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98 Cards in this Set
- Front
- Back
What is the procedure to empiric therapy?
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Clindamycin + gentamicin(effective against gram-(+) or imipenem/cilastin(single broad-spectrum antibiotic) ->culture bug -> use specific drug last
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What are the drugs used in Empiric therapy?
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Clindamycin + gentamicin or imipenem/cilastin
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Define: chemotherapy
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The use of chemical s against invading organisms (invading bacteria); NOTE: term is used for both treatment of infection and cancer
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Define: antibiotic
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Chemical that is produced by a microorganism and has the ability to harm other microbes
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Define: selective toxicity
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The ability of a drug (chemical) to injure a target cell or organism without injuring other cells or organisms that are in intimate contact
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How do u select the most appropriate anti-microbial agent?
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1. Organisms identity and its sensitivity to a particular agent, 2. site of infection, 3. safety of the agent, 4. patient factors, 5. cost of therapy
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Define: empiric therapy
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Use of antimicrobial agents before the pathogen is known; based on experience; justified if evidence demonstrates that early intervention will improve outcomes
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What is the most commonly used method to test susceptibility to antibiotics
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Disk diffusion test - disks containing antibiotics are placed on culture dishes inoculated w/the microorganism to be tested. Growth = resistance to bugs, no growth = sensitivity to bug
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Define: selective toxicity
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Kill the germs not the patient -> achieved by disruption of cell wall, protein synthesis, enzyme unique to bacteria
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What are the characteristics of selective toxicity?
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1. Unique target must be present in pathogen + absent in host, 2. Target must be structurally different in pathogen vs host, 3. Target must be more important in pathogen than in host
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What is the MOA of disruption of the bacterial cell wall
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Bacteria are encased in a rigid cell wall -> if disrupted bacteria would absorb water, swell, burst
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Which drugs target microbes cell wall -> thus promoting bacterial lysis?
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Penicillin and cephalosporins; b/c mammalian cells have no cell wall -> drugs directed at this structure do not affect the host
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What is the MOA of inhibition of an enzyme unique to bacteria
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Bacteria need to produce folic acid denovo -> sulfonamides inhibit bacteria production -> no PABA -> folic acid -> no division
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What drug inhibits bacterial de novo generation of folic acid?
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Sulfonamide
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What is the combination of drugs to target folic acid production?
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Sulphonamides(inhibits dihydropepteroate synthase) + trimethoprim(inhibits dihydrofolate reductase)
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What drugs cause disruption of cell wall membrane?
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Amphotericin B, ketoconazole
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What drugs cause bacteriostatic inhibitors of protein synthesis?
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Clindamycin, erythromycin, tetracyclines
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What drugs cause interference w/synthesis of bacterial DNA or RNA
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Fluoroquinolones, rifampin
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What drugs are anti-metabolites
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Flucytosine, sulfonamides, trimethoprim
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What drugs are viral enzyme inhibitors
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Acyclovir, zidovudine, saquinavir, indinavir
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What drugs are mycolic acid synthesis?
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Isoniazid
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What drugs have unknown mechanisms
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Amntadine, ethambutol, pyraziamide
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What drug is involved in the blockage of DNA twisting?
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Fluoroquinolones - thus blocks DNA gyrase from working
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What is the MOA of "unique" selective targeting?
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Drug targets genetic or biochemical pathway that is unique to pathogen(ie bacterial cell wall synthesis inhibitors)
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What is the MOA of "selective" selective targeting?
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Drugs targets protein isoform that is unique to pathogen(ie DHFR inhibitor)
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What is the MOA of "common" selective targeting?
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Drug targets metabolic requirement that is specific to pathogen(ie 5-Fluorouracil)
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Drugs that affect growth
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Bacterial static(tetracycline)
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Drugs that kill off the bactera
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Bacterialscidal(penicillin)
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What are the bactericidal drugs that we need to know?
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1. Bacitracin, 2. beta-lactams, 3. quinolones, 4. aminoglycosides, 5. polymyxins, 6. rifampin
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What are the bacteriostatic drugs that we need to know?
