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126 Cards in this Set

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  • Back
antibiotics that affect membrane permeability
the POLYMYXINS: polymyxin B
-cidal agents (cell growth NOT required)
-selective against G(-) enteric rods (esp. Pseudomonas)
mechanism of bacteriocidal action of Polymyxin antibiotics
-positively charged polypeptide antibiotic binds first to the negatively charged LPS in outer membrane, then to cytoplasmic membrane phospholipids, causing membrane leakage
how are polymyxins commonly used?
-commonly used as topical agents- systemic use largely supplanted by more effecitve and less toxic agents
what are polymyxins selective against?
-selective against G(-) enteric rods (esp. Pseudomonas)
Antibiotics that work as inhibitors of protein synthesis:
-inhibitors of 30S ribosome {Aminoglycosides (e.g. Streptomycin, Gentamycin)}
-inhibitors of RNA-30S ribosome binding {Tetracyclines: tetrocycline and doxycycline}
-Inhibitors of 50S ribosome {eg Erythromycin, Azithromyci}
-blocks chain elongation {Chloramphenicol}
-inhibits peptidyl transfer {Clindamycin}
-Inhibition of translation by other mechanisms: MUPIROCIN
problems with streptomycin
-positively charged at physio pH
-does not penetrate bacteria readily, and some metabolic activity by the bacterium is needed for streptomycin to enter
-actin is INHIBITED under anaerobic conditions or acid conditions-- as in urine
the 1944 discovery of streptomycin (an aminoglycoside) was important because it extended range of antibiotic to what kind of organisms?
Mycobacterium tuberculosis and to many gram-negative organisms
-cidal mechanism of aminoglycosides
-streptomycin enters cell through membrane imperfections
-binds subunit of 30S ribosome protein, distorting acceptor site-- causing misreading
-misreading causes "bad" proteins to be made, membrane leakiness ensues, streptomycin uptake increases
-at higher [streptomycin] inhibits formation of initiation complex and of peptide bond formation
explain how streptomycin resistant mutants are readily selected for:
streptomycin "selects" for these mutants by providing an enviro that favors their growth inside, while inhibiting non-resistant bacteria
how does GENTAMYCIN differ from STREPTOMYCIN
both in hibit 30S ribosomal protein, but GENTAMYCIN interacts with more than one ribosomal protein on the 30S subunit

hence one cannot obtain resistance to these agents in one step as with streptomycin
why is use of aminoglycosides limited to serious infections?
toxic effects, damaging CN VIII (vestibulocochlear) or renal function
what type of antibiotics are preferable in those with compromised immune systems? -static or -cidal
BACTERIOCIDAL antibiotics are often perferred in such patients

why aminoglycosides are often used w/ them
broad spectrum antibiotic (including mycoplasma, rickettsia and chlamydia)
well absorbed orally
bacteriostatic effect of tetracycline
blocks binding of aminoacyl-RNA to 30S ribosomal subunit
most potent tetracylcine derivative
TIGECYCLINE (chemical side chain, makes it REFRACTORY to common mechanism of tetracycline RESISTANCE that INVOLVES an EFFLUX PUMP) introduced by Wyeth 2005
antibiotic that may mottle enamel in children's teeth
and are
not to be used in pregancy bc of potential tetrogeneity
antibiotic action of ERYTHROMYCIN
bacteriostatic inhibitor of 50S ribosomal function, blocks chain elongation

widely used drug
spectrum of activity similar to penicillin G (but includes mycoplasma and chlamydia)
spectrum of Erythromycin activity
spectrum of activity similar to penicillin G (but includes mycoplasma and chlamydia)
an ANTIBIOTIC related to ERYTHROMYCIN, but with higher activity and slightly broader spectrum
how does AZITHROMYCIN give high tissue concentrations?
oral drug that gives high and sustained tissue concentrations, which increase at a site of infection (attributable to uptake by phagocytes which migrate to the site)
antibiotic action of chloramphenicol
-bacterioSTATIC (but in some species leads to -cidal effect)
-blocks polypeptide chain elongation
why is CHLORAMPHENICOL NOT widely used?
rarely induces uncommon, but sometimes lethal aplastic anemia

