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Micro CH 13
Antimicrobial Therapy
80
Biology
Undergraduate 2
04/11/2011

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Term
Paul Ehrlich
Definition
coined the term chemotherapy, also discovered salvarsan in 1910 to treat syphilis
Term
Gerhard Domagk
Definition
discovered a red dye (prontosil) in 1935 that inhibits growth of gram + organisms
Term
Ernest Fourneau
Definition
found that antimicrobial activity of prontosil was due to sulfanilamide portion of molecule
discoveries stimulated development of sulfa drugs
Term
Alexander Fleming
Definition
discovered that Penicillin inhibits growth of microorganisms
Term
Chain & Florey
Definition
isolated penicillin and developed methods of mass production
Term
Selman Waksman
Definition
discoverer of streptomycin in the 1940s
Term
chemotherapy
Definition
use of chemical substances to kill pathogenic organisms without injuring the host
Term
chemotherapeutic agent
Definition
any chemical substance used in medical practice
Term
antimicrobial agent
Definition
special group of chemotherapeutic agents used to treat diseases caused by microbes
Term
What does antibiotics literally mean?
Definition
against life
Term
antibiotics
Definition
chemical substance produced by microorganisms which has the capacity to inhibit growth and even destroy bacteria and other microbes in dilute solution
Term
synthetic drugs
Definition
agents synthesized in the lab
Term
semisynthetic drugs
Definition
antimicrobial agents made partly by lab synthesis and partly by microorganisms
Term
What organism caused the Bubonic Plague/Black Death?
Definition
Yersinia pestis
transmitted by rat bites, fleas, etc.
Term
selective toxicity
Definition
must harm the microbes without causing significant damage to the host
Term
toxic dosage level
Definition
a drug causes harm to the host
Term
therapeutic dosage level
Definition
a drug successfully eliminates the pathogenic organism if the level is maintained over a period of time
Term
chemotherapeutic index
Definition
maximum tolerable dose per kg of body weight divided by minimum dose per kg of body weight
Term
spectrum of activity
Definition
range of different microbes against which an antimicrobial agent acts
can be broad or narrow
Term
5 Drug mechanisms of action
Definition
inhibition of cell wall synthesis
disruption of cell membrane function
inhibition of protein synthesis
inhibition of nucleic acid synthesis
action as antimetabolites
Term
antimetabolites
Definition
a substance, similar in structure to normal metabolites, that prevents a cell from carrying out an important metabolic reaction
Term
What are the 2 ways that antimetabolites work?
Definition
by competitively inhibiting enzymes
by being erroneously incorporated into important molecules such as nucleic acids
Term
What is an example of an antimetabolite that competitively inhibits enzymes?
Definition
sulfanilamide, similar to PABA, competitively inhibits enzyme that acts on PABA, so no folic acid can be made
Term
What are 2 examples of metabolites that erroneously incorporate into nucleic acids as analog purines & pyrimidines?
Definition
purine analog vidarabine & pyrimidine analog idoxuridine
Term
Name the 4 antimicrobial agents that inhibit cell wall synthesis.
Definition
Penicillin
Cephalosporins
Carbapenems
Bacitracin
Term
Penicillin
Definition
inhibits cell wall synthesis
used to treat wide variety of infections, mostly gram-positive organisms
Term
Cephalosporins
Definition
inhibit cell wall synthesis
used to treat a wide variety of infections when allergy or toxicity makes other agents unsuitable
Term
Carbapenems
Definition
inhibit cell wall synthesis
used to treat mixed infections, nosocomial infections, and infections of unknown etiology
Term
Bacitracin
Definition
inhibits cell wall synthesis
used to treat skin infections (topical application)
Term
Name the 2 antimicrobial agents that interfere with cell membrane function.
Definition
polymyxins
tyrocidins
Term
Polymixins
Definition
interfere with cell membrane function
used to treat skin infections (topical application, with bacitracin)
Term
Tyrocidins
Definition
interfere with cell membrane function
skin infections caused by Gram-positive cocci (topical application)
Term
Name the 4 antimicrobial agents that act as antimetabolites.
