Antibiotic Resistance Flashcards
minimum inhibitory concentration (MIC)
lowest concentration that inhibits growth
minimum bactericidal concentration (MBC)
lowest concentration that kills 99.9% of population
susceptible
MIC can be achieved in the body at recommended doses
resistant
MIC cannot be achieved
drug resistance
usually genotypic changes that are retained in the absence of antibiotic; MIC cannot be achieved
tolerance/persistence
transient, dormant variants (not mutants) in the population enabling survival in presence of antibiotic; linked to biofilm formation
mechanisms of resistance
- modification of target so it is insensitive to inhibitor
- duplication or replacement of target enzyme
- efflux pumps
- depression of metabolic agents needed for prodrug
class C serine beta lactamases
inhibit all but carbapenems
class A & D, serine pencillinases/beta lactamases
first discovered in s. aureus shortly after penicillin was introduced
extended spectrum beta lactamases
mutations in penicillinases - resistance to penicillins and cephalosporins; widespread in enterobacteriaceae, pseudomonas, usually plasmid encoded; inhibited by clavulanate
clavulanate
beta lactamase inhibitor
serine carbapenemases
inhibited by clavulanate
class B metallo-beta lactamases (zinc)
cleave all beta lactam antibiotics including carbapenems; inhibited by EDTA but not clavulanate
possible beta-lactam resistance mechanisms
beta lactamase enzymes, reduced cell wall permeability, mutations in PBP to prevent beta lactam from binding
aminoglycosidase resistance mechanisms
acetylation, methylation, or phosphorylation of 30S subunit
anti-folates resistance mechanisms
replacement enzymes
tetracycline resistance mechanisms
efflux pumps
fluoroquinolones resistance mechanisms
altered gyrase/topoisomerase or efflux pumps
elements that mediate antibiotic resistance
plasmids, insertion sequences/transposons, integrons, genetic exchange (conjugation, transformation, transduction)
integrons
genetic unit that includes genes of a site-specific recombination system capable of capturing and mobilizing genes contained in mobile elements (gene cassettes)
multiple antibiotic resistance
conjugation (cell-to-cell contact) allows transferring of resistance to other organisms