-restricted to infection in which it is vital
-useful against some ANaerobes, particularly in bowel (B. fragilis)
**sold OTC in many countries
antibiotic action of CLINDAMYCIN
-inhibits peptidyl transfer
(derivative of linocmycin, has activity against G+ and moderate activity against anaerobes)
antibiotic action of OXAZOLIDINONES
-probably work by inhibiting tRNA translocation
-interacts with 16S RNA and 23S rRNA of the 30S and 50S ribosomal subunits
OXAZOLIDINONES (ZYVOX/linezolid) are highly active against
G+ organisms
potential for treating especially VREF, potentially MRSA, VRSA and other multiply resistant bacteria
relatively new Antibiotic, first used in april 2000, geared toward multiply resistant bacteria
ZYVOX (linezolid)

first clinical isolates of linezolid-resistant VREF were isolated by April 2001
antibiotic action of STREOTPGRAMINS:
-binds to the 50S subunit
potential for treating MRSA, VREF and other multiply resistant bacteria
antibiotic action of MUPIROCIN
-static at low concentrations
-cidal at high concentrations (topical administration, maybe due to disruption of cell wall synthesis)

binds specific tRNA synthetase and prevents its function, resulting in to charged Ile-tRNAs available for protein synthesis

-useful from MRSA, esp against nasal carrier state
-also for topical treatment of impetigo caused by S. aureus or S pyogenes
-weaker effects aginst natural surface flora
-useful from MRSA, esp against nasal carrier state
-also for topical treatment of impetigo caused by S. aureus or S pyogenes
-weaker effects aginst natural surface flora
QUINOLONES (ciprofloxacin and moxifloxacin)
NITROIMIDAZOLES (metronidazole)
the quinolones (CIPROFLAXACIN AND MOXIFLOXACIN) are active against what type of bacteria, what type of infections?
active vs. G(-) enteric bacilli and some G(+) cocci and P. aeruginosa.

used for a variety of infections: notably UTI, respiratory, and even anaerobic

cipro = antibiotic of choice for therapeutic (and even prophylactic) treatment for anthrax (B. anthracis)
antibiotic of choice for therapeutic (and even prophylactic) treatment for anthrax (B. anthracis)
CIPROFLOXACIN (a Quinolone= an inhibitor of DNA replication)
antibiotic action of quinolones (CIPROFLAXACIN and MOXIFLAXACIN)
-inhibits the enzyme DNA gyrase necessary for DNA synthesis
these antibiotics should not be prescribed for pregnant women or children bc they can damage growing bone
quinolone derivatives:
antibiotic action of: Nitroimidazoles (METRONIDAZOLE) {anaerobic drug}
-active form of drug binds DNA and fragments it
-activation requires anaerobic conditions (reduction and activation by an electron transport protein: ferredoxin)
antibiotic useful against anaerobic bacteria, especially Bacteroides species
METRONIDAZOLE (nitroimidazole)
antibiotic inhibitor of RNA synthesis
antibiotic action of Rifampin
-inhibits transcription by binding to the BETA subunit of bacterial RNA polymerase, inhibiting specific binding to DNA
Rifampin is commonly used to treat what?
broad spectrum, often used in combination with other antibiotics since resistance develops rapidly when used alone.
{example: combined with ISONIAZID or PYRAZINAMIDE (major Tx against TB)}
-drug is efficiently secreted in saliva, useful as a prophylactic against infectious bacteria that enter via nasopharyngeal route (e.g. N. menigitidis)
important anti-TB drug (bacteriostatic against tubercle bacilli)
mechanism of action unknown
important anti-TB drug (bacteriocidal) mechanism unknown
-requires activity of mycobacteria amidase to become activated
Pontentially antagonistic antibiotic agents
an agent that requires growth (eg penicillin) + a bacteriostatic agent (eg tetracycline)
Potentially synergistic antibiotics
an agent which damages the cell well/membrane (penicillin/polymyxin) + a cidal agent which is taken up poorly by the bacterium (aminoglycoside)
more than one antibiotic agent should be used ONLY when:
1) synergistic action can be expected
2) susceptibility pattern of the most probable pathogens requires the use of more than one agent
3) the likelihood of development of bacterial resistance is reduced
4) the dosage of a toxic drug can be reduced
5) a polymicrobial infection requires use of more than one agent
disadvantages of combination antibiotic therapy
increased risk of side effects and superinfections;
possible drug antagonism;
increased cost
general reasons for antibiotic inactivity
1) Antibiotic is inactivated, extracellularly, intracellularly, or both
2) Antibiotic cannot enter the cell, or is actively pumped out
3) Bacterial cell contains an altered enzyme that resists action of antibiotic
4) antibiotic can enter the cell, but the drug-binding target site is replaced
enzymatic inactivation of antibiotics
-cleave beta-lactam ring {penicillins, cephalosporins, etc..}
Aminoglycoside modifying enzymes
generally modify aminoglycosides during transport ax cytoplasmic membrane

