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67 Cards in this Set
- Front
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Antibiotics definition
Antimicrobial definition |
ATB = natural compound produced by bacteria or fungi to suppress growth of other microorganisms
Antimicrobial = synthetic agents to suppress growth of other microorganisms |
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Drugs that work by inhibiting cell wall synthesis:
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- Bacitracin
- Beta Lectams - Vancomycin - Cycloserine - Cephalosporins |
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Drugs that work by inhibiting DNA replication:
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- Quinolones
- Nitroimidazoles |
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Drugs that inhibit DNA-Dependant RNA polymerase:
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- Rifampin
- Rifabutin |
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Drugs that inhibit Folic Acid Synthesis:
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- Trimethoprim
- Sulfonamides - Sulfones |
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Drugs that inhibit Cell membranes:
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- Polymyxins
- Daptomycin |
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Drugs that inhibit Protein Synthesis:
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- Aminoglycosides
- Macrolides - Ketolides - Lincosamides - Streptogramins - Tetracyclines - Glycyclines - Chloramphenicol - Oxazolidinones |
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What factors influence selection of antimicrobial agent?
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1. Identification of Organism
2. Microbial susceptibility 3. Bactericidal vs Bacteriostatic 4. Bug-Drug Specificity 5. Knowledge of patient |
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What factors are increasing the resistance to ATBs?
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- Indiscriminany use (against viruses, or because of environmental factors)
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What tests can you do for sensitivity testing?
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- disk diffusion
- microdilution - E-test |
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Explain disk diffusion
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Bacteria is placed on a dish, different spots of either diefferent ATBs or different strengths are placed on the dish and you look to see how far the ring goes out from each
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What is MIC? MBC?
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MIC - the minimum concentration that is needed to stop any growth
MBC - the minimum concentration needed to kill the bacteria |
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What would be a reason to use a bactericidal ATB instead of a bacteriostatic ATB?
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Host immune's system; it needs to be working to be able to clear the body of the bacteria that is stopped from growing
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Common side effect of tetrayclines:
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can bind to calcium and discolor teeth and bones (don't use in children)
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What causes grey baby syndrome?
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Chloramphenicol
infants can't conjugate it, so they turn grey |
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Explain time dependent killing
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You need to maximize time spent above the MIC; the conecntration above that doesn't matter, as long as it is above MIC for as long as possible
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Explain concentration dependent killing
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You can give one dose once a day because the ATB will get into th ebacteria anc continue to kill, even if levels drop
*Do not need to monitor levels! |
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Appropriate uses of Combination ATB therapy
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- TX of life threatening infection (with unknown organism)
- polymicrobial infections - enhanced antimicrobial activity (AGs + penicillins for P. Aerug) - Tx resistant strains - Lower doses of agents (less toxicity) - may reduce resistant strains emerging (not proven) |
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Mechanisms of Resistance
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1. Selection - strongest bacteria survive
2. Enzymes to destroy active drug 3. Change in permeability to drug 4. Change in efflux pathway 5. Change in affinity of site of active drug 6. Altered metabolic pathways 7. Altered enzymes with less affinity |
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Examples of bacteria that produce enzymes to destroy drug
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Penicillinases
Carbepenemases Cephalosporinases |
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Examples of bacteria that change permeability
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Beta lactamases with porins
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Drugs affected by efflux changes
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Tetracyclines
Chloramphenicol Macrolides |
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Drugs affected by changes in affinity of site of drug or with altered enzymes with less affinity
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protein synthesis inhibitors
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Drugs that are affected by changes in altered metaolic pathways
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Sulfonamides
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Origins of resistance
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- Spores in a dormant stage
- A change in target structure after repliations - Genetic changes |
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What genetic changes can lead to resistance?
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- Mutational resistance (chromosomal change)
- Conjugation (passed on through plasmids) - Transduction (phages can transfer DNA) - Transformation (free DNA is absorbed) |
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What bacteria commonly shows resistance by conjugation?
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gram negative bacteria
thwarts Vancomycin |
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What bacteria commonly shows resistance by transduction?
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S. aureus
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What is the main difference between gram negative and positve bacteria?
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Gram negative have THIN cell walls, but two cell membranes
Gram positive have THICK cell walls and only one membrane |
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Gram + stains ___
Gram - stains ___ |
- pink
+ purple |
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Cell wall is made of ____strands of ___ and ___
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Peptidoglucan strand of N-acetylglucosamine and N-acetylmuramic acid
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Transpeptidases do what?
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cross link adjacent strands to give lattice structure
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What are PBP's?
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Penicillin Binding Proteins
enzymes (transpeptidase, carboxypeptidase, trransglycosylase) responsible for maintenance and regularion of wall |
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Beta lactams general MOA
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form covalent bonds with PBP transpeptidases to inhibit activity
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Vancomycin general MOA
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binds end of polypeptide chain to prevent elongation
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Bacitracin general MOA
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Inhibits lipid carrier bringing strand out of cell
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Beta Lactam agents:
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- Penicillines
- Cephalosporins - Monobactams - Carbapenems - Beta Lactamase inhibitors |
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Agents that work on cell wall synthesis:
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- Beta lactams
- Vancomycin - Daptomycin - Fosfomycin - Bacitracin |
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Beta Lactam general notes
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- ring is essential for activity
- bactericidal inhibit both gram + and - |
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Natural Penicillins (2)
work against? |
Pen G (IV) and Pen V (oral) against streptococcal and pneumococcal
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Penicillinase Resistant Penicillins (4) work against?
