Term
| where do antibiotics come from? |
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Definition
| they are naturally produced by bacteria and fungi, some are modified or entirely synthetic |
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Term
| what does it mean that antibiotics are selectively toxic? |
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Definition
| that they kill/injure invading organisms w/o harming cells of the host. however, to varying degrees, some antibiotics are toxic or have side effects |
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Term
| what does it mean to say that an antibiotic is bacteriostatic? |
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Definition
| it reversible inhibits metabolic processes of bacteria, (stops growth) |
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Term
| what does it mean to say that an antibiotic is bactericidal? can bacteriostatic antibiotics be bactericidal at higher doses? |
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Definition
| this kind of antibiotic kills susceptible bacteria. some bacteriostatic antibiotics can be bactericidal at higher doses. |
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Term
| what does it mean to say that a drug has a narrow spectrum of activity? extended? broad? |
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Definition
| narrow spectrum antibiotics will only act on a single or limited group of microbes. extended spectrum antibiotics can be modified to be effective against gram + and gram – organisms. broad spectrum antibiotics are active against a wide range of bacteria |
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Term
| what is the difference between antibiotic susceptible and resistant bacteria? |
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Definition
susceptible: in vitro and in vivo susceptibility means the growth can be inhibited or killed by antibiotic.
resistant: in presence of antibiotic the organism will continue to grow and live |
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Term
| can some antibiotics be static for some organisms and cidal for others? what would be a reason for using specifically bacteriocidal drugs? |
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Definition
| some organisms that remain alive at all in the presence of a drug can still make toxin, so bacteriocidals might be needed. also some bacteriocidal drugs like PCN can kill but not at once, while erythromycin stops toxin productin immediately. |
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Term
| what do the best antibiotics target? |
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Definition
| the best antibiotics target biosynthetic processes that are only in bacteria, and not in eukaryotic cells. |
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Term
| what is the first line of antibiotics to be considered? |
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Definition
| antibiotics that inhibit cell wall synthesis, b/c peptidoglycan can't be found in eukaryotic cells. |
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Term
| what are PCN binding proteins, PBPs? |
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Definition
| PBPs bind transpeptidases that are involved in peptidoglycan cross-linking |
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Term
| what are beta lactams? what is their degree of toxicity? |
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Definition
| antibiotics with a beta lactam ring which bind to PBPs which are transpepsidases. PCN, cephalosporin are examples. they have low toxicity. |
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Term
| how do beta lactams work? |
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Definition
| beta lactams bind transpeptidases (PBPs) preventing peptidoglycan cross-linking while the organism is growing and cross-linking can no longer occur, causing lysis of the organism. the organism has to be growing however for the drug to work. |
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Term
| what is a method of resistance, (MOR) that bacteria can use against beta lactams? |
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Definition
| beta lactamases cleave the beta lactam ring, which inactivates antibiotic |
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Term
| what is a MOR gram - bacteria can use to keep antibiotics out? |
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Definition
| spontaneous mutations of porins where antibiotics cannot enter organism |
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Term
| what is a MOR MRSA uses to fight PCN? |
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Definition
| alteration of PBPs that keeps PCN from binding |
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Term
| how does vancomycin work? what is a MOR against it? |
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Definition
| vancomycin interacts with D-ala, D-ala termini preventing cross-linkage of peptidoglycan layers. some organisms change to D-ala, D-lac - which vancomycin doesn't bind to |
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Term
| how does bacitracin work? |
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Definition
| bacitracin prevents movement of peptidogylcan precursors through the cytoplasmic membrane to the cell wall |
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Term
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Definition
| polymyxin inserts itself into gram - outer membranes by interacting with LPS and phospholipids, and interrups the membrane |
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Term
| what are the cell wall antibiotics? |
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Definition
| beta lactams, (PCN, cephalosporin, bind PBPs while organism is growing. vancomycin binds D-ala, D-ala, preventing cross-linkage of peptidoglycan layers. bacitracin, which prevents movement of peptidoglycan precursors through the cytosol. polymyxin which inserts itself into the outer membrane of gram - bacteria. |
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Term
| what do antibiotics that inhibit protein synthesis target? are there selective toxicity concerns for these? |
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Definition
| these disrupt the ribosomes. prokaryotes have 70s, (total), ribosomes while eukaryotes have 80s,(total), these are techinically different, but some similarities, so there is some effect on eukaryotic cell function, (tetracycline can affect teeth development and cause toxicity to renal tubules and inner ear) |
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Term
| what do aminoglycosides do? do they have to do anything first in orde to accomplish this? |
