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Things to be discussed. Multi resistance antimicrobials Effects of some Antibiotics Research article Case study Future Horizons. Multidrug resistance (MDR).
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Things to be discussed • Multi resistance antimicrobials • Effects of some Antibiotics • Research article • Case study • Future Horizons
Multidrug resistance (MDR) • MULTIPLE DRUD RESISTANCE OR MULTI DRUG RESISTANCE IS A CONDITION THAT ENABLES A DISEASE CAUSING AGENT TO DEVELOP RESISTANCE AGAINST CHEMICAL DRUGS ( ANTIBIOTICS)
Mdro’S (resistant TO One or more Classes of antimicrobial agents) • Methicillin resistant Staphylococcus aureus (MRSA) • Vancomycin resistant enterococci (VRE) • Vancomycin resistant Staphylococcus aureus (VRSA) • Extended Spectrum beta-lactamase producing Enterobacteriaceae (ESBL)
Tetracycline family (Oxytetracycline, Doxycyline) • Erythromycin (Erythromycin Estotate, Erythromycin ethylsuccinate) • Chloramphenicolum family(Chloramphenicol Palmitate, Thiamphenicol) • Penicillin family(: Benzylpenicillin,Ampicillin Sodium, Amoxicillin)
Liver( Function------->Dysfunction • The liver has very complicated functions • one of the most important is the detoxification of drugs such as antibiotics and its metabolites. BUT • Some antibiotics can cause allergic reactions while others can cause direct damage to their liver, which can be quite severe in patients with chronic liver disease.
Tetracycline family----------> jaundice, fever, and fatty liver • Erythromycin family-------------> cholestasis (bile retention) elevation of liver enzymes, Nausea • Chloramphenicolum family------------> WBC and RBC counts drop, Glucoronic Acid+AntibioticsAccumulation in Liver • Penicillin family-----------------> mostly “liver friendly” very often allergic reaction
Acquired antibiotic resistance genes:an overview • Mechanisms of Resistance • Genes responsible for them
Mycobacterium gene aac(2)-Ib ACT 588 nt • Mycobacterium geneaac(2)-Ic ACT 546nt • Enterobacter gene aph(3)-Ib PHT 801nt
Staphylococcus gene apmA ACT 822nt • Staphylococcus gene lsa(B) orf3 Efflux 1,479nt • Enterococcus gene tet(M) Ribosomal protection 1,920 nt
The first case of VRSA involved a 40-year-old woman • from Michigan who was undergoing dialysis, diabetes mellitus, hypertension, peripheral vascular disease, chronic renal failure • During the last hospitalization, the patient developed MRSA bacteremia • a number of catheterizations during this time and received a • conjugal transfer of plasmid DNA, giving rise to the VRSA. • conjugative plasmid into which the transposon Tn1546, containing vanA resistance
Methodology • Genetic analysis • Isolation &Detection • Mobile genetic elements • Conjugate Transposons • Conjugative Plasmids
The Acquisition of 2 resistance genes, • resulted in an S aureus strain that was highly resistant to both oxacillin and Vancomycin. • mobile genetic element called SCCmec, which contains the mecA resistance gene.44 • The mecA encodes PBP2a, a new penicillin binding • protein with decreased affinity for oxacillin and most other -lactam drugs.
High-level Vancomycin resistance • occurred because of expression of vanAgene • associated with alteration of the Vancomycin-binding site in the cell wall • Vancomycin interferes with bacterial wall synthesis by binding with the terminal D-alanine-D-alanine • Expression of vanA and other genes ,changes the dipeptideterminus from D-alanine-D-alanine to D-alanine-D-lactate
The continued evolution of resistance to antibiotics has led to wide ranging consultation at National and International levels as to how to; • limit the spread of antibacterial resistance • the development of new antibiotics to help redress the balance of resistance Vs available antibiotics
Role of molecular biology • Genomics • Proteomics • Transcriptional profiling
BEWARE ! “To not use too much so that the bacteria can become immune to the antibiotics and become Superbacteria”