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coined the term chemotherapy, also discovered salvarsan in 1910 to treat syphilis |
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discovered a red dye (prontosil) in 1935 that inhibits growth of gram + organisms |
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found that antimicrobial activity of prontosil was due to sulfanilamide portion of molecule discoveries stimulated development of sulfa drugs |
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discovered that Penicillin inhibits growth of microorganisms |
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isolated penicillin and developed methods of mass production |
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discoverer of streptomycin in the 1940s |
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use of chemical substances to kill pathogenic organisms without injuring the host |
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any chemical substance used in medical practice |
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special group of chemotherapeutic agents used to treat diseases caused by microbes |
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What does antibiotics literally mean? |
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chemical substance produced by microorganisms which has the capacity to inhibit growth and even destroy bacteria and other microbes in dilute solution |
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agents synthesized in the lab |
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antimicrobial agents made partly by lab synthesis and partly by microorganisms |
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What organism caused the Bubonic Plague/Black Death? |
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Yersinia pestis transmitted by rat bites, fleas, etc. |
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must harm the microbes without causing significant damage to the host |
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a drug causes harm to the host |
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a drug successfully eliminates the pathogenic organism if the level is maintained over a period of time |
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maximum tolerable dose per kg of body weight divided by minimum dose per kg of body weight |
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range of different microbes against which an antimicrobial agent acts can be broad or narrow |
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5 Drug mechanisms of action |
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inhibition of cell wall synthesis disruption of cell membrane function inhibition of protein synthesis inhibition of nucleic acid synthesis action as antimetabolites |
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a substance, similar in structure to normal metabolites, that prevents a cell from carrying out an important metabolic reaction |
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What are the 2 ways that antimetabolites work? |
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by competitively inhibiting enzymes by being erroneously incorporated into important molecules such as nucleic acids |
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What is an example of an antimetabolite that competitively inhibits enzymes? |
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sulfanilamide, similar to PABA, competitively inhibits enzyme that acts on PABA, so no folic acid can be made |
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What are 2 examples of metabolites that erroneously incorporate into nucleic acids as analog purines & pyrimidines? |
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purine analog vidarabine & pyrimidine analog idoxuridine |
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Name the 4 antimicrobial agents that inhibit cell wall synthesis. |
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Penicillin Cephalosporins Carbapenems Bacitracin |
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inhibits cell wall synthesis used to treat wide variety of infections, mostly gram-positive organisms |
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inhibit cell wall synthesis used to treat a wide variety of infections when allergy or toxicity makes other agents unsuitable |
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inhibit cell wall synthesis used to treat mixed infections, nosocomial infections, and infections of unknown etiology |
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inhibits cell wall synthesis used to treat skin infections (topical application) |
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Name the 2 antimicrobial agents that interfere with cell membrane function. |
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interfere with cell membrane function used to treat skin infections (topical application, with bacitracin) |
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interfere with cell membrane function skin infections caused by Gram-positive cocci (topical application) |
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Name the 4 antimicrobial agents that act as antimetabolites. |
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sulfonamides isoniazid ethambutol nitrofurantoin |
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act as antimetabolites used to treat some kinds of meningitis and to suppress intestinal flora before colon surgery |
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act as antimetabolites used to treat tuberculosis (used w/ethambutol) |
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act as antimetabolites used to treat tuberculosis (used with isoniazid) |
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act as antimetabolites used to treat urinary tract infections |
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Name the 5 antimicrobial agents that inhibit protein synthesis. |
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Streptomycin Gentamicin/other aminoglycosides Tetracyclines Chloramphenical Erythromycin |
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inhibit protein synthesis used to treat tuberculosis (used with isoniazid and rifampin) |
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Gentamicin/other aminoglycosides |
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inhibit protein synthesis used to treat antibiotic-resistant and hospital acquired infections |
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inhibit protein synthesis largest spectrum of activity used to treat a broad spectrum of bacterial infections and some fungal infections |
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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. |
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inhibits protein synthesis used to treat gram-positive bacterial infections, some penicillin-resistant infections, and Legionnaires' diease |
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Name the 2 antimicrobial agents that inhibit nucleic acid synthesis. |
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inhibits nucleic acid synthesis used to treat tuberculosis and to eliminate meningococci from the nasopharynx |
