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example bacterial pneumonia, severe staphylococcal infections) was grim before availability of penicillin in 1940s•Physicians could identify cause, but only treatment was usually bedrest•Misuse coupled withevolution of microbialresistance threatensthese medications
20.1. History and Development of Antimicrobial MedicationsDiscovery of Antibiotics•In 1928, Alexander Fleming identified mold Penicilliumexcreting compound toxic to Staphylococcus•Named compound penicillin•Showed effective in killing many bacterial species•Unable to purify, he later abandoned research•~10 years later, Ernst Chain and Howard Florey purified, tested compounds in 1941 on police officer with life-threatening Staphylococcus aureusinfection–Patient improved dramatically within 24 hours–Supply of purified penicillin ran out and he later died•WWII spurred research and development; penicillin G was first antibiotic(naturally produced antimicrobial)
20.1. History and Development of Antimicrobial MedicationsDiscovery of Antibiotics (continued…)•Soon thereafter, Selman Waksman purified streptomycin from soil bacterium Streptomyces griseus•Researchers screened hundreds of thousands of microbes for antibiotics•Pharmaceutical companies examine soil samples from around world•Discovered in 1960s that altering structure of penicillin yields new medications
20.2. Characteristics of Antimicrobial MedicationsSelective Toxicity: cause greater harm to microbes•Interfere with essential structures or properties common in microbes but not human cells•Toxicity is relative and expressed as therapeutic index•Lowest dose toxic to patient / dose used for therapy–Penicillin G useful, has high index; interferes with cell wall synthesis, a process not present in humans–Medicationss too toxic for systemic use may be used topicallyAntimicrobial Action•Bacteriostaticchemicals inhibit bacterial growth•Patient’s defenses must still eliminate•Bactericidalchemicals kill bacteria•Sometimes only inhibitory
20.2. Characteristics of Antimicrobial MedicationsSpectrum of Activity•Broad-spectrum antimicrobialsaffect a wide range•Important for treating acute life-threatening diseases–Especially when no time to culture for identification•Disrupt normal microbiota that help in keeping out pathogens•Narrow-spectrum antimicrobialsaffect limited range•Requires identification of pathogen, testing for sensitivity•Less disruptive to normal microbiotaEffects of Combinations•Some medications interfere with each other, are antagonistic•Combinations where one medication enhances are synergistic•Combinations that are neither are additive
20.2. Characteristics of Antimicrobial MedicationsTissue Distribution, Metabolism, and Excretion•Antimicrobials differ in behavior in body•Only some medications cross the brain-blood barrier important in treating meningitis•Some unstable at low pH, must be injected•