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1. Tetracycline, 2. sulfonamide, 3. trimethoprim, 4. chloramphenicol, 5. macrolide, 6. novobiocin, 7. clindamycin
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Define: minimum inhibitory concentration
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Anti-microbial should be present in concentrations such that it can either inhibit bacterial growth
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Define: minimum bactericidal concentration
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Kill the organism
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What are 3 factors that determine susceptibility and resistance of microorganisms to antimicrobial agents?
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1. Failure of drug to reach its target, 2. drug inactivation, 3. target alteration
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What is the MOA of entry for slow drug entry into a bacteria?
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Slow drug entry into a cell = via PORINs
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What is the MOA of gentamicin
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Targets ribosome -> actively transported across the cell membrane
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What is the MOA of resistance of gentamicin?
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1. Bacteria makes resistance by mutating the active transport mechanism of the drug, 2. anaerobic conditions slows entry into the cell
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What is the MOA of resistance of tetracyclines, chloramphenicol, fluoroquinolones, macrolides, beta-lactam antibiotics.
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Bacterial efflux pumps -> transports drugs out
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How do bacteria prevent entry of a drug into the cell?
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1. Mutation of porin causes blockage thus drug cant get in, 2. mutation in transport mechanism(active transport - gentamicin, efflux pump - tetracycline)
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How do lower urinary tract antibiotics get to its target site?
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The antibiotic is NOT metabolized in the body -> goes thru the blood -> into urine (intact) -> has effect
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How do bacteria inactivate aminoglycosides + beta-lactam antibiotics?
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Production of enzymes that modify or destroy the antibiotic (aka anti-penicillin protein)
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What drug is a prodrug that requires a bacterial enzyme to activate the drug?
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Isoniazid - mycobacterium tuberculosis activates the drug inside the bacteria(the bug is its own worst enemy)
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What is the MOA of Fluoroquinolones resistance?
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Utilizes mutation of natural target - gyrase mutation
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What is the MOA of macrolide and tetracycline resistance?
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Target modification - ribosomal protection
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What is the MOA of resistance of staphylococcal resistance to methicillin?
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Acquired resistant form of the susceptible target -> caused by production of low-affinity penicillin binding proteins(ie penicillin cant work on its target)
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Define: vertical acquisition of drug resistance
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Passage of trait to daughter cells
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Define: horizontal acquisition of drug resistance
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Between individual s by PLASMID EXCHANGE
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What are the advantages of horizontal gene transfer in bacteria?
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1. Avoids lethal mutation of essential genes, 2. level of resistance is higher -> caused by incremental change, 3. genes can be transferred to susceptible cells easily
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What is the MOA of streptomycin resistance?
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Ribosomal mutation
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What is the MOA of rifampin resistance?
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RNA polymerase mutation
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What is the MOA of linezolid resistance?
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Ribosomal RNA mutation
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How does high level resistance to a drug emerge?
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1. Sequential series of mutations(plasmids), 2. mutation that confers high-level resistance in a single step
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What is horizontal gene transfer
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Plasmid transfer of resistant genes
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Define: conjugation
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Direct transfer of resistant genes by cell-to-cell contact through a sex pilus or bridge(occurs in gram (-) bacilli + enterococci + staphylocicci)
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What is the requirements in bacteria that can under conjugation?
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R-factor
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How is antibiotic resistance is enhanced by natural selection
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Top selection (mixed resistance population) -> middle selection (only the strong survive) -> last selection -> only the strong replicate
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What is strep pneumoniae resistant to?
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Penicillin
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What is e coli resistant to?
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Fluoroquinolone
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What is staph aureus resistant to?
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vancomycin
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What is the problem w/broad spectrum antibiotics
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Sine broad spectrum antibiotics kill off more competing organisms than do narrow-spectrum drug, emergence of resistance is facilitated most by the broad-spectrum drugs
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Define: superinfection
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New infection that appears during the course of treatment for a primary infection -> new infection can develop b/c antibiotic use can eliminate the inhibitory influence of normal flora -> allowing a second infectious agent to flourish (common in broad-spectrum agents)
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How do you select antibiotics
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1. Identify organism, 2. drug sensitivity, 3. host factors
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What type of drugs are used to keep bacteria at bay in AIDS patients?
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Bactericidal
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How does meningitis impede drug access?
