Bacterial mechanisms of antibiotic resistance (beta-lactamases, efflux pumps, target modification) with a representative organism for each, distinct from the drug-mechanism focus of the USMLE Antibiotics pharmacology deck.
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- What general reaction do beta-lactamase enzymes catalyze?
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Hydrolysis of the beta-lactam ring, inactivating the antibiotic- Which organism is classically associated with penicillinase production causing penicillin resistance?
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Staphylococcus aureus- Extended-spectrum beta-lactamases (ESBLs) confer resistance to which drug classes?
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Penicillins and cephalosporins (but not carbapenems)- Which two gram-negative organisms are classically associated with ESBL production?
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Escherichia coli and Klebsiella pneumoniae- KPC (Klebsiella pneumoniae carbapenemase) confers resistance to which important drug class?
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Carbapenems- AmpC beta-lactamase is a chromosomally encoded, inducible enzyme most associated with which organism?
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Enterobacter cloacae- Metallo-beta-lactamases require which metal ion cofactor for activity?
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Zinc- NDM-1 is an example of which type of beta-lactamase?
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A metallo-beta-lactamase- What is the mechanism of action of clavulanic acid?
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It inhibits bacterial beta-lactamase enzymes, protecting the co-administered beta-lactam- MRSA resistance to beta-lactams is caused by an altered penicillin-binding protein called ____.
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PBP2a- Which gene encodes the altered penicillin-binding protein responsible for MRSA resistance?
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mecA- Why does PBP2a confer resistance to beta-lactams in MRSA?
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It has low binding affinity for beta-lactam antibiotics- In vancomycin-resistant enterococci (VRE), the vanA gene changes the peptidoglycan precursor terminus from D-alanine-D-alanine to ____.
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D-alanine-D-lactate- Why does the D-Ala-D-Lac substitution reduce vancomycin's effectiveness in VRE?
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Vancomycin binds D-Ala-D-Ala with much lower affinity for D-Ala-D-Lac, so it can no longer block cell wall synthesis- Penicillin resistance in Streptococcus pneumoniae is due to which mechanism (not beta-lactamase production)?
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Altered (mosaic) penicillin-binding proteins with reduced drug affinity
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