5. Bacterial resistance .pdf

Antibiotics use for the treatment of bacterial infection...

Antibiotics use for the treatment of bacterial infection Efog Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity in (i.e.: they have the ability to kill or inhibit the growth of an invading microorganism without harming the cells of the host). Bacterial resistance Done By Fatma Altubaikh In most instances, the selective toxicity is relative, rather than absolute: or Dr Omamah Alfarisi Require the concentration of the drug be carefully 2nd yr Pharm D March 2024 user controlled to attack the microorganism while still being tolerated by the host. Bacterial resistance to antibiotics: Antibiotic resistance Resistance can be: Intrinsic Resistance: 11,0 Bacteria are described to be resistance to an antimicrobial drug if the Bacteria might survive an antibiotic due to intrinsic resistance through evolution maximal level of the agent that can be achieved or tolerated by the host is does not halt their growth by changing their structure or components. E.g: an antibiotic that affects the wall-building mechanism of the bacteria, such as men.in penicillin, cannot affect bacteria that do not have a cell wall. (e.g: mycoplasma) siege Antibiotic resistance occurs when bacteria evolve to evade the effect Acquired Resistance: Is of antibiotics through multiple different mechanisms. Bacteria can obtain the ability to resist the activity of a particular antimicrobial agent to which it was previously susceptible. Bacteria can acquire resistance through a new genetic mutation that helps the Resistance is a property of the microbe, not a person or other bacterium survive or by getting DNA from a bacterium that already is resistant. organism infected by a microbe An example is Mycobacterium tuberculosis resistance to rifamycin EEEE.IE  How bac resist antibiotic The mechanisms of antibiotic resistance : The mechanisms of antibiotic resistance : 1 A. Genetic alterations leading to drug resistance: 1. Spontaneous mutations in DNA: a 7 chromosomal alteration may occur by insertion, deletion or substitution of one or more nucleotides within the genome (vertical gene transfer) An example is the emergence of rifampin-resistant Mycobacterium tuberculosis when rifampin is used as a single antibiotic. 2. DNA transfer of drug resistance: B DNA transfer from one bacterium to another Resistance properties are often encoded in on extrachromosomal plasmids DNA can be transferred by transduction, transformation or bacterial conjugation c s The mechanisms of antibiotic resistance : The mechanisms of antibiotic resistance : C. Enzymatic activation: 2 B. Altered expression of protein in drug-resistant organisms: 3 Some bacteria can develop enzymes that destroy or inactivate the Modification of target sites: antimicrobial agent Example: S.pneumoniae resistance to B-lactam drugs involves alterations in one or more of the major bacterial penicillin binding proteins resulting in decreased binding of the antibiotic to its target Decreased accumulation of the drug: Example: gram-negative bacteria can alter the number and the structure of the porins in their outer-membrane Expression of efflux pump (encoded on chromosomes & plasmids) These drug efflux pumps for xenobiotic compounds have a broad substrate specificity and are responsible for decreased drug accumulation in multidrug-resistant cells.  The mechanisms of antibiotic resistance : C. Enzymatic activation (cont): Example of antibiotic-inactivating enzymes include: 1. B-lactamase: hydrolytically inactivate the B-lactam ring of penicillins and cephalosporins and related drugs: Extended spectrum KPC (Klebseilla B-lactamase pneumonia TEM-1: AmpC: inhibitor ESBL: carbapenemases): plasmid-encoded B- Chromosomally Degrade all B- Plasmid encoded. lactamase encoded and lactams except Degrade all B-lactams Resistance to inducible carbapenem and and carbapenems ampicillin and Mutant strains that sometimes B- lactam/B-lactamase Bacteria that express amoxicillin express large amount KPC often encode of this enzyme are inhibitor resistance to other resistant to All B- antibiotics classes lactam antibiotics making treatment except carbapenems exceedingly difficult 2. acetyltransferases: that transfer an acetyl group to the antibiotic inactivating drugs such as chloramphenicol or aminoglycosides 3. esterase: that hydrolyse the lactone ring of macrolides