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- Methacillin
- Dicloxacillin - Nafcillin - Oxacillin against penicillinase producting staphylococcal |
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Broad Spectrum Penicillins (5) work against?
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- Ampicillin
- Amoxicillin - Bacampicillin - Amoxicillin + Clavulanic acid - Ampicillin + Sulbactam against S. pyrogenes, S. penuemoniae, H. influenzae |
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Antipseudomonal Penicillins (4) against?
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- Piperacillin
- Ticarcillin - Ticarcillin + Clavulanic acid - Piperacillin + Tazobactam against P. aeruginosa, Proteus Enterobacter |
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PKinetics of Penicillins
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oral availability (except Pen G), acid stability
Absorption DECREASED by food limited lipid solubility - distributes well into tissues Eliminated by active tubular secretion |
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A/E of Penicillins
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- Allergies (environmental exposure)
- CNS irritation (seizures) - GI irritation (diarrhea) |
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What mechanisms of resistance inhibit Penicillins?
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- Production of beta lactamases
- Add/Lack of specific binding to PBPs - Cell membrane doesnt lyse after binding - Organisms without cell wall aren't affected by Penicillins (mycoplasma) |
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Misuse of Penicillins can lead to?
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- selection of resistant strains
- super infections - fungal or C. Difficile - Transfer of beta lactamase to other organisms |
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Cephalosporin general notes:
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- structurally similar to penicillins
- usually not 1st line - each generation increases gram NEG activity - cross sensitivity with penicillins - poor oral absorption |
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1st generation Cephalosporins:(4) against?
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- Cefazolin
- Cephalexin - Cephradine - Cefadroxil against streptococci, S. Aureus |
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2nd gen Cephalosporins (4) against?
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- Cefuroxime
- Cefprozil -Cefmetazole - Loracarbef against E Coli, Klebsiella, proteus, H. influenzae, moraxella |
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3rd gen Cephalosporins (9) against?
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- Cefotaxime
- Cefpodoxime - Cefibuten - Cefdinir - Cefditoren - Ceftizoxime - Ceftriaxone - Cefoperazone - Ceftazidime against Enterobacteriacae, p aeruginosa, serratia, nisseria gonorrhea, pseudomonas |
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4th gen Cephalosporins (1) against?
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- Cefepine
**Is lactamase resistant against Enterobacteriacae, p aeruginosa, serratia, nisseria gonorrhea, pseudomonas (same as 3rd) |
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5th gen Cephalosporins (1) against?
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- Ceftobiprole
against MRSA, enterococcus pseudomonas |
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A/E of Cephs
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- allergy (CI in penicillin allergy)
- Nephrotoxic - Bleeding disorders b/c methothiotetrazole ring interferes with Vit K |
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Carbapenems (4)
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Imipenem
Meropenem Ertapenem Dorapenem |
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Carba general notes
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- Broadest spectrum beta lactams
- gram neg, pos, anaerobes, P. aeruginose (not erta) - IV - excreted by kidney |
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Inidications of carbas
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- mixed anaerobic/aerobic abdominal infections
- multi-drug resistant org - serious nocosomal infections (imip, mero) - community infection (erta) - abdominal + complicated UTI (dora) |
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A/E Carbas
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- sensitivty with other beta lactams
- seizures at high doses - anemia, altered bleeding time |
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Monobactam (1) and general notes
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Aztreonam
- against gram NEG, p. aeruginosa - ***NO GRAM POS activity! - Multi-drug resistant org - IV or IM - Renal excretion |
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A/E Monobactams
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- N/V
- Diarrhea - Seizures - bone marrow suppression with long term use - NO cross reactivity with other beta lactams |
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Vancomycin notes
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- For gram POS, MRSA, penicillin-resistant enterococci and streptococci
- IV - reserved for severe infections - Pseudomembranous colitis due to C. Difficile (use Metronidazole) - renal excretion |
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Vacnco A/E:
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- fever, chills, shock
- Redman Syndrome - nephrotoxicity - ototoxicity (with other agents, like AGs or furosemide) |
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Telavancin notes
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- Vanco derivative
- Skin and skin structure probs, MRSA, gram POS and nocosomial pneumonia - MOA: disrupts membranes to depolarize bacteria, AND inhibits cell wall synthesis |
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A/E Telavancin
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- N/V, foamy urine
- decreased renal function - redman syndrome - taste disturbances - may interfere with clotting tests - teratogenic - do preg test before treating - QT prolongation |
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Daptomycin notes
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Cyclic lipopetide
MOA: binds to cell membrane resulting in depolarization and loss of membrane potential and cell death - Broad spectrum gram POS, vanco resistant bacteria, staphylococci, streptococci - IV, adjust for renal def - Infactived by pulmonary surfactant so NOT FOR PNEUMONIA |
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Fosfomycin notes
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MOA: Blocks first step of peptidoglycan synthesis
- single dose tx for uncomp UTI due to E.Coli or enterococci faecalis - concentrated and excreted unchanged in urine A/E: N/V, diarrhea, vaginitis, asthenia |
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Bacitracin notes
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MOA: cyclic polypeptide that blocks lipid carrier molecule to move peptidoglycan to cell wall
- gram POS - use Topically OTC - Nephrotoxicity if systemic use |