Antibiotics: Resistance Flashcards
Intrinsic resistance:
A bacteria, by nature of its innate biology, is not susceptible to an antibiotic (i.e., gram-negatives are resistant to vancomycin, because the molecule is too large to penetrate its outer plasma membrane.)
Acquired resistance:
A bacteria, by alterations in its genetic material, becomes resistant to an antibiotic over time (i.e., staphyloccocus acquires the ability to produce a penicillinase, rendering it resistant to penicillin).
Constitutive resistance:
Resistance mechanism is always present (i.e., outer membrane in gram-negatives is always present).
Inducible resistance:
Resistance mechanism is “turned on” in response to environmental stimuli (i.e., drug efflux pumps).
Mechanisms of acquired resistance:
1) Single nucleotide base-pair mutations (i.e., A to G transition produces resistance to quinolones).
2) Acquisition of plasmids, bacteriophages, and transposons (i.e., multiple resistance mechanisms may be acquired simultaneously)
3) Bacterial conjugation (i.e., resistant bacteria transfers resistance genes to susceptible bacteria)
MIC and MBC:
Minimal inhibitory concentration: usually performed using a liquid medium.
Minimal bacteriocidal concentration: usually performed using a solid medium.
MIC < MBC.
A drug is useful is therapeutic if serum levels of the drug exceed MIC by 4x.
Resistance to PENICILLINS:
Beta-lactamases or altered PBPs.
Resistance to VANCOMYCIN:
Modified cell wall targets.
Resistance to BETA-LACTAMASE INHIBITORS:
Modified beta-lactamases, increased production of beta-lactamases.
Resistance to QUINOLONES:
Mutations in DNA gyrase/topoisomerase
Resistance to RIFAMPIN:
Mutations in RNA polymerase
Resistance to MACROLIDES/LINCOMYCINS:
Ribosomal RNA methylation
Resistance to TETRACYCLINES:
Efflux pumps
Resistance to AMINOGLYCOSIDES:
Aminoglycoside-modifying enzymes
Resistance to TMP-SMX:
Mutations in DHFR
