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)

Effects of some Antibiotics

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+Antibiotics Accumulation in Liver Penicillin family > mostly “liver friendly” very often allergic reaction

RESEARCH WORK

ACQUIRED ANTIBIOTIC RESISTANCE GENES: AN OVERVIEW Mechanisms of Resistance Genes responsible for them

Mycobacterium gene  aac(2)-Ib ACT 588 nt Mycobacterium gene  aac(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 Tn 1546, 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 SCC mec, 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 vanA gene 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 dipeptide terminus 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

“To not use too much so that the bacteria can become immune to the antibiotics and become Superbacteria”