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Definition
| aminoglycosides bind to the 30s ribosome and cause premature release of the peptide chains. however to do this they must penetrate the gram - cell wall and associated with the active transport system, (oxidative) |
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Term
| what are MORs developed against aminoglycosides? |
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Definition
| obligate anaerobes have inactive transport. altered uptake of the drug. modification by addition of adenyl, acetyl or phosphoryl group, (plasmid, transposon encoded), mutation in ribosome -> no binding |
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Term
| how do tetracyclines work? |
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Definition
| these bind to the aminoacyl-tRNA site on the 30s ribosomal subunit and block its attachment to the acceptor site on mRNA ribosome complex, preventing protein synthesis. |
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Term
| what are some MORs against tetracycline? |
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Definition
| decreased uptake or active efflux of the drug from the bacteria mediated by a transporter it can aquire a gene for. (keeps antibiotic conc low inside cell) |
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Term
| what do macrolides do? what is an example of one? |
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Definition
| macrolides prevent polypeptide elongation at the 50S ribosome. |
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Term
| what are some MOR developed against macrolides? |
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Definition
| decreased cell uptake, enzymatic inactivation, and mutation causing decreased binding to ribosome |
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Term
| what are antibiotics that work to inhibit protein synthesis? |
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Definition
| aminoglycosides, (bind 30s, produce premature release of mRNA), tetracycline, (bind 30s, blocks aminoacyl-tRNA attachment to acceptor site on mRNA ribosome complex) macrolides, (prevent polypeptide elongation by binding to 50s subunit) |
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Term
| what are DNA gyrases? do eukaryotes have these? |
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Definition
| a topoisomerase that keeps cells from twisting around itself. eukaryotes do not have these. |
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Term
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Definition
| block activity of DNA gyrase, prevent DNA from being replicated b/c it keeps getting twisted. |
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Term
| what is an MOR for quinolone? |
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Definition
| mutations in DNA gyrase so that it can no longer bind |
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Term
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Definition
| this inhibits DNA dependent RNA polymerase which inhibits initiation of transcription, by binding to the beta subunit |
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Term
| is RNA polymerase in prokaryotes different than that in eukaryotes? |
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Definition
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Term
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Definition
| mutation in RNA polymerase that frequently happens when the anitbiotic is used alone |
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Term
| what are antibiotics that inhibit nucleic acid synthesis? |
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Definition
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Term
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Definition
| inhibit dihydropteroate synthase which inhibits folic acid synthesis in prokaryotes. |
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Term
| what does trimethoprin do? |
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Definition
| inhibits dihydrofolate reductase, (bacteria need to make their own folic acid, they cannot use the folic acid humans make) |
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Term
| what antibiotics inhibit the metabolism? |
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Definition
| sulfonamides and trimethoprin |
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Term
| what some considerations in terms of selecing antimicrobial therapy? |
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Definition
| ID organism and susceptibility patterns, site of infection, pt factors, (age, liver/kidney disfunction, pregnant, immune status), pharmacologic factors, (delivery, distrobution, elimination, toxicity, interactions with other drugs) |
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Term
| what are the two ways of approaching antibiotic prescription? |
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Definition
| empirical theory or selection of therapy with known etiology |
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Term
| what is empirical theory? |
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Definition
| presumtive prescription of antibiotics, assuming you know the organism, susceptibility pattern, etc. justification is improvement of morbidity, mortality, or public health. (writing a rx for a pt you think has chlamydia/gonhorra, or for a pt you think has spinal menigitis) |
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Term
| what are considerations for empirical theory? |
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Definition
| knowledge of association between pathogen and disease: (streptococcus pneumonia = number 1 cause of pneumonia and meningitis, so you know what rx to write. pt hx: including age, immune status, disease state, pregnancy?, travel? broader spectrum of therapy: may be required to cover possible organisms that may be causing the infection |
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Term
| what is selection of therapy with known etiology? what should be considered in terms of what organism it is, what it will respond to, continuing conditions, and local environment? |
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Definition
| when you need to know what the organism is, ex if the bacteria has a hx of resistance to antibiotics, you may want a narrower, more efficient spectrum antibiotic. a cx can give definite ID of organism within 24 hrs, which helps with initial therapy and antibiotic susceptibility tests can be done within 48 hrs as well. microbiological assessment can be continued for duration of tx, our own normal flora may carry antibiotic resistance genes that can be passed on to the pathogen. local epidemiology on certain species' incidence is also helpful |
