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 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 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”