Clinical Definition of Antibiotic Resistance ● Minimum Inhibitory Concentration ○ Lowest concentration of antibiotic ○ Intibits visible bacterial growth after 18 hours at 37 C ● Minimum Breakpoint Concentration ○ Chosen concentration (mg/L) of antibiotics ○ Whether a species of bacteria is susceptible or resistant to the antibiotics ● Susce[ptible ○ Organisms should respond to therapy using recommended antibiotics dosage for the given site of infection and species ● Resistance ○ Organism should not be inhibited by concentration achieved with normal dosage Intrinsic Antibiotic Resistance ● Specified b naturally occurring gene found on he bacterial chromosome ○ Cell membrane permeability efflux pump ■ Lack of target site ■ Impermeable outer membrane ● Antibiotic cannot enter ■ Efflux pump expel antibiotic out of the cell ■ Enzyme inactivation ● Limits therapeutic options for treatment form the onset ○ Ampicillin cannot be used to treat P.aeruginosa infection ■ Outer membrane permeability less permeable ■ Ampicillin cannot efficiently penetrate ■ Using Efflux pump, pumps out antibiotics ■ MIC for ampicillin on Pseudomonas is very high ● Large dose is needed to inhibit its growth MIC: Minimum Inhibitory concentration ● Outer membrane ○ Gram-negative bacteria ○ PRovides extra protection ● Porin Channel (pore) ○ A enters cell through porin channel ○ Small molecules to pass through outer membrane ■ Beneficial because buys time for other resistance mechanisms ■ Hydrophilic antibiotics cannot cross the outer membrane of gram negative bacteria ● Peptidoglycan later ○ Between outer and inner membrane ○ A targets penicillin Binding Protein PBP to inhibit cell wall system ○ Bacteria could simply make more PBP to outcompete antibiotics ○ Bacteria could have replication mutation on PBP so antibiotic cannot disable their cell wall ● Antibiotic C/B ○ Fail to enter due to impermeability ○ Enter and removed by efflux ● Efflux pump ○ Resistant mechanism ○ Pump out antibiotics from bacterial cells