2. Antibiotic Resistance
By:
E. Salehifar
Faculty of Pharmacy
Department of Clinical Pharmacist

3. Suppressed Immune Systems
Antibiotic Usage
Transplants
Dialysis
Suppressed Immune Systems
Joint Replacements

4. Antibiotic Overuse Overprescribing Continuous use in livestock feed
Humans = 30% antibiotic use
Animals = 70%

5. Three possible outcomes after antibiotic use:
Death (Bacteriocidal)
Growth Inhibition (Bacteriostatic)
Resistance

7. The most challenging MDROs in Healthcare Highly Intelligent!
Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant enterococcus (VRE)
Extended-spectrum beta-lactamase-producing bacteria (ESBLs)
Carbapenem-resistant enterobacteriaceae (CRE)
Multi-drug resistant Acinetobacter baumanii (MDR-A)

8. Carbapenem-resistant enterobacteriaceae (CRE)
Significantly limited treatment options for life-threatening infections
No new drugs are under development for gram-negative infections
Resistance mechanisms (carbapenemases) spread readily via plasmids
Co-resistance to other agents is common

12. AG-modifying enzymes

14. Mechanisms of Resistance
Drug inactivation or modification
β-lactamases
Klebsiella pneumoniae carbapenemases (KPCs)
New Delhi metallo-β-lactamase (NDM) carbapenemases
originally identified in Sweden in 2008 and have spread worldwide rapidly
Adding of acetyl or phosphate group to a specific site on the antibiotic → ↓ its ability to bind to the cites of action

15. Mechanisms
Beta-lactam antibiotics permanently inactivate PBP (transpeptidase) leads to inhibition of peptidoglycan synthesis
MRSA:
expresses a PBP that does not allow the antibiotic into its active site

16. Mechanisms of Resistance
Alteration of target- or binding site
Alteration of PBP
MRSA and other penicillin-resistant bacteria.
Ribosomal protection proteins
binding of the ribosomal protection proteins to the ribosomes of the bacterial cell → conformational changes
Alteration of metabolic pathway
Some Sulfonamide-resistant bacteria do not require PABA
Resistant MO uses preformed folic acid
Efflux pump antibiotics
FQs  resistance, AGs, Tetra, Pen, Macrolides

17. Resistant Genes Horizontal Gene Transfer
Plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase
Point mutations (1 in 108 per chromosomal replication)
mutations at key sites in DNA gyrase or topoisomerase IV

18. Horizontal Gene Transfer
that encode a beneficial microbial process are often under positive selection but also

19. To limit the spread of Resistance
Prudent antimicrobial prescribing
Surveillance
C&S tests (sampling, transport, kits, method, interpretation)
DUE studies
RUD committee, D&C committee
Infection control