Antibacterial Agents PDF

Dr. Özge YILMAZLI  Used in the treatment of infectious diseases  Prevents bacterial increasing or kill  Natural or synthetic agents The effects of antibiotics  Two types of antibiotics,  Bactericidal (killing)  Bacteriostatic (inhibits multiplying)  Narrow-spectrum drugs – acting on only...

Dr. Özge YILMAZLI  Used in the treatment of infectious diseases  Prevents bacterial increasing or kill  Natural or synthetic agents The effects of antibiotics  Two types of antibiotics,  Bactericidal (killing)  Bacteriostatic (inhibits multiplying)  Narrow-spectrum drugs – acting on only a few different pathogens  Broad spectrum drugs – acting on many different pathogens Antimicrobic features: • Selective toxicity • Broad spectrum effect • Bacteriosidal effect Pharmacological features: • Not toxic for host • Pass through into tissues and body fluids  Cell wall synthesis inhibition  Cytoplasmic membrane function inhibition  Protein synthesis inhibition  Nucleic acid inhibition  Beta-lactams The inhibitors of bacterial cell wall  Glycopeptides  Bacitracin  Cycloserine  Isoniazid  Ethionamide  Ethambutol The inhibitors of bacterial cell wall  The main content of the cell wall is the peptidoglycan chain  These chains are cross-linked with peptide bonds to form a strong structure  Making chains and cross-links: under the control of transpeptidase, carboxypeptidase and transglycosylase enzymes  These enzymes are members of serine proteases and referred to as penicillin binding proteins (PBPs) The inhibitors of bacterial cell wall  They have a 4-membered beta-lactam ring in their structure.  They inhibit the last step of peptidoglycan synthesis (transpeptidation reaction)  Clavulanic acid  Sulbactam  Tazobactam They act by inhibiting the β-lactamase enzyme. β-lactamase: an enzyme that inactivates the antibiotic by breaking β-lactam ring Combined use with beta-lactam antibiotics 𝜷 − 𝑳𝒂𝒄𝒕𝒂𝒎 𝑨𝒏𝒕𝒊𝒃𝒊𝒐𝒕𝒊𝒄𝒔 − Penicillins A) Natural penicillins Penicillin G: It is inactivated by stomach acide, IV use is possible for a limited number of susceptible bacteria Penicillin V: acide resistant so oral form can be used 𝜷 − 𝑳𝒂𝒄𝒕𝒂𝒎 𝑨𝒏𝒕𝒊𝒃𝒊𝒐𝒕𝒊𝒄𝒔 − Penicillins B) Penicillinase-Resistant Penicillins Methicillin Oxacillin MONCD Nafcillin Cloxacillin Dicloxacillin Similar to natural penicillins; It is highly effective against staphylococci Methicilin resistant is common in both hospital and community-acquired isolates (MRSA) 𝜷 − 𝑳𝒂𝒄𝒕𝒂𝒎 𝑨𝒏𝒕𝒊𝒃𝒊𝒐𝒕𝒊𝒄𝒔 − Penicillins C) Aminopenicillins: Broad spectrum penicillins, Ampicillin and Amoxicillin D) Other penicillins Carbenicillin, Ticarcillin and Piperacillin have a broader spectrum of action of Gr(-) including Klebsiella, Enterobacter and Pseudomonas species. 𝜷 − 𝑳𝒂𝒄𝒕𝒂𝒎 𝑨𝒏𝒕𝒊𝒃𝒊𝒐𝒕𝒊𝒄𝒔 Cephalosporins and Cehpamycins First isolated from Cephalosporium mold Cephamycins are similar to cephalosporins but more resistant to β-lactamase hydrolysis because they contain oxygen instead of sulfur 1st Generation Cephalosporins: Gr (+) activity Cephalexin, cephalothin, Cefazolin, Cefapirin, Cefradin 𝜷 − 𝑳𝒂𝒄𝒕𝒂𝒎 𝑨𝒏𝒕𝒊𝒃𝒊𝒐𝒕𝒊𝒄𝒔 Cephalosporins and Cefamycins  2nd Generation Cephalosporins:  Increased Gr(-) activity  Cefochlor, Cefuroxime  3rd Generation Cephalosporins:  More resistant to β-lactamases  Cefoxitin, Cefotetan  4th Generation Cephalosporins:  Pass through the outer membrane of the Gram (-) bacteria easier and faster  Cefotaxime, Ceftazidime, Ceftriaxone, Cefixime  5th Generation Cephalosporins:  Cefepime and Cefpirom  Increased Gr(-) activity 𝛃 − 𝐋𝐚𝐜𝐭𝐚𝐦 𝐀𝐧𝐭𝐢𝐛𝐢𝐨𝐭𝐢𝐜𝐬  Imipenem, Doripenem, Ertapenem, Meropenem  They frequently prescribed and have broad- spectrum  Monobactams are narrow spectrum drugs, only aerobic/Gr(-) activity.  Aztreonam primarily used for Gr (-) bacteria The inhibitors of bacterial cell wall  Vancomycin  Teicoplanin Ineffective against Gram (-)!!  