Antimicrobial Resistance and AOM BIOMED exam

Antimicrobial resistance (AMR)

Microorganism survives/grows despite an antimicrobial concentration that would normally inhibit or kill a susceptible organism (antibiotics, antivirals, antifungals)

Intrinsic resistance

Organism is naturally resistant due to its normal structure/function (e.g., Pseudomonas aeruginosa)

Acquired resistance

Previously susceptible organism becomes resistant by acquiring resistance genes (e.g., MRSA)

Which type of resistance drives the current AMR crisis?

Acquired resistance (though most bacterial resistance overall is intrinsic)

Drug inactivation/modification

Bacterial enzyme destroys or modifies the drug (e.g., β-lactamase breaks the β-lactam ring of amoxicillin; H. influenzae, M. catarrhalis)

Active efflux (resistance)

Efflux pumps pump drug out of the bacterium → ↓ intracellular concentration (e.g., fluoroquinolone resistance)

Decreased permeability (resistance)

Drug has difficulty entering bacterium (e.g., P. aeruginosa low membrane permeability)

Target site modification

Drug's binding target changes → ↓ binding and effect (altered PBPs in MRSA/DRSP; D-Ala-D-Ala → D-Ala-D-Lactate in VRE)

Gene mutation (resistance)

Changes in bacterial DNA alter a drug target or resistance mechanism (e.g., gyrA mutation → fluoroquinolone resistance)

Horizontal gene transfer

Bacteria acquire resistance genes from another organism (e.g., plasmid-mediated β-lactamase genes)

Cross-resistance

Resistance to one drug results in resistance to similar drugs

Multidrug resistance (MDR)

Resistance to multiple antimicrobial classes → fewer treatment options

Genetic vs. functional resistance mechanisms

Gene mutation and horizontal gene transfer = how resistance is acquired; inactivation, efflux, decreased permeability, and target modification = how the bacterium blocks the drug

Antimicrobial stewardship

Using antimicrobials appropriately to optimize treatment while limiting resistance

Stewardship "rights"

Right drug, right dose, right route, right duration (and only use when clinically indicated)

Key findings of acute otitis media (AOM)

Fever, ear pain/fussiness, ear tugging, erythematous bulging tympanic membrane, purulent middle-ear fluid, poor TM mobility

Most common bacterial pathogen in AOM

Streptococcus pneumoniae

Other AOM pathogens

Haemophilus influenzae and Moraxella catarrhalis (may produce β-lactamase)

Augmentin

Amoxicillin + clavulanate

Amoxicillin

β-lactam antibiotic

Clavulanate

β-lactamase inhibitor, NOT an antibiotic; protects amoxicillin from β-lactamase

Why is clavulanate added to amoxicillin?

β-lactamase would break amoxicillin's β-lactam ring; clavulanate inhibits it, extending amoxicillin's activity against β-lactamase-producing bacteria

Augmentin counseling: side effect

Diarrhea is common, more than with amoxicillin alone

Augmentin counseling: pediatric AOM course

10 days

Augmentin suspension storage

Refrigerate and discard after 10 days (clavulanic acid is less stable in aqueous solution than amoxicillin)