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inhibits nucleic acid synthesis used to treat urinary tract infections, traveller's diarrhea, effective against many drug-resistant organisms |
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Name both a broad spectrum agent and a narrow spectrum agent that affects Bacteroides and other anaerobes. |
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Broad-Cephalosporins Narrow-Lincomycin, Clindomycin |
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Name both a broad spectrum agent and a narrow spectrum agent that affects yeasts. |
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broad-Chloramphenicol narrow-nystatin |
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Name both a broad spectrum agent and a narrow spectrum agent that affects gram-positive bacteria. |
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broad-Gentamicin, Ampicillin narrow-Penicillin G, Erythromycin |
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Name both a broad spectrum agent and a narrow spectrum agent that affects gram-negative bacteria. |
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broad-Kanamycin narrow-Polymyxins |
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Name both a broad spectrum agent and a narrow spectrum agent that affect Streptococci and some gram-negative bacteria. |
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Definition
broad-Tetracyclines narrow-Streptomycin |
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Name both a broad spectrum agent and a narrow spectrum agent that affect Staphylococci and some clostridia. |
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Definition
broad-Tetracyclines narrow-Vancomycin |
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How do certain antimicrobial agents inhibit cell wall synthesis? |
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antibiotics such as penicillin and cephalosporin contain beta-lactum ring which attaches to enzymes that cross link peptidoglycan |
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How do some antimicrobial agents disrupt the cell membrane's function? |
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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 |
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How do certain antimicrobial agents inhibit protein synthesis in bacteria? |
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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 |
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How do certain antimicrobial agents inhibit the synthesis of nucleic acids? |
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Rifamycins bind to the bacterial RNA polymerase and inhibit RNA synthesis (transcription) Quinolones interfere with DNA replication |
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Name the 3 side affects that can occur from antimicrobial agents. |
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toxicity allergy disruption of normal microflora |
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microorganism formerly susceptible to the action of an antibiotic is no longer affected by it |
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hospital acquired infections |
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bacteria that congregate and share DNA |
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What are some nongenetic ways that bacteria acquire resistance? |
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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 |
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What are some genetic ways that microorganisms can become resistant to antibiotics? |
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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 |
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Name the 5 Mechanisms of Resistance |
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1)alteration of targets 2)alteration of membrane permeability 3)development of enzymes 4)alteration of an enzyme 5)alteration of a metabolic pathway |
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Explain alteration of targets for resistance |
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usually affects bacterial ribosomes, alters DNA so target of antibiotic is modified and antibiotic can no longer bind to target |
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Explain alteration of membrane permeability for resistance |
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genetic changes change the nature of the proteins in the membrane, antimicrobial agent can no longer cross membrane |
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Explain development of enzymes for resistance. |
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Enzymes are developed by bacteria which can destroy or inactivate microbial agents, beta-lactamase breaks beta-lactam ring in penicillin |
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Explain alteration of an enzyme for resistance |
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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 |
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resistance to 2 or more similar antimicrobial agents via a common mechanism |
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What are 3 ways to limit drug resistance? |
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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 |
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inhibitory effect produced by 2 antibiotics working together that is greater than either can achieve alone |
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decreased effect when 2 antibiotics are administered together |
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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 |
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newer version of diffusion test, uses plastic strip containing gradient of concentration of antibiotic to determine antibiotic sensitivity |
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two different tests can be done to determine MIC & MBC organisms are inoculated in a series of tubes containing know quantities of chemotherapeutic agent |
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minimum inhibitory concentration lowest concentration of an antimicrobial agent that prevents growth in the dilution method |
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minimum bactericidal concentration lowest concentration of an antimicrobial agent that kills microorganisms, as indicated by absence of growth following subculturing in the dilution method |
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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 |
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liquid part of blood after cells and clotting factors have been removed |
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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 |
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What are the 8 attributes of an ideal antimicrobial agent? |
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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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