Definition
sulfonamides
isoniazid
ethambutol
nitrofurantoin
Term
sulfonamides
Definition
act as antimetabolites
used to treat some kinds of meningitis and to suppress intestinal flora before colon surgery
Term
Isoniazid
Definition
act as antimetabolites
used to treat tuberculosis (used w/ethambutol)
Term
Ethambutol
Definition
act as antimetabolites
used to treat tuberculosis (used with isoniazid)
Term
Nitrofurantoin
Definition
act as antimetabolites
used to treat urinary tract infections
Term
Name the 5 antimicrobial agents that inhibit protein synthesis.
Definition
Streptomycin
Gentamicin/other aminoglycosides
Tetracyclines
Chloramphenical
Erythromycin
Term
Streptomycin
Definition
inhibit protein synthesis
used to treat tuberculosis (used with isoniazid and rifampin)
Term
Gentamicin/other aminoglycosides
Definition
inhibit protein synthesis
used to treat antibiotic-resistant and hospital acquired infections
Term
Tetracyclines
Definition
inhibit protein synthesis
largest spectrum of activity
used to treat a broad spectrum of bacterial infections and some fungal infections
Term
Chloramphenicol
Definition
inhibit protein synthesis
last drug choice due to bone marrow damage
used to treat broad spectrum of bacterial infections, brain abscesses, and penicillin-resistant infections.
Term
Erythromycin
Definition
inhibits protein synthesis
used to treat gram-positive bacterial infections, some penicillin-resistant infections, and Legionnaires' diease
Term
Name the 2 antimicrobial agents that inhibit nucleic acid synthesis.
Definition
Rifampin
Quinolones
Term
Rifampin
Definition
inhibits nucleic acid synthesis
used to treat tuberculosis and to eliminate meningococci from the nasopharynx
Term
Quinolones
Definition
inhibits nucleic acid synthesis
used to treat urinary tract infections, traveller's diarrhea, effective against many drug-resistant organisms
Term
Name both a broad spectrum agent and a narrow spectrum agent that affects Bacteroides and other anaerobes.
Definition
Broad-Cephalosporins
Narrow-Lincomycin, Clindomycin
Term
Name both a broad spectrum agent and a narrow spectrum agent that affects yeasts.
Definition
broad-Chloramphenicol
narrow-nystatin
Term
Name both a broad spectrum agent and a narrow spectrum agent that affects gram-positive bacteria.
Definition
broad-Gentamicin, Ampicillin
narrow-Penicillin G, Erythromycin
Term
Name both a broad spectrum agent and a narrow spectrum agent that affects gram-negative bacteria.
Definition
broad-Kanamycin
narrow-Polymyxins
Term
Name both a broad spectrum agent and a narrow spectrum agent that affect Streptococci and some gram-negative bacteria.
Definition
broad-Tetracyclines
narrow-Streptomycin
Term
Name both a broad spectrum agent and a narrow spectrum agent that affect Staphylococci and some clostridia.
Definition
broad-Tetracyclines
narrow-Vancomycin
Term
How do certain antimicrobial agents inhibit cell wall synthesis?
Definition
antibiotics such as penicillin and cephalosporin contain beta-lactum ring which attaches to enzymes that cross link peptidoglycan
Term
How do some antimicrobial agents disrupt the cell membrane's function?
Definition
certain polypeptide antibiotics, such as polymyxins, act as detergents and destroy bacterial cell membranes by binding to phospholipids in the membrane, not affective on eukaryotes
polyenes, such as amphoteric B, bind to particular sterols in fungal and animal cell membranes, not affective on bacteria
Term
How do certain antimicrobial agents inhibit protein synthesis in bacteria?
Definition
the agents attack bacterial ribosomes, which differ from animals ribosomes (70S vs. 80S)
Aminoglycosides (such as Streptomycin, neomycin, gentimycin, kantimycin) interfere with translation on the 30S portion of the ribosome
Chlorophenicol binds to 50S subunit, prevents peptide formation
Erythromycin prevents translocation during translation
Term
How do certain antimicrobial agents inhibit the synthesis of nucleic acids?
Definition
Rifamycins bind to the bacterial RNA polymerase and inhibit RNA synthesis (transcription)
Quinolones interfere with DNA replication
Term
Name the 3 side affects that can occur from antimicrobial agents.