acetylation, adenylylation and phosphorylation kanamycin, gentamycin, streptomycin
chloramphenicol is inactivated by
chloramphenicol acetyltranferase
Erythromycin is enzymatically inactivated by:
erythromycin ESTERASE- hydrolyzes lactone ring
decreased expression of OUTER MEMBRANE PORINS inhibits what antibiotic actions?
nalidixic acid
altering membrane transporters of inner membrane:
-alters activity of what antibiotic?
-is relatively rare because?
aminoglycosides affected

but rare since usually deleterious regarding PMF
antibiotics inactivated by efflux mechanisms (that actively pump them out of cell)
(methylation of 23S rRNA (comonent of 50S ribosome) is basis for resistance to what antibiotic?

(tet resistance also via methylation of unknown ribosomal target)
(alteration of S12 (comonent of 30S subunit) is basis for resistance to what antibiotic?
most common mechanism for Em^r and Sm^r (erythromycin and streptomycin resistances)
methylation of 23S rRNA (for Em)
alteration of S12 (for Sm)
Alteration of cell wall precursor targets underlies resistance to these antibiotics
mechanism for Vancomycin and Teichoplanin resistance by alteration of cell wall precursor targets
enzyme (related to D-ala-D-ala ligase) makes D-ala-Dala-lactate, which substitutes for D-ala-D-ala in PG precursors and is not recognized by Vm or Tp
alteration of PBP's affinity is associated with resistance to what antibiotics?
Methicillin resistance
pen^r (in Neisseria, H. influenzae, and P aeruginosa)
altered DIHYDROPTEROATE SYNTHETASE (= altered target/ unerlies resistance to what antibiotic)
altered DHFR (alteration of HOST)
or plasmid encoding DHFR (subs pathway)
underlie resistance to what antibiotic?
-axn bind to sterols (esp. ERGOSTEROL) in cell membranes, damaging cell membranes
-specificity ([ergosterol] in fungal >> animal cells)
-toxicity: poorly absorbed from GI tract
prinicipal sterol in fungal membranes
(vs. cholesterol in animal membranes)
toxic drug used topically and for oral fungal infections "swish and swallow"
"swish and swallow" method, works bc poorly absorbed from GI tract

too toxic for other systemic use
anti-fungal action of amphotericin B
fungicidal (destroys membrane integrity)