It binds to D-Ala-D-Ala chain and  prevents bridging between peptidoglycan chains. Bactericidal effect  High molecular weight  Can't pass through porins, so  Ineffective to Gram (-)  Some species are naturally resistant! (Lactobacillus…)  Enterococcus gallinarum and E. casseliflavus contain D- ala-D-ser and are also resistant  E. faecium and E. faecalis have VanA and VanB resistance genes The inhibitors of bacterial cell Wall- Polypeptids  Bacitracin is applied locally in the treatment of skin infections caused by Gr(+) bacteria  Isoniazid, Ethionamide, Ethambutol and Cycloserine are cell wall-effective antibiotics used in the treatment of Mycobacteria sp. Cell wall synthesis inhibition Cytoplasmic membrane function inhibition Protein synthesis inhibition Nucleic acid inhibition •Protein •Phospholipid  Polymyxins (A, B, C, D, E)  Obtained from Bacillus polymyxa  It acts as a detergent - binds to the outer membrane, increases cell permeability and causes cell to death!!!  Polymyxin B and E (colistin) have severe nephrotoxicity effect, so  It is used systemically in isolates sensitive to only colistin such as Acinetobacter and Pseudomonas  For Gr(+) ineffective - Why? Inhibition of cytoplasmic membrane function Daptomycin Effective against gram positive bacteria can not pass through the Gr(-) cell wall and reach the cytoplasmic membrane. It binds irreversibly at the cytoplasmic membrane, causing disruption in depolarization and ion exchange, cell death Staphylococci, Streptococci and Vancomycin Resistant Enterococci (VRE)  Cell wall synthesis inhibition  Inhibition of cytoplasmic membrane function  Protein synthesis inhibition  Nucleic acid inhibition  70S ribosome  30S  50S • Aminoglycosides (bactericidal) • Tetracyclines (bacteriostatic) • Glycylcyclines (bacteriostatic) Aminoglycosides  Bactericidal effect  Streptomycin, Neomycin, Kanamycin, Tobramycin, Gentamicin and Sisomycin  All binds irreversibly to the 30S ribosomal subunit.  cause misreading of mRNA / early separation of mRNA from ribosome  Many Gr(-) bacilli and some Gr(+) bacteria Aluminum, calcium, magnesium and iron in the foods: chelating with tetracycline and cause to it’s inactivation Accumulation in teeth and bones!!! First choice for: Brucellosis, Lyme disease, Mycoplasma pneumonia, Tularemia, Rickettsiosis Tetracyclines  Bacteriostatic  Reversible attachment to 30S, inhibits of aminoacyl-tRNA binding to 30S ribosome-mRNA complex  Because the drug binds onto tRNA’s place!!!  Tetracycline  Doxycycline  Minocycline  Macrolides  Ketolides  Lincosamides  Oxazolidinones  Chloramphenicol  Streptogramins MKLOCS The first model is Erythromycin It’s modifications: Azithromycin, Clarithromycin and Roxithromycin It binds reversibly to 50 S ribosomal subunit and blocks polypeptide elongation. 1. Quinolones Nalidixic acid Ciprofloxacin Levofloxacin Moxifloxacin 2. Rifampin and Rifabutin 3. Metronidazole 4. Antimetabolites Sulfonamides Trimethoprim Dapsone  The most widely used class of antibiotics  It inhibits DNA topoisomerase type II (DNA gyrase) or type IV enzymes that necessary for DNA replication, recombination and DNA repair.  Nalidixic acid was the first quinolone used in the clinic.  Urinary tract infection  Replaced by cipro, levo and moxifloxacin (fluoroquinolones)  Binds to DNA-dependent RNA polymerase,  prevents the initiation of RNA synthesis  Extremely effective against aerobic Gr(+) cocci  Gr(-) bacteria are naturally resistant It is used orally in the treatment of Trichomonas vaginitis Also effective against amebiasis, giardiasis and anaerobic bacterial infections İneffective against aerobic / facultative anaerobics It works by breaking down bacterial DNA Sulfonamids: Competes with p-aminobenzoic acid and inhibits the first step of folic acid synthesis  It inhibits the dihydropteroate synthetase enzyme so the synthesis of dihydropteroic acid from PABA. Antimetabolites Trimethoprim  By inhibiting the dihydrofolate reductase enzyme, it prevents the formation of tetrahydrofolic acid from dihydrofolic acid.  Often used as TMP/SXT  THANKS FOR YOUR ATTENTİON