Minimum inhibitory and bactericidal concentrations

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Minimum Inhibitory and Bactericidal ConcentrationsMIC is lowest concentration that prevents growth in vitroSerial dilutions of chemical in suitable growth medium used; cultures added, incubated, examined for turbidityInhibition does not necessarily mean successful treatment; level may not be achieved in person’s bloodMicrobes with MIC between susceptibleand resistantare termed intermediateMBC is lowest concentration that kills 99.9% of cells in vitro; determined from plate count from MICTechniques precise but labor-intense, expensiveMinimum Inhibitory Concentration (MIC)Conventional Disc Diffusion MethodKirby-Bauer disc diffusion testroutinely used to determine susceptibility of bacterial strain to antibiotics
Standard concentration of strain uniformly spread on agar plate; discs containing different antibiotics placed on surfaceDrugs diffuse outward, establish gradientResulting zone of inhibition compared with specially prepared charts to determine whether strain is susceptible, intermediate, or resistantDrug characteristics must be taken into account (for example molecular weight, stability, amount)Commercial Modifications of Susceptibility TestingLess labor-intensive, often faster resultsOne automated system determines growth rate via turbidity in cards, interprets results to determine MICs in 6–15 hoursE test is modification of disc diffusion test, uses strip with gradient of antibioticIntersection of zone of inhibition indicates MICMeasuring Concentration of Antimicrobial Drug in Blood or Other Body FluidsSome toxic; levels must be monitored to ensure safetyDiffusion bioassay compares known concentrations with patient samplesCan produce standard curveComparison yields concentration 20.5. Resistance to Antimicrobial MedicationsIncreasing use, misuse selects for resistant microorganismsOnly 3% of Staphylococcus aureusoriginally resistant to penicillin G; now more than 90% are resistantHundreds of tons used each yearAntimicrobial resistance alarmingImpact on cost, complications, and outcomes of treatmentDealing with problem requires understanding of mechanisms and spread of resistanceMechanisms of Acquired ResistanceAntibiotic-Inactivating EnzymesPenicillinase, chloramphenicol acetyltransferase
Alteration in Target MoleculeMinor structural changes can prevent bindingPBPs (β-lactam antibiotics), ribosomal RNA (macrolides)Decreased Uptake of the Medication Changes in porin proteins of outer membrane of Gram-negativesMechanisms of Acquired Resistance (cont…)Increased Elimination of MedicationEfflux pumps remove compounds from cellIncreased production of pumps allows faster removalStructural changes can influence range of antibioticsResistance of this type particularly worrisome; might allow resistance to multiple antibioticsAcquisition of ResistanceSpontaneous Mutations Occur during replicationHappen at low rate but can have significant effect

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