binds to ergosterol in cell membranes
antifungal action of Nystatin
fungistatic (except at high, nonphysio dosages)
Azoles are drugs for what type of infections?
useful for treatment of oral candidiasis (thrush) and other systemic mycoses; important in patients who may require chronic suppression of recurrent fungal infections (eg FLUCONAZOLE, KETOCONAZOLE)
antifungal action of AZOLES
-inhibition of ergosterol syntehsis, by inhibition of cyt p450 14a-demethylase
-membrane and cell properties are disturbed
-hyphae synthesis is inhibited, making fungi more easily phagocytosed by PMNs and M0s
FLUCANAZOLE (diflucan)
-azole (inhibits cell membrane synthesis)
-systemic antifungal (thrush, etc..)
rare toxicity associated with AZOLE antifungal drugs
hepatotoxicity in 0.01% of patients
Antifungal action of the Echinocandins:
-inhibitors of glucan synthesis
-inhibit the 1,3-beta-D-glucan synthase
-an ECHINOCANDIN (inhibitor of cell wall (glucan) synthesis)
Antifungal drugs (antimetabolites)
Flucytosine: inhibits fungal protein synthesis by replacing uracil with 5-flurouracil in fungal RNA
(also inhibits thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate and thus fungal DNA synthesis)
antifungal action of FLUCYTOSINE
-fungicidal or static, depending on fungal isolate
-inhibits fungal protein synthesis by replacing uracil with 5-flurouracil in fungal RNA
(also inhibits thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate and thus fungal DNA synthesis)
mechanisms of resistance to antifungal compounds
NO aquired resistance mechanisms that inactivate antifungal drugs have thus far been discovered
killing of all microorganisms (bacteria, fungi, viruses)
agent used to kill bacteria (fungi, viruses)
using a germicide on an inanimate object (does not imply killing all organisms, but only those that are pathogens likely to be encountered in that setting, eg: application of lysol (containing phenol) to floors, or of alcohol to thermometers)
application of chemical agents to the surface of the HUMAN BODY to kill or inhibit pathogenic material
presence of pathogenic bacteria in living tissue
tissue without pathogenic bacteria
lowering bacterial content on fomites w/o necessarily killing all bacteria (eg: washing dishes in hot soap and water)
agent used in small (non-toxic) concentrations to inhibit the growth of organisms in food, vaccines, etc..
PC>1: more effective than phenol
PC<1: less effective than phenol
(STAPHENE (disinfectant in lab) PC>10)
Descending order of resistance
of various biological agents
to germicidal chemicals
3 main physical agents of disinfection
HEAT (wet or dry)
what type of heat is most effective in disinfection?
WET HEAT more effective than dry heat
water molecules speed the denaturation of proteins in abcteria by providing H-bonds to replace those normally present in proteins
AUTOCLAVE provides what type of conditions?
for killing of what?
121 degrees C, 15 pounds

will kill ALL BACTERIA (including spores) within 15 minutes
what are the disadvantages of autoclaving?
complicated, unsuitable for heat-sensitive materials (i.e. most plastics)
can spores be killed with dry heat? when should dry heat be used?
-yes, but requires higher temps and longer time (160 C for 1.5-2 hours vs 121 degrees for 15 mins with wet)
-used when materials would be damaged by water: powders, surgical dressings
boiling at atmospheric pressure will kill most....
bacteria (but NOT spores) in 5-10 minutes
Pasteurization (classical treatment)
-what does it involve?
-what does it kill?
-63 degrees C for 30 minutes
-kills common milk-borne pathogens (tubercle bacillus, Salmonella, Streptococcus and Brucella) and reduces total bacterial count to 1-3% of initial level
Pasteurization (HTST)
High Temperature Short Time treatment
yields results similar to what?
conditions: 71-72 degrees C for 15-17 seconds
yields simlar results to classical treatment
test organism historically used to monitor pasteurization
Coxiella burnetii, agent of Q fever
(a rickettsia, good test organism because it is relatively heat resistant)
today milk is deemed pasteurized if it tests negative for what?
alkaline phosphatase
(enzyme that denatures underconditions simlar to those that kill C. burnetti, and its loss of activity is quicker and easier to assay than monitoring the presence of viable C. burnetti)
-Used for heat-sensitive liquids
-Allows retention of high quality, no effects of heat treatment
-Can be performed very quickly for small samples
-Used for vaccines and a number of drug formulations
Filtration Pore Sizes:
to exclude most bacteria?
to exclude ALL bacteria?
0.45 micron- excludes most bacteria
0.22 micron- excludes ALL bacteria
drawbacks of disinfection by FILTRATION
-- Many viruses pass through all common filters
-- Filters tend to clog - sometimes need series progressing from large to small pore size
-- Expense-
most commmon application of RADIATION (in sterilization)
UV light emitted by mercury vapor lamps (non-ionizing)
-used to decrease bacterial content of air in ORs, barracks, nurseries, restaurants, etc..
antibacterial action of UV radiation
UV wavelengths absorbed by nucleic acids and proteins,
-cross-links thymine dimers (interferes with DNA replication, not lethal)
-causes toxic intracellular peroxide formation
advantages/disadvantages of UV radation as disinfectant
simple, can be left on for long time w/o monitoring

