chapter 12 antimicrobial treatment
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61 Terms
1, infectious, 5, disabilities, tuberculosis
principles of antimicrobial therapy
in the early 1900s, …. out of 3 children were expected to die of an … disease before the age of …
those that survived had lifelong … upon recovery
common causes of death:
…
diphtheria
scarlet fever
meningitis
expectancy, quality, salvarsan, syphilis, narrow, miracle, basis, broad
principles of antimicrobial therapy
the advent of antibiotics drastically increased life … and … of life
… was the 1st antibiotic discovered in 1910
only effective against …. so it did not gain as much fame as penicillin
…. spectrum antibiotic
penicillin was discovered in 1928
touted as a …. drug and was used as the … of 25 different drugs
… spectrum antibiotic
slowing, speeds
principles of antimicrobial therapy
but antibiotic discoveries are … down as resistance …
infective, without, host
principles of antimicrobial therapy
the goal of antimicrobial therapy is to destroy the … agent …. harming the … cells
microbe, host, microbicidal, soluble, bodily, potent, broken, excreted, slow, no, complements, assists, tissues, fluids, easy, site, allergies, predispose, infections
principles of antimicrobial therapy
ideal antimicrobial drug characteristics
toxic to … but not …
…. rather than microbistatic
….. in …. fluids
…. for a long enough period of time without being … down or …
… or … antimicrobial resistance
… or .. host defenses
active in … and bodily ….
… to deliver to … of infection
does not cause … or … host to other ….
prevent infection, risk
the origins of antimicrobial drugs
prophylaxis - a drug used to … .. of a person at ….
drug, microbe
the origins of antimicrobial drugs
antimicrobial - a term used for any …., regardless of the type of … it targets
control infection, antibiotics, semi, synthetic
the origins of antimicrobial drugs
antimicrobial chemotherapy
the use of drugs to … …
….
….synthetic drugs
…. drugs
naturally, some, inhibit, destroy growth
the origins of antimicrobial drugs
antibiotics
substances produced … by some microbes that can … or .. .. of other microbes
chemically, isolated, natural
the origins of antimicrobial drugs
semisynthetic - drugs that are … modified after being … from … sources
chemical, lab
the origins of antimicrobial drugs
synthetic - drugs that are produced entirely by … reactions in the …
identity, degree, susceptibility, medical, patient
starting treatment
things to consider prior to starting a treatment
the … of the microbe causing infection
the … of the microbes .. to drugs
the … condition of the …
identify, susceptibility, treat
identifying the infection
the ideal process of treating with antibiotics
.. the infectious agent
determine …
….
direct, fluids, characteristic
identifying the infection
the infectious agent must first be identified
done through … examination of bodily …
sometimes symptoms are …. enough
kirby, bauer, tube dilution
testing to see which drug will work
the drug susceptibility of the infectious agent must be determined
the … - … technique
… .. test
which, surface, special, discs, premeasured, antibiotics, zone of inhibition, incubation, standard, sensitivity
testing to see which drug will work
the kirby-bauer technique
identifies … drug should be used
the .. of a plate of .. medium is spread with test bacterium
small .. containing .. amounts of … are dispensed onto the bacterial lawn
a .. .. .. formed during … is measured and compared with a … for each drug
antibiogram - profile of antimicrobial ….
much, smallest, highest, visibly inhibits, smallest, dosage, automated machinery
testing to see which drug will work
tube dilution method
identifies how … drug should be used
minimum inhibitory concentration (MIC) - the …. concentration (… dilution) of drug that … … growth
useful in determining the … effective … of a drug
in clinical labs, these tests are performed by .. …
safe, dose, dose, toxic, minimum, therapeutic, closer, smaller, greater, toxic, highest, widest, safety
testing to see which drug will work
therapeutic index
how … is this drug at this ….?
the ratio of the … of the drug that is .. to humans to its .. effective (…) dose
the … these 2 figures are to each other (the .. the ratio), the .. potential for .. drug reactions
when drugs have similar MICs, the drug with the … TI (therapeutic index) has the .. margin of …..
inability, diffuse, body, resistant, sample, more, mixed, resistant, preexisting, activity, response, allergy, liver, kidney, infants, elderly, pregnant
testing to see which drug will work
treatment can fail for various reasons
the … of the drug to .. into that … compartment (brain, joints, skin)
… microbes in the infection that didn’t make it into the … collected for testing
an infection caused by … than one pathogen (…), some of which are … to the drug
patient history must be considered
… medical conditions that will influence the .. of the drug or the … of the patient
history of .. to a certain class of drugs
underlying .. or … disease
…., …., and … women require special precautions
treatment, kill, inhibit, without, host, cell wall, block, actions, synthesis, microorganisms, vertebrate, structures, host, microbe, cell membrane, similar, difficult
affecting microbes, affecting humans
selective toxicity
central concept in antibiotic ….
