Enterococcal infections 3. Oral vancomycin is a backup antibiotic-associated colitis due to Clostirdium difficile
17 4. Is used in individuals with prosthetic heart valves and in patients undergoing implantation with prosthetic devices. 5. Vancomycin acts synergistically with aminoglycosides, the combination used in the treatment of enterococcal endocarditis.
18 Antimicrobial spectrum of vancomycin.
19 Pharmacokinetics Slow IV infusion (60-90 minutes) is employed for treatment of systemic infections or for prophylaxis. Half life is 6-10hr Dosage must be adjusted in renal failure, because the drug will accumulate.
20 Adverse effects Fever, chills, and/or phlebitis at the infusion site. Flushing (red man syndrome) and shock results from histamine release associated with a rapid infusion.
21 Dose-related hearing loss in patients with renal failure who accumulate the drug. Ototoxicity and nephrotoxicity are more common when vancomycin is administered with aminoglycoside.
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23 Daptomycin It is bactericidal concentration dependent antibiotic Spectrum of activity limited to gram positive organism including MRSA. For the treatment of complicated skin and skin structure infections and bacteremia caused by S. aureus. Daptomycin is inactivated by pulmonary surfactants so not indicated in the treatment of pneumonia.
24 Fosfomycin: Is rapidly absorbed after oral administration and distributes well to the kidneys, bladder, and prostate. The drug is excreted in its active form in the urine and feces. It maintains high concentrations in the urine over several days, allowing for a one-time dose for the treatment of urinary tract infections
25 Bacitracin: interfere with late stage in cell wall synthesis in gram-positive organism, used topically because of nephrotoxicity.
26 Telavancin Is an alternative to vancomycin Concentration dependent Bactericidal Act by inhibition bacterial cell wall synthesis and disruption of the bacterial cell membrane. Active against : MRSA, Streptocccus pyogenes Penicillin-resistant streptococcus pneumonia
27 Polymyxins Are cation polypeptides that bind to phospholipids on the bacterial cell membrane of gram-negative bacteria They have a detergent-like effect that disrupts cell membrane integrity, leading to leakage of cellular components and ultimately cell death. Polymyxins are concentration-dependent bactericidal agents
28 Active against most clinically important gram-negative bacteria, including: P. aeruginosa, E. coli, K. pneumoniae, Acinetobacter species, and Enterobacter species. polymyxin B and colistin ( polymyxin E ) Polymyxin B is available in parenteral, ophthalmic, and topical preparations.
29 Colistin is only available as a prodrug, colistimethate sodium, which is administered IV or inhaled via a nebulizer. The use of these drugs has been limited for a long time, due to the increased risk of nephrotoxicity and neurotoxicity (slurred speech, muscle weakness) when used systemically. with the increase in gram-negative resistance, they have seen a resurgence in use and are now commonly used as salvage therapy for patients with multidrug-resistant infections. Careful dosing and monitoring of adverse effects are important to maximize the safety and efficacy of these agents.
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