-poor capacity to penetrate anything, but air, irritation and damage to human tissue, should not be viewed directly, intensity should be regulated
miscellaneous physical methods of sterilzation
drying (lowers water levels below that needed for bacterial growth)
high osmotic pressure (salt/sugar
ionizing radation as disinfectant
xray, gamma rays, high energy radiation

not widely used
disadvantage: containment, changes tastes?
chemical methods of disinfection target what?
Lipids, proteins and DNA
examples of chemical methods of disinfection
ethylene glycol is used in what kind of sterilization?
alkylating agent, toxic to humans, suitable only for dry materials, used in presence of CO2 (bc of explosivity)
optimal effective concentration of ethyl alcohol
60-70 precent
how does ethanol work as a sterilizing agent?
denatures proteins, not reliable against all organisms, subject to legal restrictions, where as isopropyl alcohol has NO restrictions, is slightly more potent, less volatile, but more $$$
commonly used as sterilizing agent on skin before injections, in tinctures of antisepectics and germicides or in jars where thermometers are stored
does ethanol kill spores?
halogens used as antisepctics
iodine (KI): reliable skin antiseptic; chlorine: widely used as a gas in water supplies and surface cleaner in hypochlorite soln in food industry
cationic detergents are active against bacteria by what axn
disrupting cell membranes and dissolving lipid films that may protect bacteria
why are anionic detergents less effective than cationic detergents
molecules are repelled by the negative charge of the bacterial surface
disadvantages of cationic detergents
not active against Pseudomonas (most common agent in burn infection), poorly active against tubercle bacilli
these agents leave a tenacious bactericidal film on surfaces of treated objects
cationic detergents
what kind of anticeptic agent is Hydrogen peroxide
oxidizing agent,3% soln used to treat some wound infections, particularly deep wounds that contain anaerobes. (eg in gingiva) axn is somewhat antagonized by catalase containing cells/tissues/bacteria
Potassium permanganate is used as what kind of antiseptic
in dilute soln
another oxidizing agent
used as an urethral antiseptic
antiseptic axn of phenols
effectively denatures proteins, therefore kills a wide variety of bacteria, but requires high concentrations
ordinary soap
anionic detergents, only weakly bacteriocidal, mostly just move bacteria around
antibacterial soaps include this antibacterial agent
TRICLOSAN (INHIBITS a specific step in LIPID BIOSYNTEHSIS) resistant mutants can be isolated
how is silver nitrate (1%) used to treat newborns?
drop placed in eyes, kills gonococcal organisms.
mercurial compounds in organic form, commonly used on minor skin wounds, how do these heavy metals work as antiseptic agents?
heavy metals bind to SH groups in protein
formaldehyde is often used in what?
glutaraldehyde is sometimes used to treat areas where...
blood samples and used syringes are present and may be contaminated with hep. virus.
cidex is a buffered 2% soln of:
sometimes used to treat areas where...
blood samples and used syringes are present and may be contaminated with hep. virus.
Preservatives used in food
short chain fatty acids and organic acids. examples: lactic acid, propionic acid, benzoic acid, natural phenolics