Definition
toxicity
allergy
disruption of normal microflora
Term
resistance
Definition
microorganism formerly susceptible to the action of an antibiotic is no longer affected by it
Term
nosocomial infections
Definition
hospital acquired infections
Term
biofilm
Definition
bacteria that congregate and share DNA
Term
What are some nongenetic ways that bacteria acquire resistance?
Definition
1) evasion-bacteria is sequestered in areas that are unreachable by antibiotics, progeny are still susceptible to agent
2)L-forms-bacteria temporarily lose their cell walls and are resistant to antibiotics acting on cell walls, can revert back to forming walls
Term
What are some genetic ways that microorganisms can become resistant to antibiotics?
Definition
1) chromosomal resistance due to random mutations in DNA-not induced by antibiotics but create a favorable environment for resistant mutants
2)extrachromosomal resistance due to genetic transfer-usually due to R plasmids, transfers often occur by transduction and sometimes by conjugation
Resistance can also be transfered horizontally with the help of integrons
Term
Name the 5 Mechanisms of Resistance
Definition
1)alteration of targets
2)alteration of membrane permeability
3)development of enzymes
4)alteration of an enzyme
5)alteration of a metabolic pathway
Term
Explain alteration of targets for resistance
Definition
usually affects bacterial ribosomes, alters DNA so target of antibiotic is modified and antibiotic can no longer bind to target
Term
Explain alteration of membrane permeability for resistance
Definition
genetic changes change the nature of the proteins in the membrane, antimicrobial agent can no longer cross membrane
Term
Explain development of enzymes for resistance.
Definition
Enzymes are developed by bacteria which can destroy or inactivate microbial agents, beta-lactamase breaks beta-lactam ring in penicillin
Term
Explain alteration of an enzyme for resistance
Definition
allows formerly inhibited rxn to occur, sulfonamide-resistant bacteria develop enzyme w/high affinity for PABA and low affinity for sulfonamide, even in presence of sulfonamide bacteria still function
Term
cross-resistance
Definition
resistance to 2 or more similar antimicrobial agents via a common mechanism
Term
What are 3 ways to limit drug resistance?
Definition
1) high levels of antibiotics for long enough to kill all pathogens including mutants or inhibiting them so body defenses can kill them
2) administering 2 antibiotics together to exert additive effect
3) restrict antibiotics to essential uses only
Term
synergism
Definition
inhibitory effect produced by 2 antibiotics working together that is greater than either can achieve alone
Term
antagonism
Definition
decreased effect when 2 antibiotics are administered together
Term
disk diffusion method
Definition
method to determent microbial sensitivity to antimicrobial agents in which antibiotic disks are placed on an inoculated Petri dish, incubated, and observed for zones of inhibition
does not ensure that the antimicrobial agent is bactericidal
Term
E (epsilometer) test
Definition
newer version of diffusion test, uses plastic strip containing gradient of concentration of antibiotic to determine antibiotic sensitivity
Term
dilution method
Definition
two different tests can be done to determine MIC & MBC
organisms are inoculated in a series of tubes containing know quantities of chemotherapeutic agent
Term
MIC
Definition
minimum inhibitory concentration
lowest concentration of an antimicrobial agent that prevents growth in the dilution method
Term
MBC
Definition
minimum bactericidal concentration
lowest concentration of an antimicrobial agent that kills microorganisms, as indicated by absence of growth following subculturing in the dilution method
Term
serum killing power
Definition
determines effectiveness of an antimicrobial agent in which a bacterial suspension is added to the serum of a patient who is receiving an antibiotic and incubated
Term
serum
Definition
liquid part of blood after cells and clotting factors have been removed
Term
automated methods
Definition
identifies the pathogen to the species level and identifies what drug is effective to combat the pathogen
more efficient and less expensive than other methods
Term
What are the 8 attributes of an ideal antimicrobial agent?
Definition
1) solubility in body fluids
2) selective toxicity
3) toxicity is not easily altered
4) nonallergenic
5) maintenance of constant, therapeutic concentration in blood/tissues
6) resistance by microorganisms not easily acquired
7) long shelf-life
8) reasonable cost
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