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Term
| what is an minimal INHIBITORY concentration, (MIC)? how is it done? how is the minimal bacteriCIDAL concentration done? |
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Definition
the organism is grown in broth culture, and serial dilutions of an antibiotic are added to different test tubes. the tube where the least antibiotic and still lack of bacterial growth exist is the minimal inhibitory concentration. minimal bactericidal concentration testing will be done on a plate,
when organism doesn’t grow even in removal of antibiotic, this is the minimal bacteriCIDAL concentration. |
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Term
| what is the agar disk diffusion method? how is it done? what does it tell you? |
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Definition
| bacteria are plated and little discs of differing antibiotic conc. are placed on it. it is incubated overnight and zones of inhibition are looked for and measured. this will tell you if the organism is sensitive or resistant to the antibiotic, in a QUALITATIVE "antibiogram" |
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Term
| what is the gradient elution test? what information does it provide? |
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Definition
| tries to make the agar disk diffusion method a little more quantitative, (mix between broth culture and agar disk test). |
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Term
| what are pharmacodynamic considerations? for bacteriostatic, bacteriocidal drugs? |
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Definition
| consideration of the relationship between antibiotic conc. and antimicrobial effect. (in vitro vs what is reasonable in vivo). bacteriostatic agents arrest the growth or replication of bacteria at serum levels achievable in the pt. bacteriocidal agents kill bacterial at serum levels achievable in the pt, should be used when defenses are impaired. |
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Term
| what are the two kinds of bacteriocidal agents? |
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Definition
| those that effect conc. dependent killing and those that effect time dependent killing. |
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Term
| how does the action of drugs that enact concentration dependent killing look? |
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Definition
| the rate and extent increases with increasing concentration, (single dose antibiotics) |
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Term
| how does the action of drugs that enact time dependent killing look? |
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Definition
| activity continues as long as serum concentrations are at a certain level. |
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Term
| what is the post antibiotic effect, (PAE)? what are considerations for drugs that lack this? |
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Definition
| some antibiotics bind to a target in the organism and even after the conc of the antibiotic gets to be low, they remain stuck to the target and it still has its effect. drugs without a PAE should remain above the MIC serum concentration for intervals between dosing. this plays a part in the efficacy of some one-daily dose regimes |
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Term
| what are pharmacokinetic considerations? how does this affect route of administration? |
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Definition
| absorption, distrobution, and elimination of the drug from the body. this includes oral administration and parenteral (IV) administration. |
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Term
| why might oral routes of administration be chosen? |
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Definition
| less costly and few complications? |
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Term
| why might paraenteral, (IV) administration be considered? |
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Definition
| if the drug is poorly adsorbed from the intestinal tract, if the pt has disease that would impair absorption, or if the pt is critically ill/suffers from menigitis,(to get through the blood brain barrier) or endocarditis |
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Term
| what are some conditions that can alter antimicrobial kinetics? (dosage vs state of vascular availability) |
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Definition
| impaired renal/hepatic function leads to reduced elimination, and dosage needs to be decreased. pts with burns, CF, or trauma, dosage should be increased. dosage should also be altered in elderly, neonates, and in pregnancy. |
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Term
| when might conc. of bodily fluids need to be taken into account? what organs or areas of the body have special consideration for this? |
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Definition
| CSF concentration is limited due to blood/brain barrier. the prostate and eye have limited distrobution as well. |
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Term
| what are some considerations in terms of antimicrobial safety? in terms of pt hx? |
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Definition
| some anti-microbials are toxic to eukaryotic cells and are thus reserved for life-threatening conditions. an allergy, drug and medical hx should be obtained. groups with frequent adverse rxns include: neonates, elderly, renal failure, and AIDs pts |
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Term
| what are some advantages in terms of combining antimicrobial drugs, synergism? |
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Definition
| this makes the antibiotic more broad spectrum, can treat polymicrobial infections more effectively, decrease the emergence of antibiotic resistance, (harder to generate resistance against 2 drugs), and reduce dose-related toxicity, (smaller dose of 2 drugs w/different side effects) |
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Term
| to obtain rationale for synergistic antibiotic rx, what increase in inhibition or killing should be seen in MIC or MBC vs used alone? |
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Definition
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Term
| what is an example of synergism leading to enhancement of antimicrobial uptake? |
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Definition
| aminoglycosides can have a difficult time getting into a cell, but given with penicillin to break up the cell wall, aminoglycosides can enter |
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Term
