Antibiotic Resistance Mechanisms PDF

In The Name Of GOD Department of Microbiology School of medicine Tehran University of Medical Science Antimicrobial Agents (Part II) Fereshteh Jabalameli, PhD Associate Professor in Microbiology [email protected] 1 Resistanc...

In The Name Of GOD Department of Microbiology School of medicine Tehran University of Medical Science Antimicrobial Agents (Part II) Fereshteh Jabalameli, PhD Associate Professor in Microbiology [email protected] 1 Resistance of bacteria to antimicrobial agents ❖ Intrinsic (Natural) ❖ Acquired 1- Chromosomal Resistance Mutations 2- Extra chromosomal Resistance Plasmids 2 1- Alteration of the Drug's Target Site 2- Enzymatic Destruction or Inactivation of Drug 3-Decreased permeability 4- Rapid Efflux (Ejection) of the Antibiotic 5- Use of alternate metabolic pathway 3 1- Alteration of the Drug's Target Site  Binding site on target is altered so drug has no effect  Erythromycin-resistant organisms have an altered receptor on the 50S subunit of the ribosome 4 2- Enzymatic Destruction or Inactivation of Drug  Microbes inactivate drugs by producing enzymes that alter drug structure  Betalactamases ▪ Chloramphenicol acetyltransferase 5 3-Decreased permeability  The receptor that transports the drug is altered, the drug cannot enter the cell  Aminoglycoside resistance  Resistance to polymyxins 6 4- Rapid Efflux (Ejection) of the Antibiotic  Specialized membrane proteins are activated and pump the drug out of the cell Resistance to  Tetracyclines  Macrolides  Fluoroquinolones 7 5- Use of alternate metabolic pathway  The drug has blocked the usual metabolic pathway so the microbe using an alternate, unblocked pathway  Sulfonamide and trimethoprim Bypass of the pathway Inhibiting by drug 8 1) Decreased concentration of antibiotic at the cell wall target site Only in gram-negative bacteria ✓ Changes in proteins (porins) ✓ Alter size or charge of channels 9 2) Decreased binding of the antibiotic to the PBP, ✓ Overproduction of PBP (a rare occurrence) ✓ Acquisition of a new PBP (methicillin resistance in Staphylococcus aureus) ✓ Modification of PBP (penicillin resistance in Streptococcus pneumoniae) 10 3) Hydrolysis of the antibiotic by bacterial enzymes, β-lactamases ✓ Penicillinases ✓ Cephalosporinases ✓ Carbapenemases Extended-spectrum β-lactamases [ESBLs] Active against all penicillins and cephalosporins Are commonly encoded on plasmids 11 Microorganisms resistant to two drugs by a mechanism of action  Between agents are closely related chemically ✓ Different aminoglycosides ✓ Beta- lactams ✓ Colistin and Polymyxin B 12 1) Sufficiently high levels of the drug in the tissues 2) Administering two drugs that do not give cross-resistance 3) Avoiding exposure of microorganisms to a valuable drug by limiting its use, especially in hospitals 13  Kirby Bauer Method (Disk Diffusion) – Qualitative  Serial dilution Method- Quantitative Minimal Inhibitory Concentration (MIC)  E-Test - Quantitative 14  ‫س‬ ‫م‬‫نع‬ ‫ی‬ ‫ا‬ ‫ا‬ ‫گ‬ ‫ست‬ ‫تندر ی‪ ،‬و ر رت ن ت اه ت‬ ‫‪15‬‬