antimicrobial drugs should … or .. microbial cells … simultaneously damaging … tissues
… .. because humans don’t have peptidoglycan
the best drugs in current use … the .. or .. of molecules in … but not … cells
the worst drugs act on … in both the … and …. (ex. … …)
as characteristics of the infectious agent becomes more .. to the host, it becomes more … to treat without severe side effects
bactericidal, rigid pg, rupture, active, pg, transport, envelope, one, more, enzymes, weak, growth, osmotically, inhibits, pg subunits, hinders, elongation, peptidases, cross link, glycan, completion, wall
mechanisms of drug action on microbes
cell wall synthesis - ….
cells of most bacteria contain a .. … layer that protects the cell from …
active cells must constantly make .. and … it to its proper place in the cell …
antimicrobials react with … or … of the … needed to do this
this makes the cell develop … points at .. sites and become … fragile
… the formation of the basic .. ..
… pg …
bind and block … that .. .. the .. molecules and interrupt the …. of the cell ….
bactericidal, damaged, dies, metabolism, lysis, not, dividing, lipids, not, host, surface, proteins, nitrogen bases, sterols, leakage, human, toxicity
mechanisms of drug action on microbes
cell membrane disruption - …
a cell with a … membrane eventually .. from disruption in … or .. and does … have to be …. to be destroyed
antibiotic classes that damage cell membranes select for specific … found in microbial cell membranes but … in those of the host
distorts the cell …..
leakage of … and .. …
forms complexes with .. in the membrane
…
can affect .. cell membrane (..)
bactericidal, translation, synthesis, ribosome, mrna, size, structure, mitochondrial, prokaryotic, damaged, 30S, misreads, 50S, peptide
mechanisms of drug action on microbes
protein synthesis - ….
most inhibitors of …, or protein …, react with the .. - … complex
although human cells have ribosomes, the ribosomes of eukaryotes are different in … and … than prokaryotic ribosomes
problem: … dna in the euaryotic cells resembles … dna so it can be … by these drugs
binds the … ribosomes
…. mrna
binds to the … ribosomes
prevents … bond
nucleotides, replication, transcription, translation, folic, building, dna, cross, double, gyrase, purines, pyrimidines, replication
mechanisms of drug action on microbes
nucleic acid synthesis inhibitors
antimicrobial drugs interfere with nucleic acid synthesis by blocking synthesis of …, inhibiting …, or stopping … (this will inhibit the … process too)
inhibit … acid synthesis (used as a … block of …)
binds and … - links the …. helix
analogs of … and …. insert in the viral nucleic acid and block further ….
bactericidal, chrysogenum, major, wall synthesis, sensitive gr+, streptococci, gr-, meningococci, spyrochete, penicillinase, beta lactamases, structure
survey of major antimicrobial drug groups
penicillin group of B-lactams - …..
penicillin … is the … source
works by inhibiting cell … …
drug of choice for .. .. (most …) and … (… and the syphilis ….)
resistant bacteria have …. or … … to destroy the … of penicillin
natural, important, semisynthetic, broader, gr- enteric rods, penicillinase resistant
survey of major antimicrobial drug groups
penicillin group of B-lactams
a diverse group (1st, 2nd, 3rd) generations
… (pencillin G and V) are the most important forms
…. (amoxicillin) have … spectra and can treat … … …
… … penicillins (methicillin)
wall, ring, chemically, penicillins, resistant, penicillinases, root cef, ceph, kef
survey of major antimicrobial drug groups
cephalosporin group of B-lactams
target cell …
isolated in the 1940s by cephalosporium acremonium
beta lactam … that can be … altered
similar mode of action to …. but … to most …
generic names have .. …, …., or …
glycopeptide, staph, resistant, wall, toxic, orientalis
survey of major antimicrobial drug groups
… - vancomycin
treats … if methicillin and penicillin …
targets cell …
very …
source amycolatopsis ….
cyclic polypeptide, narrow, subtilis, wall, neosporin
survey of major antimicrobial drug groups
.. .. - bacitracin
… spectrum
source is bacillus …
targets cell ….
found in … (along with neomycin)
protein synthesis, one, more, sugars, aminocyclitol ring, streptomyces, broad
survey of major antimicrobial drug groups
aminoglycoside drugs
inhibit .. ..
composed of … or .. amino … and an … …
products of ….