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BBB
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How does endocarditis impede drug access?
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Bacterial vegetation in the heart are difficult to penetrate
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How does infected abscesses impede drug access?
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Poor vascularity and the presence of pus and other material
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What are the 3 ways to get a drug across the BBB?
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1. Drug that readily crosses the BBB, 2. inject into subarachnoid space, 3. remove pus that hinders drug access
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Why do the elderly have high drug sensitivity?
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Reduced rates of drug metabolism + excretion -> leads to accumulation of antibiotics to toxic levels
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Why do neonates have high drug sensitivity?
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Poorly developed kidney and liver function -> eliminate drugs slowly
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What is the side effect of sulfonamides in newborns?
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New borns + sulfonamides = kernicterus(high levels of bilirubin)
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What is the side effect of tetracyclines in new borns?
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Binds to developing teeth -> causes discoloration of the teeth
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What is the side effect of gentamicin during pregnancy?
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Pregnancy + gentamicin -> irreversible hearing loss
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What is the side effect of anti-microbial drugs during pregnancy?
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Pregnancy + antimicrobial -> crosses placenta -> posing a risk to the developing fetus
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What is the side effect of tetracyclines during pregnancy?
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Pregnancy + tetracycline -> hepatic necrosis, pancreatitis, renal damage
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What is the side effect of sulfonamides in breast milk?
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Sulfonamide + breast feeding -> enters breast milk
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Which antibiotics have a chance of severe allergic reaction
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1. Penicillin, 2. sulfonamide, 3. trimethoprim, 3. erythromycin
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What is the side effect of sulfonamides in G6PD deficient people?
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Hemolysis
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What are the reasons to use anti-biotic combinations?
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1. Initial therapy of severe infection, 2. mixed infection, 3. prevention of resistance, 4. ↓ toxicity, 5. enhanced anti-bacterial action
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What are the 3 possible effects by using 2 antibiotics in combination?
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1. Additive, 2. potentiative(aka synergistic), 3 .antagonistic(static agent is antagonistic to cidal agent
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What is the MOA of an additive response?
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Antimicrobial effect of combination = the sum of the effects of the two drugs alone(ie 2 bacteriostatic agents w/same MOA)
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What is the MOA of a potentiative (synergistic) response?
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Effect of the combination is greater then the sum of the effects of the individual agent(shows a 4x ↑ in antibacterial activity aka ↓ in MIC by 1/4)
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What are the 3 mechanisms of antibiotic synergism?
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1. Blockade of sequential steps(trimethoprim + sulfamethoxazole, 2. inhibition of enzyme(beta-lactam + beta-lactamase inhibitor sulbactam), 3. enhancement of AB uptake(penicillin ↑ uptake of aminoglycoside)
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Define: mixed infections
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Infections that may be caused by more than one microbe -> common in brain abscesses, pelvic infection, and infections from perforation of abdominal organs.
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How does the combination of flucytosine + amphotericin B work?
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Decreased toxicity -> treats fungal meningitis (prevents risk of amphotericin-induced damage to kidney)
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How does the combination of penicillin + aminoglycoside work?
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Enhanced antibacterial action - penicillin weakens bacterial wall + aminoglycoside suppresses protein synthesis
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When do u use prophylactic antibiotics?
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Surgery, congentital abnormalities, neutropenia
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What are the misuses of antibiotics
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1. Viral infection, 2. fever of unknown origin, 3. improper dosage
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What group of drugs is amoxicillin in?
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Penicillins
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What group of drugs is tetracycline in?
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Tetracyclines
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What group of drugs is streptomycin in?
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Aminoglycosides
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What group of drugs is levofloxacin in?
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Quinolones
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What group of drugs is cefaclor in?
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Cephalosporins
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What group of drugs is erythromycin in?
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Macrolides
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What is the MOA of amoxicillin?
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Binds to Penicillin binding proteins
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What is the MOA of tetracycline?
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30S ribosome
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What is the MOA of sterptomycin?
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Affects protein synthesis
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What is the MOA of levofloxacin?
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DNA gyrase inhibitors
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What is the MOA of cefaclor?
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Protein synthesis
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What is the MOA of erythromycin?
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50S ribosome
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