| what are other mechanisms of synergism in terms of metabolic sequences or enzyme inhibition? |
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Definition
| blockade of sequential steps in a metabolic sequence or inhibition of enzymatic inactivation, (ex. inhibition of B-lactamase by B lactamase inhibitor drugs) |
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Term
| what is an example of antagonism between antibiotics if taken at the same time? |
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Definition
| inhibition of cidal activity by static agents, (cidals can require growth to function) |
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Term
| can one antibiotic enzymatically inactivate another? |
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Definition
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Term
| what things must an antibiotic do to be effective? |
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Definition
| it must associate with the bacteria and penetrate the envelope. it must be transported to an intracellular site of action. it must bind to its target |
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Term
| what are mechanisms of antibiotic resistance? |
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Definition
| prevention of access to the target, alteration of the target or aquisition of the ability to destroy or modify the antibiotic |
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Term
| how can various bacteria prevent access of antibiotics to their targets? how is the action of PCN and ceph affected? aminoglycosides? vancomycin? can mutations in porins prevent entrance of more than one antibiotic into the cell, (cross resistance)? |
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Definition
| PCN and cephalosporin can be blocked by mutations in the outer membrane where porins, (OMP f), shrink and the drugs can't get in. outer membrane protein expression can be decreased for aminoglycosides so they can't enter either. porins on gram - bacteria are normally too small for vancomycin even without development of resistance. and cross resistance does happen. |
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Term
| what is another way that antibiotic access to the target can be prevented? |
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Definition
| active efflux of the antibiotic, bacteria can aquire the "tet" gene which expresses a transporter that flushes tetracycline out of the cell |
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Term
| what are examples of antibiotic targets in bacteria being altered for PCN, aminoglycosides, and vancomycin? |
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Definition
| with PCN, transpeptidase, (PBP), can be altered. with vancomycin, the termini can be altered. with aminoglycosides, the 30s subunit can be altered |
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Term
| how did staphylococcus aureus become methicillin resistant, (MRSA)? |
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Definition
| staphylococcus aureus produce PBP2a', which has a low affinity for beta-lactam antibiotics, which allowed cell wall synthesis to continue in their presence. They also produced betalactamases which reduced the efficacy of PCN/cephalosporin. Methicillin was then developed b/c it couldn't be affected by betalactamase. staphylococcus aureus then developed another transpepdidase that did not bind to methicillin. staphylococcus aureus then became methicillin resistant, (MRSA) |
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Term
| what is PBP2a'? what encodes it? how is it tested for? |
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Definition
| PBP2a' is the altered transpeptidase which as a low affinity for beta-lactam antibiotics. it is encoded by the mecA gene. it is tested for using PCR and antibody test for PBP2a. the organism can express this gene at really low level, so you can look for this gene using PCR instead of looking directly at resistance. |
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Term
| what strains of bacteria can develop vancomycin resistance? |
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Definition
| strains with VanA,B and D genes can replace the last ala with lac so vancomycin can't bind. |
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Term
| what is used as the last resort for MRSA and enterococci? |
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Definition
| vancomycin, but VRE have emerged since the late 1980s |
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Term
| what are some examples of enzymes that cleave antibiotics in defense of the bacteria? are there ones for specific antibiotics? what is ESBL? |
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Definition
| beta lactamases. penicillinase only affects PCN, cephalosporinase only effects cephalosporins. ESBL are extended spectrum beta lactamases these can affect PCN and cephalosporin for ex. |
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Term
| how are antibiotics like aminoglycasides be modified by bacterial enzymes? |
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Definition
| aminoglycasides be modified via N-acetylation, phosphorylation, and 0-adenylation |
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Term
| what are some reasons for phenotypic resistance, (therapeutic resistance despite susceptibility in vitro), in terms of beta-lactams? abcesses? intracellular growth? |
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Definition
| bacteria may not be dividing and beta-lactams cannot work b/c they require growth. bacteria could be walled off inside an abcess and then antibiotic can't get to it. the organism could also be growing intracellularly, and again, out of antibiotic range. |
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Term
| what is an example of genetically originated resistance in chromosomes? plasmids? transposons? |
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Definition
| chromosomal point mutations, low frequency, usually resistance to a single antibiotic. plasmids, frequently mediate resistance to multiple antibiotics (through R factors), most common in gram -. transposons have potential for widespread dissemination of resistance genes, (through R-determinants), can't replicate independent of a plasmid/chromosome, but translocates within a chromosome, plasmid, or phage DNA. |
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Term
| what is the epidemiology of resistance? |
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Definition
| clinical use of antibiotics is followed by resistance, increase use -> increase resistance. preexisting resistance strains can be selected for by antibiotic usage |
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