… antimicrobial spectrum
semisynthetic, protein, broad, low, sexually, glycylcyclines
survey of major antimicrobial drug groups
tetracycline drugs
… drugs that inhibit …. synthesis
… spectrum and … cost
commonly used to treat …. transmitted diseases
…. are new derivatives of tetracyclines
macrolide, broad, prophylatic, surgery, protein, pneumonia, acne
survey of major antimicrobial drug groups
… drugs - erythromycin
… spectrum
commonly used as … drug prior to ….
inhibits …. synthesis
treats mycoplasma …., chlamydia, ….
gi, limits, respiratory, resistant
survey of major antimicrobial drug groups
macrolide drugs
clindamycin
adverse reactions in the … tract .. its use
telithromycin
… tract infections suspected to be caused by … microbes
folic, analogs, chemical, another, compete, site, enzyme, folate, prevents, dna, rna, amino, selectively toxic, diet, enzyme, not, humans
survey of major antimicrobial drug groups
sulfonamide drugs
inhibit … acid synthesis
.. (a … that closely resembles …)
competitive inhibition: … for the … on the enzyme where … would bind. this …. folic acid synthesis which is needed to make …, …, and … acids
this is … … because mammals get folic acid from the …, not by .. reactions. so this enzyme is … present in …
first modern, synthetic, not, bacteria, fungi
survey of major antimicrobial drug groups
sulfonamide drugs
.. .. antimicrobial drugs
…: do .. originate from … or …
synthetic, folic, synergistic, pneumonia, aids
survey of major antimicrobial drug groups
trimethoprim/bactrim
…..
targets .. acid synthesis
used together with sulfa (..) to treat pneumocystic … in … patients
broad, tb, antimalarial, cross, double, anthrax, gyrase, purines, pyrimidines, replication
survey of major antimicrobial drug groups
nucleic acid synthesis inhibitors
fluoroquinolone - … spectrum that is used to treat …
chloroquine (…) - binds and .. - links the .. helix
ciprofloxacin - 2001 … attack
naladixic - inhibits …
asidothymidine (AZT) - analogs of .. and … insert in the viral nucleic acid and block further ….
polymyxa, kidney
survey of major antimicrobial drug groups
cell membrane inhibitors
polmyxins
derived from bacillus …
toxic to the ….
antifungal, humans, skin, membrane, permeability, sterol, ergosterol, humans
survey of major antimicrobial drug groups
cell membrane inhibitors
polyenes
….
some toxicity to …
commonly used for .. infections
targets the … - loss of selective ..
attack membrane ….
… not found in ….
antimalarial, principal, less, amoebicide, pyrantel
survey of major antimicrobial drug groups
antiprotozoal and antihelminthic drugs
…. drugs
quinine: .. treatment for hundreds of years
replaced by chloroquine and primaquine: … toxicity
chemotherapy for other protozoan infections
metronidazole: …
antihelminthic drug therapy
…
limited, host, metabolism, stop, stop, selective, replication, penetration, transcription, translation, assembly, release, artifical
survey of major antimicrobial drug groups
antiviral drugs
…. drugs available
problem: virus uses …. cell for …, so if you … viral metabolism, you also … host metabolism
difficult to main … toxicity
effective drugs - target viral … cycle
stop … of virus into host cell
block … and … of viral molecules
block …. / … of virus
interferon - … antiviral drug
adaptive, tolerate, inhibitory, versatility, adaptability, populations, resistant, produce, resistance, previously
antimicrobial resistance
drug resistance
…. response in which microorganisms begin to … an amount of drug that would ordinarily be …
due to the genetic … and … of microbial …
intrinsic vs acquired resistance
intrinsic - bacteria must be .. to any antibiotic that they themselves ….
acquired - bacterial … to a drug that they were …. sensitive
spontaneous, minimal, advantageous, conjugation, transformation, transduction, duplicated, one, another, plasmid, chromosome, biofilm
antimicrobial resistance
causes of drug resistance
….. mutation
… chance that the mutation will be …
horizontal transfer
resistance (R) factors - plasmids that are transferred through …, …., or ….
transposable drug resistance sequences (transposons) - … and inserted from .. plasmid to … or from the … to the ….
… colonization
smaller, resistance, large, populations, constant, do
antimicrobial resistance
spontaneous mutation
…. chance that the mutation will confer drug …..
… microbial … and …. rate of mutation ensures that such mutations … occur
sharing, rapid, resistant, frequent, unrelated, biota, environment
antimicrobial resistance
horizontal transfer
… of resistance genes accounts for the … proliferation of drug … species
gene transfer are extremely … in nature
genes from … bacteria, viruses, and other organisms live in the body’s normal …. and ….
less sensitive, same, phenotypes, quorum sensing, dnase, antibiotcs, pretreatment
antimicrobial resistance
biofilm colonization
1,000 times … … to the same …
different … are expressed by biofilm bacteria
treatment of biofilms
interrupting .. .. pathways
adding … to ….
