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Antibiotic Resistance

Antibiotic Resistance. By: E. Salehifar Faculty of Pharmacy Department of Clinical Pharmacist. Antibiotic Usage. Transplants. Dialysis. Suppressed Immune Systems. Joint Replacements. Antibiotic Overuse. Overprescribing Continuous use in livestock feed. Humans = 30% antibiotic use.

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Antibiotic Resistance

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

  2. Antibiotic Usage Transplants Dialysis Suppressed Immune Systems Joint Replacements

  3. Antibiotic Overuse • Overprescribing • Continuous use in livestock feed Humans = 30% antibiotic use Animals = 70% https://amr-review.org/file/327

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

  5. The most challenging MDROs in HealthcareHighly Intelligent! • Methicillin-resistant Staphylococcus aureus(MRSA) • Vancomycin-resistant enterococcus (VRE) • Extended-spectrum beta-lactamase-producing bacteria (ESBLs) • Carbapenem-resistant enterobacteriaceae (CRE) • Multi-drug resistant Acinetobacterbaumanii (MDR-A)

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Horizontal Gene Transfer

  12. 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

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