….
fail, surface, protected phenotypic, depletion, waste, accumulation, anatagonized
antimicrobial resistance
biofilm colonization
slow penetration
antibiotic may … to penetrate beyond the … layers of the biofilm
resistant phenotype
some of the bacteria may differentiate into a .. … state
altered microenvironment
in zones of nutrient … or … product …, antibiotic action may be ….
large, naturally, resistant, not, low, exposed, sensitive, killed, remain
interactions between microbes and drugs
any … population of microbes is likely to contain a few individual cells that are .. drug …
if the drug is .. present in the population, the number of these resistant forms will remain ..
if the population is … to the drug, … individuals will be … and the resistant forms will ….
offspring, resistant, replacement, preponderance, resistant
interactions between microbes and drugs
as the population exposed to the antibiotic proliferates
…. of … microbes will inherit drug resistant genes
the … population will have a … of drug resistant forms
eventually the population will becomes ….
throat, sinus, lung, respiratory, viral, not, antibacterial, shotgun, exported
the human role in antimicrobial resistance
75% of antimicrobial prescriptions are for …., …., …., and upper …. infections, the majority of which are likely … and will … benefit from … drugs
the … approach to antimicrobial therapy
tons of excess antimicrobial drugs produced in the united states are …. to other countries
susceptible, weakened, universal, penicillin
the human role in antimicrobial resistance
the hospital environment continually exposes pathogens to a variety of drugs
hospitals houses … patients with … defenses
workforce may not strictly adhere to …. precautions
this has led to … resistance in nearly 100% of all staphylococcus aureus strains in 30 years
livestock, decreases, health, size, enteric, selected, amplified, drugs, jump, humans, resistant
the human role in antimicrobial resistance
nearly 80% of all antibiotics in the United States are given to ….
allegedly …. infections and improves animal … and ….
…. bacteria share resistance plasmids that are constantly …. and … by exposure to …
these pathogens … to … and cause drug … infections
travel, food, rapid
the human role in antimicrobial resistance
global .. and globalization of .. products allows … export of drug resistance
new, custom, disabling host, phage, wound, specific, one, normal, reactive oxygen, deliver, shut, expression
new approaches to antimicrobial therapies
past approach
finding … targets in the bacterial cell
… designing drugs that aim for these new targets
novel approach
…. … molecules that the invaders use to enhance their position
low tech solutions
incorporating .. into .. dressings
phage are extremely … and only infect … species of bacteria, leaving … microbiota alone
nanomaterials
create … … species or … antibiotcs
antisense rnas
… down … of genes
live, intestinal, replace, lost, augment, allergies, nutrients, growth, beneficial, intestine
new approaches to antimicrobial therapies
probiotics
preparations of … microorganisms fed to animals and humans to improve …. biota
… microbes … during antimicrobial therapy
… the biota already there
safe, effective, useful in treating food …
prebiotics
…. that encourage the .. of … microbes in the …
c diff, feces, beneficial, healthy, affected, colonoscopy
new approaches to antimicrobial therapies
fecal transplants
treatment for recurring … … infections
involves the transfer of …, containing … normal biota, from … to …. patients via …
direct, tissues, toxicity, allergies, balance, normal
interactions between drug and host
categories of major side effects of drugs
… damage to … through …
…. reactions
disruption in the … of … microbial biota
enamel, permanent, discoloration, liver, pregnant, placenta, fetal bones, teeth
interactions between drug and host
direct damage to tissues through toxicity
tetracyclines - bind to the … of teeth, causing a … gray to brown …
cause … damage in … women
cross the … and are deposited in … … and …
antigen, allergic, intact, metabolic alteration
interactions between drug and host
allergic reactions - drug acts as an .. that stimulates the … response
can be provoked by the … drug molecule or substances that develop from the body’s .. … of the drug
common, oral, severe intestinal, colitis, directly, lining
interactions between drug and host
disruptions in the balance of normal microbial biota - diarrhea
most … complaint associated with … antimicrobial therapy
can progress to … … irritation or ….
some drugs … irritate the intestinal ….
infections, destroys, original, beneficial, destroyed, therapy, small, overgrow, disease
interactions between drug and host
introduction of a broad spectrum antimicrobial
treats …
…. normal biota, even those far removed from the …. infection
superinfection
… resident species are …. through antibiotic …
microbes once …. in number begin to … and cause …..